diff --git a/.gitmodules b/.gitmodules index 974a62fae..e62836a80 100644 --- a/.gitmodules +++ b/.gitmodules @@ -33,3 +33,6 @@ [submodule "3rdparty/kseqpp"] path = 3rdparty/kseqpp url = https://github.com/cartoonist/kseqpp.git +[submodule "3rdparty/htslib"] + path = 3rdparty/htslib + url = https://github.com/samtools/htslib.git diff --git a/3rdparty/htslib b/3rdparty/htslib new file mode 160000 index 000000000..a79009b38 --- /dev/null +++ b/3rdparty/htslib @@ -0,0 +1 @@ +Subproject commit a79009b38ce83e39bcbc8f54c00cf203621aa5bb diff --git a/CMakeLists.txt b/CMakeLists.txt index 786714ee0..414c78dfd 100644 --- a/CMakeLists.txt +++ b/CMakeLists.txt @@ -23,8 +23,8 @@ string(STRIP ${GW_VERSION} GW_VERSION) project(${GW_PROJECT_NAME}) # Process options. -option(gw_enable_tests "Build GenomeWorks unit tests" OFF) -option(gw_enable_benchmarks "Build GenomeWorks benchmarks" OFF) +option(gw_enable_tests "Build GenomeWorks unit tests" ON) +option(gw_enable_benchmarks "Build GenomeWorks benchmarks" ON) option(gw_build_shared "Build GenomeWorks libraries as shared objects" OFF) option(gw_device_synchronize_kernels "Run cudaDeviceSynchronize() in GW_CU_CHECK_ERR calls" OFF) option(gw_optimize_for_native_cpu "Build with march=native" ON) @@ -40,7 +40,9 @@ option(gw_enable_cudapoa_nw_print "Enable verbose prints within cudapoa NW kerne option(gw_profiling "Compile a binary for profiling with NVTX markers." OFF) option(gw_enable_caching_allocator "Enable caching allocator." ON) option(gw_generate_docs "Generate Doxygen documentation" ON) -option(gw_cuda_gen_all_arch "ON: Generate optimized CUDA code for all architectures | OFF: for detected architectures only" ON) +option(gw_cuda_gen_all_arch "ON: Generate optimized CUDA code for all architectures | OFF: for detected architectures only" OFF) +# Optionally build htslib for SAM/BAM support. Requires autoconf to be installed +option(gw_build_htslib "Build 3rdparty htslib that allows output in SAM/BAM format" ON) # Must be included before others for options value validation include(cmake/Utils.cmake) @@ -83,6 +85,7 @@ add_subdirectory(common/io) add_subdirectory(cudapoa) add_subdirectory(cudamapper) add_subdirectory(cudaaligner) +add_subdirectory(cudaextender) # Add documentation generation. validate_boolean(gw_generate_docs) diff --git a/README.md b/README.md index 6d751551c..ddb141636 100644 --- a/README.md +++ b/README.md @@ -6,9 +6,10 @@ GenomeWorks is a GPU-accelerated library for biological sequence analysis. This For more detailed API documentation please refer to the [documentation](#enable-doc-generation). * Modules - * [cudamapper](#cudamapper) - CUDA-accelerated sequence to sequence mapping - * [cudapoa](#cudapoa) - CUDA-accelerated partial order alignment - * [cudaaligner](#cudaaligner) - CUDA-accelerated pairwise sequence alignment + * [cudamapper](cudamapper/README.md) - CUDA-accelerated sequence to sequence mapping + * [cudapoa](cudapoa/README.md) - CUDA-accelerated partial order alignment + * [cudaaligner](cudaaligner/README.md) - CUDA-accelerated pairwise sequence alignment + * [cudaextender](cudaextender/README.md) - CUDA-accelerated seed extension * Setup GenomeWorks * [Clone GenomeWorks](#clone-genomeworks) * [System Requirements](#system-requirements) @@ -16,71 +17,6 @@ For more detailed API documentation please refer to the [documentation](#enable- * [Python API](#genomeworks-python-api) * [Development Support](#development-support) -### cudamapper - -The `cudamapper` package provides minimizer-based GPU-accelerated approximate mapping. - -#### Tool - *cudamapper* - -`cudamapper` is an end-to-end command line to for sequence to sequence mapping. `cudamapper` outputs -mappings in the PAF format and is currently optimised for all-vs-all long read (ONT, Pacific Biosciences) sequences. - -To run all-vs all overlaps use the following command: - -`cudamapper in.fasta in.fasta` - -A query fasta can be mapped to a reference as follows: - -`cudamapper query.fasta target.fasta` - -To access more information about running cudamapper, run `cudamapper --help`. - -#### Library - *libcudamapper.so* - -* `Indexer` module to generate an index of minimizers from a list of sequences. -* `Matcher` module to find locations of matching pairs of minimizers between sequences using minimizer indices. -* `Overlapper` module to generate overlaps from sequence of minimizer matches generated by matcher. - -#### Sample - *sample_cudamapper* - -A prototypical binary highlighting the usage of `libcudamapper.so` APIs (indexer, matcher and overlapper) and -techniques to tie them into an application. - -### cudapoa - -The `cudapoa` package provides a GPU-accelerated implementation of the [Partial Order Alignment](https://simpsonlab.github.io/2015/05/01/understanding-poa/) -algorithm. It is heavily influenced by [SPOA](https://github.com/rvaser/spoa) and in many cases can be considered a GPU-accelerated replacement. Features include: - -#### Tool - *cudapoa* - -A command line tool for generating consensus and MSA from a list of `fasta`/`fastq` files. The tool -is built on top of `libcudapoa.so` and showcases optimization strategies for writing high performance -applications with `libcudapoa.so`. - -#### Library - *libcudapoa.so* - -* Generation of consensus sequences -* Generation of multi-sequence alignments (MSAs) -* Custom adaptive band implementation of POA -* Support for long and short read sequences - -#### Sample - *sample_cudapoa* - -A prototypical binary to showcase the use of `libcudapoa.so` APIs. - -### cudaaligner - -The `cudaaligner` package provides GPU-accelerated global alignment. Features include: - -#### Library - *libcudaaligner.so* - -* Short and long read support -* Banded implementation with configurable band width for flexible performance and accuracy trade-off - -#### Sample - *sample_cudaaligner* - -A prototypical binary to showcase the use of `libcudaaligner.so` APIs. - ## Clone GenomeWorks ### Latest released version @@ -104,9 +40,12 @@ Minimum requirements - 1. Ubuntu 16.04 or Ubuntu 18.04 2. CUDA 9.0+ (official instructions for installing CUDA are available [here](https://docs.nvidia.com/cuda/cuda-installation-guide-linux/index.html)) -3. gcc/g++ 5.4.0+ -4. Python 3.6.7+ -5. CMake (>= 3.0) +3. GPU generation Pascal and later (compute capability >= 6.0) +4. gcc/g++ 5.4.0+ / 7.x.x +5. Python 3.6.7+ +6. CMake (>= 3.10.2) +7. autoconf (required to output SAM/BAM files) +8. automake (required to output SAM/BAM files) ## GenomeWorks Setup @@ -124,6 +63,8 @@ NOTE : The `gw_cuda_gen_all_arch=OFF` option pre-generates optimized code only f For building a binary that pre-generates opimized code for all common GPU architectures, please remove the option or set it to `ON`. +NOTE : (OPTIONAL) To enable outputting overlaps in SAM/BAM format, pass the `gw_build_htslib=ON` option. + ### Package generation Package generation puts the libraries, headers and binaries built by the `make` command above into a `.deb`/`.rpm` for portability and easy installation. The package generation itself doesn't diff --git a/VERSION b/VERSION index a918a2aa1..009695bfc 100644 --- a/VERSION +++ b/VERSION @@ -1 +1,2 @@ 0.6.0 + diff --git a/ci/checks/check_copyright.py b/ci/checks/check_copyright.py index ef58d3dc5..458be5b34 100755 --- a/ci/checks/check_copyright.py +++ b/ci/checks/check_copyright.py @@ -145,7 +145,7 @@ def copyright_present(f): f - Path to file """ with io.open(f, "r", encoding="utf-8") as fh: - return re.search('Copyright 20[0-9]+-20[0-9]+', fh.read()) + return re.search('Copyright (20[0-9][0-9]-)?20[0-9][0-9] NVIDIA CORPORATION', fh.read()) def parse_args(): diff --git a/ci/common/build-test-sdk.sh b/ci/common/build-test-sdk.sh index 216c9746f..6574882a6 100644 --- a/ci/common/build-test-sdk.sh +++ b/ci/common/build-test-sdk.sh @@ -31,6 +31,8 @@ cmake .. "${CMAKE_COMMON_VARIABLES[@]}" \ -Dgw_enable_tests=ON \ -Dgw_enable_benchmarks=ON \ -Dgw_build_shared=ON \ + -Dgw_cuda_gen_all_arch=ON \ + -Dgw_build_htslib=ON \ -DCMAKE_INSTALL_PREFIX="${LOCAL_BUILD_DIR}/install" \ -GNinja diff --git a/ci/common/prep-init-env.sh b/ci/common/prep-init-env.sh index 378457abe..fcd06803c 100644 --- a/ci/common/prep-init-env.sh +++ b/ci/common/prep-init-env.sh @@ -53,8 +53,19 @@ python --version logger "Conda install GenomeWorks custom packages - clang-format" conda install --override-channels -c sarcasm clang-format -logger "Conda install GenomeWorks custom packages - doxygen ninja cmake" -conda install --override-channels -c conda-forge doxygen ninja cmake">=3.10.2" +logger "Conda install GenomeWorks custom packages - doxygen ninja" +conda install --override-channels -c conda-forge doxygen ninja + +# Building cudamapper, using CUDA_SELECT_NVCC_ARCH_FLAGS() with the 'common' argument, generates +# the "-gencode;arch=compute_72,code=sm_72" arch flag which is incompatible with CUDA 9.0 and causes nvcc command to fail +# Using cmake with a version older than 3.18 does not create 'compute_72' arch. +if [ "$(echo ${CUDA_VERSION} | cut -d"." -f1-2)" = "9.0" ]; then + logger "Conda install cmake for CUDA 9.0" + conda install --override-channels -c conda-forge cmake"=3.17" +else + logger "Conda install cmake" + conda install --override-channels -c conda-forge cmake">=3.10.2" +fi logger "Update LD_LIBRARY_PATH" export LD_LIBRARY_PATH=$LD_LIBRARY_PATH:/usr/local/lib diff --git a/ci/cpu/prebuild.sh b/ci/cpu/prebuild.sh index 912845ef9..bd26f5f00 100755 --- a/ci/cpu/prebuild.sh +++ b/ci/cpu/prebuild.sh @@ -22,4 +22,4 @@ # Note we still _BUILD_ for GPU, we just don't (can't) test on it export BUILD_FOR_GPU=1 export TEST_ON_GPU=0 -export CONDA_ENV_NAME="gdf" +export CONDA_ENV_NAME="parabricks" diff --git a/ci/gpu/prebuild.sh b/ci/gpu/prebuild.sh index 9ce52e560..606a33e3b 100644 --- a/ci/gpu/prebuild.sh +++ b/ci/gpu/prebuild.sh @@ -21,4 +21,4 @@ export BUILD_FOR_GPU=1 export TEST_ON_GPU=1 -export CONDA_ENV_NAME="gdf" +export CONDA_ENV_NAME="parabricks" diff --git a/cmake/3rdparty.cmake b/cmake/3rdparty.cmake index fbe90b1e2..f26ce2af5 100644 --- a/cmake/3rdparty.cmake +++ b/cmake/3rdparty.cmake @@ -50,3 +50,10 @@ set_property(TARGET cub APPEND PROPERTY INTERFACE_INCLUDE_DIRECTORIES "${CUB_DIR set(KSEQPP_DIR ${PROJECT_SOURCE_DIR}/3rdparty/kseqpp/src CACHE STRING "Path to kseqpp repo") + +if (gw_build_htslib) + include(cmake/BuildHTSLib.cmake) + build_htslib_source() +else() + message(STATUS "Not building htslib, overlap output to SAM & BAM unavailable. Enable with -Dgw_build_htslib=ON") +endif() diff --git a/cmake/BuildHTSLib.cmake b/cmake/BuildHTSLib.cmake new file mode 100644 index 000000000..e8dc02201 --- /dev/null +++ b/cmake/BuildHTSLib.cmake @@ -0,0 +1,42 @@ +# +# Copyright 2019-2020 NVIDIA CORPORATION. +# +# Licensed under the Apache License, Version 2.0 (the "License"); +# you may not use this file except in compliance with the License. +# You may obtain a copy of the License at +# +# http://www.apache.org/licenses/LICENSE-2.0 +# +# Unless required by applicable law or agreed to in writing, software +# distributed under the License is distributed on an "AS IS" BASIS, +# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +# See the License for the specific language governing permissions and +# limitations under the License. +# + +function(build_htslib_source) + message(STATUS "Building htslib") + set(HTSLIB_DIR ${PROJECT_SOURCE_DIR}/3rdparty/htslib/ CACHE STRING + "Path to htslib repo") + set(MAKE_COMMAND make) + set(HTSLIB_INSTALL ${MAKE_COMMAND} install prefix=${CMAKE_BINARY_DIR}/3rdparty/htslib) + set(htslib_PREFIX ${CMAKE_BINARY_DIR}/3rdparty/htslib) + include(ExternalProject) + ExternalProject_Add(htslib_project + PREFIX ${htslib_PREFIX} + SOURCE_DIR ${PROJECT_SOURCE_DIR}/3rdparty/htslib + BUILD_IN_SOURCE 1 + CONFIGURE_COMMAND autoheader && autoconf && ${HTSLIB_DIR}configure --disable-bz2 --disable-lzma --disable-libcurl --disable-s3 --disable-gcs + BUILD_COMMAND "${HTSLIB_INSTALL}" + INSTALL_COMMAND "" + BUILD_BYPRODUCTS ${CMAKE_BINARY_DIR}/3rdparty/htslib/lib/libhts.a + LOG_CONFIGURE 0 + LOG_BUILD 0 + LOG_TEST 0 + LOG_INSTALL 0 + ) + + include_directories(${CMAKE_BINARY_DIR}/3rdparty/htslib/include/htslib) + add_library(htslib STATIC IMPORTED) + set_property(TARGET htslib APPEND PROPERTY IMPORTED_LOCATION ${CMAKE_BINARY_DIR}/3rdparty/htslib/lib/libhts.a) +endfunction() diff --git a/common/base/CMakeLists.txt b/common/base/CMakeLists.txt index f301c375c..f0e6ac51c 100644 --- a/common/base/CMakeLists.txt +++ b/common/base/CMakeLists.txt @@ -26,7 +26,9 @@ message(STATUS "nvcc flags for ${MODULE_NAME}: ${CUDA_NVCC_FLAGS}") get_property(gw_library_type GLOBAL PROPERTY gw_library_type) add_library(${MODULE_NAME} ${gw_library_type} src/cudautils.cpp - src/logging.cpp) + src/logging.cpp + src/graph.cpp + ) target_link_libraries(${MODULE_NAME} PUBLIC spdlog ${CUDA_LIBRARIES}) if (gw_profiling) diff --git a/common/base/include/claraparabricks/genomeworks/logging/logging.hpp b/common/base/include/claraparabricks/genomeworks/logging/logging.hpp index d4e2ac777..962ca2325 100644 --- a/common/base/include/claraparabricks/genomeworks/logging/logging.hpp +++ b/common/base/include/claraparabricks/genomeworks/logging/logging.hpp @@ -95,6 +95,10 @@ // Due to a header file incompatibility with nvcc in CUDA 9.0 // logging through the logger class in GW is disabled for any .cu files. #pragma message("Logging disabled for CUDA Toolkit < 9.2") +#elif __GNUC__ >= 9 +// Due to a ISO C++ standard incompatibility the spdlog fails to pass +// pedantic requirements. +#pragma message("Logging disabled for GCC >= 9") #else #include #endif @@ -137,6 +141,8 @@ LoggingStatus SetHeader(bool logTime, bool logLocation); /// parameters as per https://github.com/gabime/spdlog/blob/v1.x/README.md #ifdef GW_CUDA_BEFORE_9_2 #define GW_LOG_DEBUG(...) +#elif __GNUC__ >= 9 +#define GW_LOG_DEBUG(...) #else #define GW_LOG_DEBUG(...) SPDLOG_DEBUG(__VA_ARGS__) #endif @@ -148,6 +154,8 @@ LoggingStatus SetHeader(bool logTime, bool logLocation); /// parameters as per https://github.com/gabime/spdlog/blob/v1.x/README.md #ifdef GW_CUDA_BEFORE_9_2 #define GW_LOG_INFO(...) +#elif __GNUC__ >= 9 +#define GW_LOG_INFO(...) #else #define GW_LOG_INFO(...) SPDLOG_INFO(__VA_ARGS__) #endif @@ -159,6 +167,8 @@ LoggingStatus SetHeader(bool logTime, bool logLocation); /// parameters as per https://github.com/gabime/spdlog/blob/v1.x/README.md #ifdef GW_CUDA_BEFORE_9_2 #define GW_LOG_WARN(...) +#elif __GNUC__ >= 9 +#define GW_LOG_WARN(...) #else #define GW_LOG_WARN(...) SPDLOG_WARN(__VA_ARGS__) #endif @@ -170,6 +180,8 @@ LoggingStatus SetHeader(bool logTime, bool logLocation); /// parameters as per https://github.com/gabime/spdlog/blob/v1.x/README.md #ifdef GW_CUDA_BEFORE_9_2 #define GW_LOG_ERROR(...) +#elif __GNUC__ >= 9 +#define GW_LOG_ERROR(...) #else #define GW_LOG_ERROR(...) SPDLOG_ERROR(__VA_ARGS__) #endif @@ -181,6 +193,8 @@ LoggingStatus SetHeader(bool logTime, bool logLocation); /// parameters as per https://github.com/gabime/spdlog/blob/v1.x/README.md #ifdef GW_CUDA_BEFORE_9_2 #define GW_LOG_CRITICAL(...) +#elif __GNUC__ >= 9 +#define GW_LOG_CRITICAL(...) #else #define GW_LOG_CRITICAL(...) SPDLOG_CRITICAL(__VA_ARGS__) #endif diff --git a/common/base/include/claraparabricks/genomeworks/types.hpp b/common/base/include/claraparabricks/genomeworks/types.hpp index b61d7c0e6..469699be8 100644 --- a/common/base/include/claraparabricks/genomeworks/types.hpp +++ b/common/base/include/claraparabricks/genomeworks/types.hpp @@ -21,6 +21,7 @@ #if __cplusplus >= 201703 #include #include +#include #else #include #include @@ -45,8 +46,8 @@ using position_in_read_t = std::uint32_t; using number_of_basepairs_t = position_in_read_t; // TODO: Once minimal supported GCC version is moved to GCC 7.1 -// or higher, thegw_optional_t and gw_string_view_t aliases -// can be removed and std::optional and std::string_view can +// or higher, gw_optional_t, gw_string_view_t and gw_byte_t aliases +// can be removed and std::optional, std::string_view and std::byte can // be used directly instead #if __cplusplus >= 201703 template @@ -54,12 +55,14 @@ using gw_optional_t = std::optional; using gw_nullopt_t = std::nullopt_t; constexpr gw_nullopt_t gw_nullopt = std::nullopt; using gw_string_view_t = std::string_view; +using gw_byte_t = std::byte; #else template using gw_optional_t = std::experimental::optional; using gw_nullopt_t = std::experimental::nullopt_t; constexpr gw_nullopt_t gw_nullopt = std::experimental::nullopt; using gw_string_view_t = std::experimental::string_view; +using gw_byte_t = unsigned char; #endif } // namespace genomeworks diff --git a/common/base/include/claraparabricks/genomeworks/utils/allocator.hpp b/common/base/include/claraparabricks/genomeworks/utils/allocator.hpp index 4e5672815..a448f9022 100644 --- a/common/base/include/claraparabricks/genomeworks/utils/allocator.hpp +++ b/common/base/include/claraparabricks/genomeworks/utils/allocator.hpp @@ -44,7 +44,11 @@ class CudaMallocAllocator using pointer = T*; /// \brief default constructor - CudaMallocAllocator() = default; + /// \param default_stream if a call to allocate() does not specify any streams this stream will be used instead, ignored in this allocator + explicit CudaMallocAllocator(cudaStream_t default_stream = 0) + { + static_cast(default_stream); + } /// \brief copy constructor /// \param rhs input allocator @@ -114,7 +118,7 @@ class CudaMallocAllocator /// \return pointer to allocated memory /// \throw device_memory_allocation_exception if allocation was not successful pointer allocate(std::size_t n, - const std::vector& streams = {{0}}) + const std::vector& streams = {}) { static_cast(streams); void* ptr = nullptr; @@ -153,7 +157,7 @@ class CudaMallocAllocator /// \brief A simple caching allocator for device memory allocations /// \tparam T -/// \tparam MemoryResource resource that does actual allocation, e.g. cudautils::DevicePreallocatedAllocator +/// \tparam MemoryResource resource that does actual allocation, e.g. cudautils::details::DevicePreallocatedAllocator template class CachingDeviceAllocator { @@ -168,12 +172,18 @@ class CachingDeviceAllocator /// Constructs an invalid CachingDeviceAllocator to allow default-construction of containers. /// A container using this allocator needs obtain a non-default constructed CachingDeviceAllocator object before performing any allocations. /// This can be achieved through through container assignment for example. - CachingDeviceAllocator() = default; + CachingDeviceAllocator() + : default_stream_(0) + { + } /// \brief Constructor /// \param max_cached_bytes max bytes used by memory resource - CachingDeviceAllocator(size_t max_cached_bytes) + /// \param default_stream if a call to allocate() does not specify any streams this stream will be used instead + explicit CachingDeviceAllocator(size_t max_cached_bytes, + cudaStream_t default_stream = 0) : memory_resource_(std::make_shared(max_cached_bytes)) + , default_stream_(default_stream) { } @@ -188,6 +198,7 @@ class CachingDeviceAllocator template CachingDeviceAllocator(const CachingDeviceAllocator& rhs) : memory_resource_(rhs.memory_resource()) + , default_stream_(rhs.default_stream()) { } @@ -205,6 +216,7 @@ class CachingDeviceAllocator CachingDeviceAllocator& operator=(const CachingDeviceAllocator& rhs) { memory_resource_ = rhs.memory_resource(); + default_stream_ = rhs.default_stream(); return *this; } @@ -219,6 +231,7 @@ class CachingDeviceAllocator template CachingDeviceAllocator(CachingDeviceAllocator&& rhs) : memory_resource_(rhs.memory_resource()) + , default_stream_(rhs.default_stream()) { } @@ -236,6 +249,7 @@ class CachingDeviceAllocator CachingDeviceAllocator& operator=(CachingDeviceAllocator&& rhs) { memory_resource_ = rhs.memory_resource(); + default_stream_ = rhs.default_stream(); return *this; } @@ -244,22 +258,23 @@ class CachingDeviceAllocator /// \brief asynchronously allocates a device array with enough space for n elements of value_type /// \param n number of elements to allocate the array for - /// \param streams on deallocation this memory block is guaranteed to live at least until all previously scheduled work in these streams has finished, if no stream is specified default stream (0) is used + /// \param streams on deallocation this memory block is guaranteed to live at least until all previously scheduled work in these streams has finished, if no streams are specified default_stream from constructor are used, if no default_stream was specified in constructor default stream is used /// \return pointer to allocated memory /// \throw device_memory_allocation_exception if allocation was not successful pointer allocate(std::size_t n, - const std::vector& streams = {{0}}) + const std::vector& streams = {}) { - assert(!streams.empty()); - if (!memory_resource_) { GW_LOG_ERROR("{}\n", "ERROR:: Trying to allocate memory from an default-constructed CachingDeviceAllocator. Please assign a non-default-constructed CachingDeviceAllocator before performing any memory operations."); assert(false); std::abort(); } + void* ptr = nullptr; - cudaError_t err = memory_resource_->DeviceAllocate(&ptr, n * sizeof(T), streams); + cudaError_t err = memory_resource_->DeviceAllocate(&ptr, + n * sizeof(T), + streams.empty() ? std::vector(1, default_stream_) : streams); // if no streams have been specified use default_stream_ if (err == cudaErrorMemoryAllocation) { throw device_memory_allocation_exception(); @@ -295,12 +310,17 @@ class CachingDeviceAllocator /// \return a shared pointer to memory_resource std::shared_ptr memory_resource() const { return memory_resource_; } + /// \brief returns default stream + /// \return default stream + cudaStream_t default_stream() const { return default_stream_; } + private: std::shared_ptr memory_resource_; + cudaStream_t default_stream_; }; #ifdef GW_ENABLE_CACHING_ALLOCATOR -using DefaultDeviceAllocator = CachingDeviceAllocator; +using DefaultDeviceAllocator = CachingDeviceAllocator; #else using DefaultDeviceAllocator = CudaMallocAllocator; #endif @@ -323,12 +343,16 @@ inline int64_t get_size_of_largest_free_memory_block(DefaultDeviceAllocator cons /// Default constuction of CachingDeviceAllocator yields an dummy object /// which cannot allocate memory. /// \param max_cached_bytes max bytes used by memory resource used by CachingDeviceAllocator (default: 2GiB, unused for CudaMallocAllocator) -inline DefaultDeviceAllocator create_default_device_allocator(std::size_t max_caching_size = 2ull * 1024 * 1024 * 1024) +/// \param default_stream if a call to allocate() does not specify any streams this stream will be used instead (unused for CudaMallocAllocator) +inline DefaultDeviceAllocator create_default_device_allocator(std::size_t max_caching_size = 2ull * 1024 * 1024 * 1024, + cudaStream_t default_stream = 0) { #ifdef GW_ENABLE_CACHING_ALLOCATOR - return DefaultDeviceAllocator(max_caching_size); + return DefaultDeviceAllocator(max_caching_size, + default_stream); #else static_cast(max_caching_size); + static_cast(default_stream); return DefaultDeviceAllocator(); #endif } diff --git a/common/base/include/claraparabricks/genomeworks/utils/cudasort.cuh b/common/base/include/claraparabricks/genomeworks/utils/cudasort.cuh index a2ed4d4d1..94ac6b713 100644 --- a/common/base/include/claraparabricks/genomeworks/utils/cudasort.cuh +++ b/common/base/include/claraparabricks/genomeworks/utils/cudasort.cuh @@ -176,7 +176,7 @@ void sort_by_two_keys(device_buffer& more_significant_keys, device_buffer less_significant_key_sorted(number_of_elements, allocator, cuda_stream); device_buffer move_to_index_sorted(number_of_elements, allocator, cuda_stream); - device_buffer temp_storage_vect(0, allocator); + device_buffer temp_storage_vect(0, allocator, cuda_stream); details::perform_radix_sort(temp_storage_vect, less_significant_keys.data(), diff --git a/common/base/include/claraparabricks/genomeworks/utils/device_buffer.hpp b/common/base/include/claraparabricks/genomeworks/utils/device_buffer.hpp index 83c9a48f2..90d8a4db1 100644 --- a/common/base/include/claraparabricks/genomeworks/utils/device_buffer.hpp +++ b/common/base/include/claraparabricks/genomeworks/utils/device_buffer.hpp @@ -215,7 +215,7 @@ class buffer template #ifdef GW_ENABLE_CACHING_ALLOCATOR -using device_buffer = details::buffer>; +using device_buffer = details::buffer>; #else using device_buffer = details::buffer>; #endif diff --git a/common/base/include/claraparabricks/genomeworks/utils/device_preallocated_allocator.cuh b/common/base/include/claraparabricks/genomeworks/utils/device_preallocated_allocator.cuh index 9517c15b3..70b352164 100644 --- a/common/base/include/claraparabricks/genomeworks/utils/device_preallocated_allocator.cuh +++ b/common/base/include/claraparabricks/genomeworks/utils/device_preallocated_allocator.cuh @@ -23,6 +23,7 @@ #include #include +#include namespace claraparabricks { @@ -30,9 +31,12 @@ namespace claraparabricks namespace genomeworks { +namespace details +{ + /// \brief Allocator that preallocates one big buffer of device memory and assigns sections of it to allocation requests /// Allocator allocates one big buffer of device memory during constructor and keeps it until destruction. -/// For every allocation request it linearly scans the preallocated memory and assigns first buffer of it that is big enough. +/// For every allocation request it linearly scans the preallocated buffer and assigns first section of it that is big enough. /// /// For example imagine 100000 bytes buffer has been preallocated and that sections between (10000, 19999), (30000, 39999) /// and (60000, 79999) bytes have already been assigned: @@ -47,8 +51,8 @@ namespace genomeworks /// 0 --- 10000 --- 20000 --- 30000 --- 40000 ------ 55000 - 60000 --- 70000 --- 80000 --- 90000 --- 100000 /// | FREE | USED | FREE | USED | USED | FREE | USED | FREE | /// -/// Uppon returning a memory allocation its gets merged with any neighboring free arey, so if section (10000, 19999) is -/// returned the memory will look like this: +/// Upon deallocation deallocated memory gets merged with neighboring free blocks, if any, so if section (10000, 19999) is +/// deallocated the memory will look like this: /// /// 0 ---------------------- 30000 --- 40000 ------ 55000 - 60000 --- 70000 --- 80000 --- 90000 --- 100000 /// | FREE | USED | USED | FREE | USED | FREE | @@ -56,7 +60,7 @@ namespace genomeworks /// Allocator aligns memory by 256 bytes /// /// Note that this allocator heavily relies on iterating over lists of free and used memory and should thus -/// not be used for cases when there are millions of allocation at a time +/// not be used when there are many allocations and deallocations class DevicePreallocatedAllocator { public: @@ -65,12 +69,12 @@ public: /// \param buffer_size DevicePreallocatedAllocator(size_t buffer_size) : buffer_size_(buffer_size) - , buffer_ptr_(create_buffer(buffer_size)) + , buffer_ptr_(create_buffer(buffer_size_)) { - assert(buffer_size > 0); + assert(buffer_size_ > 0); MemoryBlock whole_memory_block; whole_memory_block.begin = 0; - whole_memory_block.size = buffer_size; + whole_memory_block.size = buffer_size_; free_blocks_.push_back(whole_memory_block); } @@ -105,7 +109,7 @@ public: /// \brief deallocates memory (returns its part of buffer to the list of free parts) /// This function blocks until all work on associated_stream is done /// \param ptr - /// \return error status + /// \return cudaSuccess if deallocation was successful, cudaErrorInvalidValue otherwise cudaError_t DeviceFree(void* ptr) { cudaError_t status = cudaSuccess; @@ -163,25 +167,15 @@ private: /// \param associated_streams on deallocation this memory block is guaranteed to live at least until all previously scheduled work in these streams has finished /// \return cudaSuccess if allocation was successful, cudaErrorMemoryAllocation otherwise cudaError_t allocate_memory_block(void** ptr, - size_t bytes_needed, + const size_t bytes_needed, const std::vector& associated_streams) { - *ptr = nullptr; - if (free_blocks_.empty()) { + *ptr = nullptr; return cudaErrorMemoryAllocation; } - // ** All allocations should be alligned with 256 bytes - // The easiest way to do this is to make all allocation request sizes divisible by 256 - if ((bytes_needed & 0xFF) != 0) - { - // bytes needed not divisible by 256, increase it to the next value divisible by 256 - bytes_needed = bytes_needed + (0x100 - (bytes_needed & 0xFF)); - } - assert((bytes_needed & 0xFF) == 0); - // ** look for first free block that can fit requested size auto block_to_get_memory_from_iter = std::find_if(std::begin(free_blocks_), std::end(free_blocks_), @@ -191,15 +185,21 @@ private: if (block_to_get_memory_from_iter == std::end(free_blocks_)) { + *ptr = nullptr; return cudaErrorMemoryAllocation; } + assert(!associated_streams.empty()); MemoryBlock new_memory_block{block_to_get_memory_from_iter->begin, bytes_needed, associated_streams}; + // Allocations are aligned to alignment_ bytes. new_memory_block's size is exactly bytes_needed, but the part of + // the original memory block which remains unallocated should start at byte divisible by alignment_ + const size_t rounded_up_bytes = roundup_next_multiple(bytes_needed, alignment_); + // ** reduce the size of the block the memory is going to be taken from - if (block_to_get_memory_from_iter->size == bytes_needed) + if (block_to_get_memory_from_iter->size <= rounded_up_bytes) { // this memory block is completely used, remove it free_blocks_.erase(block_to_get_memory_from_iter); @@ -207,8 +207,8 @@ private: else { // there will still be some memory left, update free block size - block_to_get_memory_from_iter->begin += new_memory_block.size; - block_to_get_memory_from_iter->size -= new_memory_block.size; + block_to_get_memory_from_iter->begin += rounded_up_bytes; + block_to_get_memory_from_iter->size -= rounded_up_bytes; } // ** add new used memory block to the list of used blocks @@ -228,10 +228,10 @@ private: return cudaSuccess; } - /// \brief returns the block starting at pointer + /// \brief releases the block starting at pointer /// This function blocks until all work on associated_streams is done /// \param pointer pointer at the begining of the block to be freed - /// \return error status + /// \return cudaSuccess if release was successful, cudaErrorInvalidValue otherwise cudaError_t free_memory_block(void* pointer) { assert(static_cast(pointer) >= buffer_ptr_.get()); @@ -244,9 +244,15 @@ private: [block_start](const MemoryBlock& memory_block) { return memory_block.begin == block_start; }); - assert(block_to_be_freed_iter != std::end(used_blocks_)); + + // * return error if pointer is not valid + if (block_to_be_freed_iter == std::end(used_blocks_)) + { + return cudaErrorInvalidValue; + } // ** wait for all work on associated_streams to finish before freeing up this memory block + assert(!block_to_be_freed_iter->associated_streams.empty()); for (cudaStream_t associated_stream : block_to_be_freed_iter->associated_streams) { // WARNING: The way and place this synchronization is done might change in the future, do not rely on this cudaStreamSynchronize() in the caller. @@ -256,8 +262,15 @@ private: GW_CU_ABORT_ON_ERR(cudaStreamSynchronize(associated_stream)); } + // ** find actual block size + // Allocations are aligned by alignment_ bytes. block_to_be_freed_iter->size is the exact number of requested bytes, but the block + // is actually allocated that-value-rounded-up-to-the-next-number-divisible-by-alignment_ bytes. + // One exception is the block that goes into the last alignment_-divisible block of allocated buffer. In that case actually + // allocated memory goes up to the end of the buffer, even if buffer's size is not divisible by alignment_. In this case number_of_bytes + // is not divisible by alignment_ but the length from the beginning of the block until the end of the buffer + const size_t number_of_bytes = std::min(roundup_next_multiple(block_to_be_freed_iter->size, alignment_), buffer_size_ - block_to_be_freed_iter->begin); + // ** remove memory block from the list of used memory blocks - const size_t number_of_bytes = block_to_be_freed_iter->size; used_blocks_.erase(block_to_be_freed_iter); // ** add the block back the list of free blocks (and merge with any neighbouring free blocks) @@ -346,8 +359,13 @@ private: std::list free_blocks_; /// list of block in use, sorted by memory block beginning location std::list used_blocks_; + + /// number of bytes to align allocations to + static const int32_t alignment_ = 256; // if changing alignment update comments as well }; +} // namespace details + } // namespace genomeworks } // namespace claraparabricks diff --git a/common/base/include/claraparabricks/genomeworks/utils/graph.hpp b/common/base/include/claraparabricks/genomeworks/utils/graph.hpp index 7868659c9..9b58f7117 100644 --- a/common/base/include/claraparabricks/genomeworks/utils/graph.hpp +++ b/common/base/include/claraparabricks/genomeworks/utils/graph.hpp @@ -219,7 +219,7 @@ class Graph std::unordered_map node_labels_; /// An empty list representing no connectivity - const std::vector empty_; + static const std::vector empty_; }; /// \brief DirectedGraph Object representing a directed graph structure @@ -248,6 +248,9 @@ class DirectedGraph : public Graph } } + /// \brief Serialize graph structure to GFA format + /// + /// \return A string encoding the graph in GFA format std::string serialize_to_gfa() const { std::ostringstream gfa_str; diff --git a/common/base/include/claraparabricks/genomeworks/utils/mathutils.hpp b/common/base/include/claraparabricks/genomeworks/utils/mathutils.hpp index 3035d8ec9..c7be754a6 100644 --- a/common/base/include/claraparabricks/genomeworks/utils/mathutils.hpp +++ b/common/base/include/claraparabricks/genomeworks/utils/mathutils.hpp @@ -78,6 +78,37 @@ std::int32_t int_floor_log2(T val) return power; } +/// @brief Rounds up a number to the next number divisible by the given denominator. If the number is already divisible by the denominator it remains the same +/// @param val number to round up +/// @param roundup_denominator has to be positive +/// @tparam Integer has to be integer +template +__host__ __device__ Integer roundup_next_multiple(const Integer val, + int32_t roundup_denominator) +{ + static_assert(std::is_integral::value, "Expected an integer"); + assert(roundup_denominator > 0); + + const Integer remainder = val % roundup_denominator; + + if (remainder == 0) + { + return val; + } + + if (val > 0) + { + // for value 11 and denomintor 4 remainder is 3 so 11 - 3 + 4 = 8 + 4 = 12 + return val - remainder + roundup_denominator; + } + else + { + // remainder is negative is this case, i.e. for value -11 and denominator 4 remainder is -3, + // so -11 - (-3) = -11 + 3 = -8 + return val - remainder; + } +} + } // namespace genomeworks } // namespace claraparabricks diff --git a/common/base/src/graph.cpp b/common/base/src/graph.cpp new file mode 100644 index 000000000..c7779603c --- /dev/null +++ b/common/base/src/graph.cpp @@ -0,0 +1,29 @@ +/* +* Copyright 2019-2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ + +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +const std::vector Graph::empty_ = {}; + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/common/base/tests/CMakeLists.txt b/common/base/tests/CMakeLists.txt index c6c50a8c3..1ed37b7d2 100644 --- a/common/base/tests/CMakeLists.txt +++ b/common/base/tests/CMakeLists.txt @@ -20,6 +20,7 @@ set(TARGET_NAME gwbasetests) set(SOURCES main.cpp + Test_DevicePreallocatedAllocator.cu Test_UtilsCudasort.cu Test_UtilsThreadsafeContainers.cpp TestGraph.cpp diff --git a/common/base/tests/Test_DevicePreallocatedAllocator.cu b/common/base/tests/Test_DevicePreallocatedAllocator.cu new file mode 100644 index 000000000..d73444cb3 --- /dev/null +++ b/common/base/tests/Test_DevicePreallocatedAllocator.cu @@ -0,0 +1,324 @@ +/* +* Copyright 2019-2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ + +#include "gtest/gtest.h" + +#include + +#include +#include +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +TEST(TestDevicePreallocatedAllocator, allocations_do_not_overlap) +{ + CudaStream cuda_stream = make_cuda_stream(); + + std::vector cuda_streams; + cuda_streams.push_back(cuda_stream.get()); + + details::DevicePreallocatedAllocator allocator(2000); + // 0 - 1999: free + + cudaError status; + + void* pointer_from_0_to_999_actually_to_1023 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_0_to_999_actually_to_1023, 1000, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1023: taken + // 1024 - 1999: free + + void* pointer_from_1024_to_1523_actually_to_1535 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1024_to_1523_actually_to_1535, 500, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1535: taken + // 1536 - 1999: free + ASSERT_EQ(static_cast(pointer_from_1024_to_1523_actually_to_1535) - static_cast(pointer_from_0_to_999_actually_to_1023), 1024); + + void* pointer_from_1536_to_1537_actually_to_1791 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1536_to_1537_actually_to_1791, 2, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1791: taken + // 1792 - 1999: free + ASSERT_EQ(static_cast(pointer_from_1536_to_1537_actually_to_1791) - static_cast(pointer_from_1024_to_1523_actually_to_1535), 512); + + void* pointer_from_1792_to_1999_actually_to_1999 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1792_to_1999_actually_to_1999, 208, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1999: taken + ASSERT_EQ(static_cast(pointer_from_1792_to_1999_actually_to_1999) - static_cast(pointer_from_1536_to_1537_actually_to_1791), 256); + + status = allocator.DeviceFree(pointer_from_1792_to_1999_actually_to_1999); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_1536_to_1537_actually_to_1791); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_1024_to_1523_actually_to_1535); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_0_to_999_actually_to_1023); + ASSERT_EQ(status, cudaSuccess); +} + +TEST(TestDevicePreallocatedAllocator, memory_correctly_deallocated) +{ + CudaStream cuda_stream = make_cuda_stream(); + + std::vector cuda_streams; + cuda_streams.push_back(cuda_stream.get()); + + details::DevicePreallocatedAllocator allocator(2000); + // 0 - 1999: free + + cudaError status; + + void* pointer_from_0_to_999_actually_to_1023 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_0_to_999_actually_to_1023, 1000, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1023: taken + // 1024 - 1999: free + + void* pointer_from_1024_to_1523_actually_to_1535 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1024_to_1523_actually_to_1535, 500, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1535: taken + // 1536 - 1999: free + ASSERT_EQ(static_cast(pointer_from_1024_to_1523_actually_to_1535) - static_cast(pointer_from_0_to_999_actually_to_1023), 1024); + + void* pointer_from_1536_to_1537_actually_to_1791 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1536_to_1537_actually_to_1791, 2, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1791: taken + // 1792 - 1999: free + ASSERT_EQ(static_cast(pointer_from_1536_to_1537_actually_to_1791) - static_cast(pointer_from_1024_to_1523_actually_to_1535), 512); + + status = allocator.DeviceFree(pointer_from_1024_to_1523_actually_to_1535); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1023: taken + // 1024 - 1535: free + // 1536 - 1791: taken + // 1792 - 1999: free + + void* pointer_from_1024_to_1027_actually_1279 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1024_to_1027_actually_1279, 4, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1279: taken + // 1280 - 1535: free + // 1535 - 1791: taken + // 1792 - 1999: free + ASSERT_EQ(static_cast(pointer_from_1024_to_1027_actually_1279) - static_cast(pointer_from_0_to_999_actually_to_1023), 1024); + + void* pointer_from_1280_to_1300_actually_1535 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1280_to_1300_actually_1535, 21, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1791: taken + // 1792 - 1999: free + ASSERT_EQ(static_cast(pointer_from_1280_to_1300_actually_1535) - static_cast(pointer_from_1024_to_1027_actually_1279), 256); + + void* pointer_from_1792_to_1800_actually_1999 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1792_to_1800_actually_1999, 9, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1999: taken + ASSERT_EQ(static_cast(pointer_from_1792_to_1800_actually_1999) - static_cast(pointer_from_1536_to_1537_actually_to_1791), 256); + + status = allocator.DeviceFree(pointer_from_1280_to_1300_actually_1535); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_1024_to_1027_actually_1279); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_1536_to_1537_actually_to_1791); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_0_to_999_actually_to_1023); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1999: free + + void* pointer_from_0_to_199_actually_255 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_0_to_199_actually_255, 200, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 255: taken + // 256 - 1999: free + + void* pointer_from_256_to_260_actually_511 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_256_to_260_actually_511, 5, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 511: take + // 512 - 1999: free + ASSERT_EQ(static_cast(pointer_from_256_to_260_actually_511) - static_cast(pointer_from_0_to_199_actually_255), 256); + + void* pointer_from_512_to_515_actually_767 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_512_to_515_actually_767, 4, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 767: take + // 768 - 1999: free + ASSERT_EQ(static_cast(pointer_from_512_to_515_actually_767) - static_cast(pointer_from_256_to_260_actually_511), 256); + + status = allocator.DeviceFree(pointer_from_256_to_260_actually_511); + ASSERT_EQ(status, cudaSuccess); + // 0 - 255: taken + // 256 - 511: free + // 512 - 767: taken + // 768 - 1999: free + + void* pointer_from_768_to_1067_actually_1279 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_768_to_1067_actually_1279, 300, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 255: taken + // 256 - 511: free + // 512 - 1279: taken + // 1280 - 1999: free + ASSERT_EQ(static_cast(pointer_from_768_to_1067_actually_1279) - static_cast(pointer_from_512_to_515_actually_767), 256); + + void* pointer_from_256_to_270_actually_511 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_256_to_270_actually_511, 15, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1279: taken + // 1280 - 1999: free + ASSERT_EQ(static_cast(pointer_from_256_to_270_actually_511) - static_cast(pointer_from_0_to_199_actually_255), 256); + + void* pointer_from_1280_to_1290_actually_1535 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1280_to_1290_actually_1535, 11, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + // 0 - 1535: taken + // 1536 - 1999: free + ASSERT_EQ(static_cast(pointer_from_1280_to_1290_actually_1535) - static_cast(pointer_from_768_to_1067_actually_1279), 512); + + status = allocator.DeviceFree(pointer_from_1280_to_1290_actually_1535); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_768_to_1067_actually_1279); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_512_to_515_actually_767); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_256_to_270_actually_511); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_0_to_199_actually_255); + ASSERT_EQ(status, cudaSuccess); +} + +TEST(TestDevicePreallocatedAllocator, not_enough_memory_left) +{ + CudaStream cuda_stream = make_cuda_stream(); + + std::vector cuda_streams; + cuda_streams.push_back(cuda_stream.get()); + + details::DevicePreallocatedAllocator allocator(2000); + // 0 - 1999: free + + cudaError status; + + void* pointer_from_0_to_1499_actually_1535 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_0_to_1499_actually_1535, 1500, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + ASSERT_NE(pointer_from_0_to_1499_actually_1535, nullptr); + // 0 - 1535: taken + // 1536 - 1999: free + + void* pointer_from_1536_to_2000_actually_error = pointer_from_0_to_1499_actually_1535; // initially set to some value to make sure allocator.DeviceAllocate() sets it to nullptr if allocation was not successful + status = allocator.DeviceAllocate(&pointer_from_1536_to_2000_actually_error, 465, cuda_streams); + ASSERT_EQ(status, cudaErrorMemoryAllocation); + ASSERT_EQ(pointer_from_1536_to_2000_actually_error, nullptr); + // 0 - 1535: taken + // 1536 - 1999: free + + void* pointer_from_1536_to_1999_actually_1999 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1536_to_1999_actually_1999, 464, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + ASSERT_NE(pointer_from_1536_to_1999_actually_1999, nullptr); + // 0 - 1999: taken + + status = allocator.DeviceFree(pointer_from_1536_to_1999_actually_1999); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_0_to_1499_actually_1535); + ASSERT_EQ(status, cudaSuccess); +} + +TEST(TestDevicePreallocatedAllocator, no_memory_left) +{ + CudaStream cuda_stream = make_cuda_stream(); + + std::vector cuda_streams; + cuda_streams.push_back(cuda_stream.get()); + + details::DevicePreallocatedAllocator allocator(2000); + // 0 - 1999: free + + cudaError status; + + void* pointer_from_0_to_1499_actually_1535 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_0_to_1499_actually_1535, 1500, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + ASSERT_NE(pointer_from_0_to_1499_actually_1535, nullptr); + // 0 - 1535: taken + // 1536 - 1999: free + + void* pointer_from_1536_to_1999_actually_1999 = nullptr; + status = allocator.DeviceAllocate(&pointer_from_1536_to_1999_actually_1999, 464, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + ASSERT_NE(pointer_from_1536_to_1999_actually_1999, nullptr); + // 0 - 1999: taken + + void* pointer_to_unsuccessful_allocation = pointer_from_1536_to_1999_actually_1999; // set it to some value to make sure it gets reset to nullptr + status = allocator.DeviceAllocate(&pointer_to_unsuccessful_allocation, 1, cuda_streams); + ASSERT_EQ(status, cudaErrorMemoryAllocation); + ASSERT_EQ(pointer_to_unsuccessful_allocation, nullptr); + + status = allocator.DeviceFree(pointer_from_1536_to_1999_actually_1999); + ASSERT_EQ(status, cudaSuccess); + status = allocator.DeviceFree(pointer_from_0_to_1499_actually_1535); + ASSERT_EQ(status, cudaSuccess); +} + +TEST(TestDevicePreallocatedAllocator, deallocating_invalid_pointer) +{ + CudaStream cuda_stream = make_cuda_stream(); + + std::vector cuda_streams; + cuda_streams.push_back(cuda_stream.get()); + + details::DevicePreallocatedAllocator allocator(2000); + + cudaError status; + + void* valid_ptr = nullptr; + status = allocator.DeviceAllocate(&valid_ptr, 1500, cuda_streams); + ASSERT_EQ(status, cudaSuccess); + ASSERT_NE(valid_ptr, nullptr); + + void* invalid_ptr = static_cast(static_cast(valid_ptr) + 10); + status = allocator.DeviceFree(invalid_ptr); + ASSERT_EQ(status, cudaErrorInvalidValue); + + void* null_ptr = nullptr; + status = allocator.DeviceFree(null_ptr); + ASSERT_EQ(status, cudaSuccess); + + // deallocating nullptr does nothing, but is a success + status = allocator.DeviceFree(nullptr); + ASSERT_EQ(status, cudaSuccess); + + status = allocator.DeviceFree(valid_ptr); + ASSERT_EQ(status, cudaSuccess); + + // deallocating previously deallocated pointer results in error + status = allocator.DeviceFree(valid_ptr); // pointer not valid anymore + ASSERT_EQ(status, cudaErrorInvalidValue); +} + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaaligner/CMakeLists.txt b/cudaaligner/CMakeLists.txt index 6500a0fad..59b5e9350 100644 --- a/cudaaligner/CMakeLists.txt +++ b/cudaaligner/CMakeLists.txt @@ -20,9 +20,9 @@ set(MODULE_NAME cudaaligner) # Project specific NVCC flags if((CUDA_VERSION_MAJOR GREATER 10) OR (CUDA_VERSION_MAJOR EQUAL 10 AND CUDA_VERSION_MINOR GREATER 0)) -set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} -std=c++14 --expt-relaxed-constexpr") +set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} -std=c++14 -arch=compute_60 --expt-relaxed-constexpr") else() -set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} -std=c++14") +set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} -std=c++14 -arch=compute_60") endif() message(STATUS "nvcc flags for ${MODULE_NAME}: ${CUDA_NVCC_FLAGS}") @@ -53,7 +53,7 @@ target_link_libraries(${MODULE_NAME} gwbase cub) target_compile_options(${MODULE_NAME} PRIVATE -Werror -Wall -Wextra) if (gw_optimize_for_native_cpu) - target_compile_options(cudapoa PRIVATE -march=native) + target_compile_options(${MODULE_NAME} PRIVATE -march=native) endif() target_include_directories(${MODULE_NAME} @@ -65,6 +65,7 @@ target_include_directories(${MODULE_NAME} target_compile_options(${MODULE_NAME} PRIVATE -Werror) add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/include) +add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/README.md) # Add tests folder add_subdirectory(tests) diff --git a/cudaaligner/README.md b/cudaaligner/README.md new file mode 100644 index 000000000..270eb02fb --- /dev/null +++ b/cudaaligner/README.md @@ -0,0 +1,15 @@ +# cudaaligner + +The `cudaaligner` package provides GPU-accelerated global alignment. + +## Library +Built as `libcudaaligner.[so|a]`. + +* Short and long read support +* Banded implementation with configurable band width for flexible performance and accuracy trade-off + +APIs documented in [include](include/claraparabricks/genomeworks/cudaaligner) folder. + +## Sample +[sample_cudaaligner](samples/sample_cudaaligner.cpp) - A prototypical binary to showcase the use of `libcudaaligner` APIs. + diff --git a/cudaaligner/samples/sample_cudaaligner.cpp b/cudaaligner/samples/sample_cudaaligner.cpp index db147faab..fb147876e 100644 --- a/cudaaligner/samples/sample_cudaaligner.cpp +++ b/cudaaligner/samples/sample_cudaaligner.cpp @@ -26,6 +26,7 @@ #include #include #include +#include using namespace claraparabricks::genomeworks; using namespace claraparabricks::genomeworks::genomeutils; diff --git a/cudaaligner/src/myers_gpu.cu b/cudaaligner/src/myers_gpu.cu index e03d332fd..c18a3f2b6 100644 --- a/cudaaligner/src/myers_gpu.cu +++ b/cudaaligner/src/myers_gpu.cu @@ -425,19 +425,25 @@ __device__ int32_t myers_backtrace_banded(int8_t* path, device_matrix_view= 0); + assert(diagonal_end >= diagonal_begin); + assert(diagonal_end >= 2); // this should only break if target_size == 0 - which is not valid input. + int32_t i = band_width; int32_t j = target_size; const WordType last_entry_mask = band_width % word_size != 0 ? (WordType(1) << (band_width % word_size)) - 1 : ~WordType(0); - nw_score_t myscore = score((i - 1) / word_size, j); // row 0 is implicit, NW matrix is shifted by i -> i-1 (see get_myers_score) - int32_t pos = 0; + const nw_score_t last_diagonal_score = diagonal_end < 2 ? out_of_band : get_myers_score(1, diagonal_end - 2, pv, mv, score, last_entry_mask) + 2; + nw_score_t myscore = score((i - 1) / word_size, j); // row 0 is implicit, NW matrix is shifted by i -> i-1, i.e. i \in [1,band_width] for get_myers_score. (see get_myers_score) + int32_t pos = 0; while (j >= diagonal_end) { - int8_t r = 0; - nw_score_t const above = i <= 1 ? j : get_myers_score(i - 1, j, pv, mv, score, last_entry_mask); - nw_score_t const diag = i <= 1 ? j - 1 : get_myers_score(i - 1, j - 1, pv, mv, score, last_entry_mask); - nw_score_t const left = get_myers_score(i, j - 1, pv, mv, score, last_entry_mask); + int8_t r = 0; + // Worst case for the implicit top row (i == 0) of the bottom right block of the NW is the last diagonal entry on the same row + (j - diagonal_end) * indel cost. + nw_score_t const above = i <= 1 ? (last_diagonal_score + j - diagonal_end) : get_myers_score(i - 1, j, pv, mv, score, last_entry_mask); + nw_score_t const diag = i <= 1 ? (last_diagonal_score + j - 1 - diagonal_end) : get_myers_score(i - 1, j - 1, pv, mv, score, last_entry_mask); + nw_score_t const left = i < 1 ? (last_diagonal_score + j - 1 - diagonal_end) : get_myers_score(i, j - 1, pv, mv, score, last_entry_mask); if (left + 1 == myscore) { r = static_cast(AlignmentState::insertion); @@ -452,6 +458,7 @@ __device__ int32_t myers_backtrace_banded(int8_t* path, device_matrix_view(AlignmentState::match) : static_cast(AlignmentState::mismatch)); myscore = diag; --i; @@ -463,9 +470,10 @@ __device__ int32_t myers_backtrace_banded(int8_t* path, device_matrix_view= diagonal_begin) { int8_t r = 0; - nw_score_t const above = i <= 1 ? j : get_myers_score(i - 1, j, pv, mv, score, last_entry_mask); + nw_score_t const above = i <= 1 ? out_of_band : get_myers_score(i - 1, j, pv, mv, score, last_entry_mask); nw_score_t const diag = i <= 0 ? j - 1 : get_myers_score(i, j - 1, pv, mv, score, last_entry_mask); nw_score_t const left = i >= band_width ? out_of_band : get_myers_score(i + 1, j - 1, pv, mv, score, last_entry_mask); + // out-of-band cases: diag always preferrable, since worst-case-(above|left) - myscore >= diag - myscore always holds. if (left + 1 == myscore) { r = static_cast(AlignmentState::insertion); @@ -481,6 +489,7 @@ __device__ int32_t myers_backtrace_banded(int8_t* path, device_matrix_view(AlignmentState::match) : static_cast(AlignmentState::mismatch)); myscore = diag; --j; @@ -494,6 +503,7 @@ __device__ int32_t myers_backtrace_banded(int8_t* path, device_matrix_view band_width ? out_of_band : get_myers_score(i, j - 1, pv, mv, score, last_entry_mask); + // out-of-band cases: diag always preferrable, since worst-case-(above|left) - myscore >= diag - myscore always holds. if (left + 1 == myscore) { r = static_cast(AlignmentState::insertion); @@ -508,6 +518,7 @@ __device__ int32_t myers_backtrace_banded(int8_t* path, device_matrix_view(AlignmentState::match) : static_cast(AlignmentState::mismatch)); myscore = diag; --i; diff --git a/cudaaligner/tests/Test_ApproximateBandedMyers.cpp b/cudaaligner/tests/Test_ApproximateBandedMyers.cpp index daa585697..2492d24b9 100644 --- a/cudaaligner/tests/Test_ApproximateBandedMyers.cpp +++ b/cudaaligner/tests/Test_ApproximateBandedMyers.cpp @@ -56,8 +56,80 @@ class TestApproximateBandedMyers : public ::testing::TestWithParam { }; +void implicit_new_entries_test_impl(const std::string& query, const std::string& target, const std::string& expected_cigar) +{ + using namespace claraparabricks::genomeworks::cudaaligner; + using namespace claraparabricks::genomeworks; + const int32_t max_bw = 7; + DefaultDeviceAllocator allocator = create_default_device_allocator(); + std::unique_ptr aligner = std::make_unique(-1, + max_bw, + allocator, + nullptr, + 0); + ASSERT_EQ(StatusType::success, aligner->add_alignment(query.c_str(), query.length(), target.c_str(), target.length())) + << "Could not add alignment to aligner"; + aligner->align_all(); + aligner->sync_alignments(); + const std::vector>& alignments = aligner->get_alignments(); + ASSERT_EQ(get_size(alignments), 1); + ASSERT_EQ(alignments[0]->get_status(), StatusType::success); + ASSERT_EQ(alignments[0]->is_optimal(), false); + ASSERT_EQ(alignments[0]->convert_to_cigar(), expected_cigar); +} + } // namespace +TEST(TestApproximateBandedMyersStatic, ImplicitNWEntries1) +{ + // The banded Myers implementation uses implicit entries for the 0-th row of the NW matrix (and the band), + // which is assumed to be the worst case value. This does not pose a problem on the top left block and + // the diagonal band, but on the lower right block there are cases where the backtrace runs through this worst case + // - which is technically still part of the band. This tests this specific corner case. + + // * = tested implicit 0-row entry + // Band of the NW matrix: + // top left block of NW m.| diagonal band (each column shifted by one row) | bottom right block + // NW_(i,j), index i of first shown row: + // 1 1 1 1 1 1 1 | 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 | 20 20 20 20 20 20 + // + // A A C C G G | T T A A A A C C C C G G G G G T T A A | A C G G T T + // row 0 (implicit): | * | * + // A 1 0 1 2 3 4 5 |A 5 C 5 C 5 G 5 G 5 T 5 T 5 A 5 A 5 C 5 C 5 G 5 G 5 T 6 T 7 A 8 A 9 C 10 C 11 |C 12 12 13 14 15 16 + // A 2 1 0 1 2 3 4 |C 4 C 4 G 4 G 4 T 4 T 4 A 4 A 4 C 4 C 4 G 4 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 |G 12 13 12 13 14 15 + // C 3 2 1 0 1 2 3 |C 3 G 3 G 3 T 3 T 3 A 3 A 3 C 3 C 3 G 4 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 G 12 |G 12 13 13 12 13 14 + // C 4 3 2 1 0 1 2 |G 2 G 2 T 2 T 2 A 2 A 2 C 2 C 2 G 3 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 G 12 T 13 |T 13 13 14 13 12 13 + // G 5 4 3 2 1 0 1 |G 1 T 1 T 1 A 1 A 1 C 2 C 2 G 3 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 G 12 T 12 T 12 |T 13 14 14 14 13 12 + // G 6 5 4 3 2 1 0 |T 0 T 0 A 0 A 0 C 1 C 2 G 3 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 10 G 11 T 11 T 11 T 12 |T 13 14 15 15 14 13 + // T 7 6 5 4 3 2 1 |T 1 A 1 A 1 C 1 C 2 G 3 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 10 G 10 T 10 T 10 T 11 T 12 |T 13 14 15 16 15 14 + + implicit_new_entries_test_impl("AACCGGTTAACCGGTTAACCGGTTTT", + "AACCGGTTAAAACCCCGGGGGTTAAACGGTT", + "10M2I2M2I7M3I5M2D"); +} + +TEST(TestApproximateBandedMyersStatic, ImplicitNWEntries2) +{ + // * = tested implicit 0-row entry + // Band of the NW matrix: + // top left block of NW mat, | diagonal band (each column shifted by one row) | bottom right block + // NW_(i,j), index i of first shown row: + // 1 1 1 1 1 1 1 1 | 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 | 19 19 19 19 19 19 + // + // A A C C G G T | T A A A A C C C C G G G G G T T A A | C C G G T T + // row 0 (implicit): | * | + // A 1 0 1 2 3 4 5 6 |A 6 C 6 C 6 G 6 G 6 T 6 T 6 A 6 A 6 C 6 C 6 G 6 G 6 T 7 T 7 A 8 A 8 C 9 |C 9 10 11 12 13 14 + // A 2 1 0 1 2 3 4 5 |C 5 C 5 G 5 G 5 T 5 T 5 A 5 A 5 C 5 C 5 G 5 G 5 T 6 T 7 A 8 A 9 C 9 C 10 |C 9 9 10 11 12 13 + // C 3 2 1 0 1 2 3 4 |C 4 G 4 G 4 T 4 T 4 A 4 A 4 C 4 C 4 G 4 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 |G 10 10 9 10 11 12 + // C 4 3 2 1 0 1 2 3 |G 3 G 3 T 3 T 3 A 3 A 3 C 3 C 3 G 4 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 G 12 |G 11 11 10 9 10 11 + // G 5 4 3 2 1 0 1 2 |G 2 T 2 T 2 A 2 A 2 C 2 C 2 G 3 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 G 12 T 13 |T 12 12 11 10 9 10 + // G 6 5 4 3 2 1 0 1 |T 1 T 1 A 1 A 1 C 2 C 2 G 3 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 11 G 12 T 12 T 13 |T 13 13 12 11 10 9 + // T 7 6 5 4 3 2 1 0 |T 0 A 0 A 0 C 1 C 2 G 3 G 4 T 5 T 6 A 7 A 8 C 9 C 10 G 10 G 11 T 11 T 12 T 13 |T 14 14 13 12 11 10 + implicit_new_entries_test_impl("AACCGGTTAACCGGTTAACCGGTTT", + "AACCGGTTAAAACCCCGGGGGTTAACCGGTT", + "10M2I2M2I3M2I3M1I6M1D"); +} + TEST_P(TestApproximateBandedMyers, EditDistanceMonotonicallyDecreasesWithBandWidth) { using namespace claraparabricks::genomeworks::cudaaligner; diff --git a/cudaextender/CMakeLists.txt b/cudaextender/CMakeLists.txt new file mode 100644 index 000000000..8c00a1147 --- /dev/null +++ b/cudaextender/CMakeLists.txt @@ -0,0 +1,78 @@ +# +# Copyright 2020 NVIDIA CORPORATION. +# +# Licensed under the Apache License, Version 2.0 (the "License"); +# you may not use this file except in compliance with the License. +# You may obtain a copy of the License at +# +# http://www.apache.org/licenses/LICENSE-2.0 +# +# Unless required by applicable law or agreed to in writing, software +# distributed under the License is distributed on an "AS IS" BASIS, +# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +# See the License for the specific language governing permissions and +# limitations under the License. +# +set(MODULE_NAME cudaextender) + +# Process data subdirectory first +add_subdirectory(data) + +GitVersion() + +configure_file(${PROJECT_SOURCE_DIR}/common/base/src/version.cpp.in + ${CMAKE_CURRENT_BINARY_DIR}/version.cpp) + +# Project specific NVCC flags, --expt-relaxed-constexpr is being added to allow using numeric_limits inside device kernels. +# Using in CUDA 10.1+ to avoid compilation issues with CUDA <= 10.0. +set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} -std=c++14") +if (gw_cuda_after_10_0) + set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} --expt-relaxed-constexpr") +endif () +if (gw_cuda_gen_all_arch) + CUDA_SELECT_NVCC_ARCH_FLAGS(ARCH_FLAGS "Common") +else () + CUDA_SELECT_NVCC_ARCH_FLAGS(ARCH_FLAGS "Auto") +endif () +set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} ${ARCH_FLAGS}") +message(STATUS "nvcc flags for ${PROJECT_NAME}: ${CUDA_NVCC_FLAGS}") + +get_property(gw_library_type GLOBAL PROPERTY gw_library_type) +cuda_add_library(${MODULE_NAME} ${gw_library_type} + src/cudaextender.cpp + src/extender.cpp + src/ungapped_xdrop.cu + src/ungapped_xdrop_kernels.cu + ${CMAKE_CURRENT_BINARY_DIR}/version.cpp) + +target_link_libraries(${MODULE_NAME} gwbase gwio cub) + +target_compile_options(${MODULE_NAME} PRIVATE -Werror -Wall -Wextra) +if (gw_optimize_for_native_cpu) + target_compile_options(${MODULE_NAME} PRIVATE -march=native) +endif () + +target_include_directories(${MODULE_NAME} + PUBLIC + $ + $ + ) + +add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/include) +add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/README.md) + +install(TARGETS ${MODULE_NAME} + COMPONENT gwlogging + EXPORT ${MODULE_NAME} + DESTINATION lib + INCLUDES DESTINATION include + ) +install(DIRECTORY include/ DESTINATION include) +install(EXPORT ${MODULE_NAME} DESTINATION cmake) + +# Add other folders. +add_subdirectory(samples) +add_subdirectory(tests) + +# Add auto formatting. +gw_enable_auto_formatting("${CMAKE_CURRENT_SOURCE_DIR}") diff --git a/cudaextender/README.md b/cudaextender/README.md new file mode 100644 index 000000000..6d03d61d2 --- /dev/null +++ b/cudaextender/README.md @@ -0,0 +1,26 @@ +# cudaextender + +This package implements CUDA-accelerated seed-extension algorithms that use seed positions in +encoded input strands to extend and compute the alignment between the strands. +Currently this module implements the ungapped X-drop algorithm, adapted from +[SegAlign's](https://github.com/gsneha26/SegAlign) Ungapped Extender authored by +Sneha Goenka (gsneha@stanford.edu) and Yatish Turakhia (yturakhi@uscs.edu). + +## Library +Built as `libcudaextender.[so|a]` + +* Ungapped X-Drop extension + +`cudaextender` provides host and device pointer APIs to enable ease of integration with other +producer/consumer modules. The user is expected to handle all memory transactions and device +sychronizations for the device pointer API. The host pointer API abstracts those operations away. +Both APIs are documented here: [extender.hpp](include/claraparabricks/genomeworks/cudaextender/extender.hpp) + +### Encoded Input +`cudaextender` expects the input strands to be encoded as integer sequences. +This encoding scheme is documented here: [utils.hpp](include/claraparabricks/genomeworks/cudaextender/utils.hpp) +file. The provided `encode_sequence()` helper function will encode the input strands on CPU with +the expected scheme. + +## Sample +[sample_cudaextender](samples/sample_cudaextender.cpp) - Protoype to show the usage of host and device pointer APIs on FASTA sequences. diff --git a/cudaextender/data/CMakeLists.txt b/cudaextender/data/CMakeLists.txt new file mode 100644 index 000000000..11ce93724 --- /dev/null +++ b/cudaextender/data/CMakeLists.txt @@ -0,0 +1,19 @@ +# +# Copyright 2020 NVIDIA CORPORATION. +# +# Licensed under the Apache License, Version 2.0 (the "License"); +# you may not use this file except in compliance with the License. +# You may obtain a copy of the License at +# +# http://www.apache.org/licenses/LICENSE-2.0 +# +# Unless required by applicable law or agreed to in writing, software +# distributed under the License is distributed on an "AS IS" BASIS, +# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +# See the License for the specific language governing permissions and +# limitations under the License. +# +set(CUDAEXTENDER_DATA_DIR "${CMAKE_CURRENT_SOURCE_DIR}/../data") +configure_file(cudaextender_file_location.hpp.in ${PROJECT_BINARY_DIR}/data/cudaextender_file_location.hpp @ONLY) + +set_property(GLOBAL PROPERTY cudaextender_data_include_dir "${PROJECT_BINARY_DIR}/data") diff --git a/cudaextender/data/cudaextender_file_location.hpp.in b/cudaextender/data/cudaextender_file_location.hpp.in new file mode 100644 index 000000000..56487d77a --- /dev/null +++ b/cudaextender/data/cudaextender_file_location.hpp.in @@ -0,0 +1,18 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +#pragma once + +#cmakedefine CUDAEXTENDER_DATA_DIR "@CUDAEXTENDER_DATA_DIR@" diff --git a/cudaextender/data/sample.fa b/cudaextender/data/sample.fa new file mode 100644 index 000000000..b44bb7128 --- /dev/null +++ b/cudaextender/data/sample.fa @@ -0,0 +1,5001 @@ +>chr1 +CACAGACTTTTCTGGATATGAACATACAGTAGAAAAAGAATTGAACAACT +ATCCCATCACCCTAGCTGAATGTAGAGAAATGATTAATAGTAAGAAATGT +GGATACGGAACTTTATCAAAAGGTAGTTCTAACGTATGGAGTACAAATAA +TAAAATCGAAGTTGATTACCCAAATAGATTTACAAGCTTCTTCTCACCTA +AAAGATTCCACAAAGAAAATTGTATAGTTATTGAGACGAAAGTTTATTCC +CATTTTAATCAATCTAAGCCAACCAATATTTTAGCTGATATGAACAATTG +CAAGTATCAAGACGGTTTCTGCGagatcaagaaaaatgaaattataacAT +GGGATGTCAACAGAGATCAGAAATGTCAATTTATCTCTATTGGAATACTT +GATGGGATGTACAATAACAAACTCTGGGTTAACAATAAGAACCAAATTGc +gttaaattttgaaacacagAAGATTGTGAATGATTGTAACATAGACCTAA +TGATTAGTGATGAGGGTTTTGCTGTaaaaagaattgaaagatCTCAATAT +TCTCCAAGACACATTCCTATTCCAATCCCATCATATTCTCAACAAGATAT +TCAACGTCAAAGACAACAACAGGAGGACGACAGAAGAAAACGTGAACAAG +AGGAACAACAGAGAAAGCGGGAGCAAGAAGATAGTAGGAGACGGGATCaa +gaagatatcagaaaacgGGATCAAGAAGATGCTAGAAGACGTGATCaaga +aagacaaaaacagaatgaagctgattttgaaaagaggaaacaagaaaagc +tgaagaaggaagaagaacttgagaaaaagaaacaggagaaaactaagaaa +gctcaggaagaggctgaaagaaaagaaatcgaagCATTGAGGAAGCTACG +GAAAGATGAAGACTGGACAGTTCATGATGAGAAATCGAAAGGTGTAGACA +AAAAATCCAACAGAACTAAAAGAGAAATCTTTCAACCATTACCATTACca +aattatgatgaatatttaAAGATCAAACAAGACTGTGATAACTTACCTAG +TTATGAAGCATTCAAGAATAGTAGAGAAGGATGTGATTCACTTACAACTT +ATACAGATTTTATAAACannnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnGTCTTATAAGAGAA +AATCCAAGAAGATACAtccaaaaacaattgaatcaTTCAGCCATCAAAGT +GAGATTCATAGATTCTCAGGATCCAATAGTACAAGTTACATTTTGTAAAG +AAATTGATGAAGAAGAGATTGACTTTATAGACGTTACTCATTTTGATGGA +TACAAGTTAAGTATTGCTCTCACACTCGGACAAATACCAATCAAGATAAA +AAGTCTAGGAGATAAAATTTGGTATTACAAGAATGATAATTTTGGAGGAG +TGATATCAAGTAAACCTCAGCTTCATCCTATGATCGATTATAGAACTAAC +ATTACTAatatgaaaagtttcaaagagtTTGATTTAAAATTCTTAGATGA +CAAAGTAGTATTCCATGAGCACATTCTATTAGATTTGAAGACAAATATTG +AAGAAGAACTCATTgaagaaatgagagaaaagtCTGATGTTTCAATTGAA +GCTCATGCTAGTAATCAAGATTCTACTTTACCTCATGAAATATTAGACGA +TGTAGAAGGATTCTTTGGAAAGTGGTGGCTTAGAATTTGGAGAGTTGGTG +TTACTTTGCCAGCAATGTTCGTATACCTATTTATAGCTAGATCATTTTGG +ATGATACtttctccaaaaacttttattgatagaaaaaatagaaaaaggaa +aagggagTATGAGGCTGTAGAACTAAGAGAAATGCCGTCTATTCAATCTC +TTACTGTTGATTAATTTTTAACTAAATAAATGAGATTCTTTAATGCTGGA +AATGCTTCTAGTTATTTAATTATGGGTTCAGAAGAAAAACCTAAAGTAGA +ACTTGTAGAAAATTGTAGAAAGCCTGATATGAACCTATAGATAGTCTTAA +TAAGTCAATTAGAGAGTTGGTATTTGATGGTATGAAAGAAATAGAACTTC +CTGATGTTGAAGATGTAGTTGGGGTCTTAGCTACAAAATATTTAGACTTT +ATGAACGCCCATTTATCACTGGAATCTGCATTATATCTTTTGGATTCTTT +ATCAAAACCTTGGTACAGAGCATTGGAgcataataatattttttggtaat +ttgaaGAATCTTCAGTTGTAACCTTGTTTAGATCAGGAGACTTTTTGAGT +AGTAATTCCATCAGACCCTCAGTTGCTGTGTATTCTTCATTATTAACTTT +GATAATATTCTGATCGAATGTAATGTCTTTGTTACCAATAGCATACTTCT +TTTCTGCTTTGTTGAACTTGATTGAGTATCCAGCATTACTTCTATCTGAA +TTATCTTGAAGATAACTTACAATTAGATTACTTACAACTTGAGGTGGAGA +AGAACTAGGTAGAGAGGGAGGTAGGATTACTGAGGGTTGCTTAATGAGAC +TTTTACGATTTGTCTTTGGTGTCGnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnGAAGGAGATTTAAAGTTGTTGAGAGTTTCTACTATTTTATTCTT +TTCATCAATTATTTCTTCTTGTAGTTTTTTGTGGATTCTAAAATAGGTTT +AAATACTTCAATTCTATAATCTTCTACATGTTCTAAATCTGATCGCTCTT +GtaaattcttgattttatgctctttccgatttttcaaaaagtcttgAACA +ATGAAATTTCGCTTTTTAGGGTCATATATCTCAACTACAGAATGCATTTA +TTACAGGAAATATCATCGATTTTAGGTTGATTtattcaatatttctgaaa +atttattatagGTTTTAAATGATACTTTTCGTGCTTTATAAATGGAACAA +GttgattacaaaaaattggataggGATCAACTACGAAAACTTGTAAGAAA +CAGAACTAACACAAGTAGAGATGATGTTAGAAATATGAGCGTGCCTGAAA +TGCGTAAAATACTCAAACAGCTGGATATAGATGAACTTAGCGAAAAGTCA +AATCTTCAAATGATGAATCTATTTCCCTTCGATGAAACTGTCTTTAGTGA +TTACAAAGAAGTTGGTGATACGTTGAGAGATACTTTTCACagtggaaatt +ctaaaacattAGAATCCTTTTTAGATAAGAAAGGGCCTgatattgtgaaa +aaaatttatgaaaatagtGTGAAAATATATGTATCCTTAGAATGTGAAAT +GATAAAAGAAGGTACAGAAGATACCCAAGTAGCTCATTTGACTACAAAAA +GTGTATTATTGAATCCAGGTGATAGTAGAATTGActtcatgaaaaatatt +aaatctGATTTAGTAAATAGATTAGAACATTATCAAAGCAGAGGATCAGG +ATTTAGATTGAATAGAATTATTGGCTTGAGAATGTCTCAAACTAAGATTA +TGCCATTATCAGGATCAAAATATATTGAATTACCAGATtggataaaaaat +aaaaaagcagTAGTCAATGTTCAAAAcaaagatgaaaaatgttttatgtg +GTGTATTCTAGCACACTTATATCCAGTTGAAGAACATCCTGAACGAATAA +GCAAATATAAAGAGCATGCTTCTAAAATTAATTTCGAAGGTTTCGAATTT +CCTTTCCAAGTTAAAGATGTAGATAAGTTTGAGAAGAGAAATAACTTGGC +TGTTAATATTGTAACTCATGATGTCTCAGGACCAGCAATAATTGAGTCAT +ATAAAGTATCTAAAAACATCAACGTAGATTTAAGTAGAGTGATAAACCTT +TTGTTAGTAACTGATGAATCTGGAGAAGGTCATTACTGTTtgattaaaaa +tattgatagaTTGATGAACACCCAAAATAGTAGAAGCAATAAATTTTGTA +TTAGATGTCATAATAACTTTTACAATGcagagaagtttgaaaatcattta +ggTGACTGTATGAGTAATGCTCCAATGCAAATGATTAAACCTTCCAATGA +TtatattgaattttctaatattcaGAAAACACAGAAACATAGATTTGTAT +GTTACGCCGATTTTGAATCTGTTATCTATAAAATTGATTCTGTTAACAAT +TCTCCTAACAAATCTTGGAGTGAGAATGTTGGTAACATAAGGCCTCTGCT +TCTGTGTGATGTTGGTTGATTCTTTCACTCAGAGCATTTACGAAATGAAG +AGCTATGTTGGATATAATACTATTTTAAAAGTCAATGAGTATATCTTAGA +TGTATGTGCAAGACTATTGAATAAAGgtgatgagaaaatgaaaaatttaa +ccAATGAAGAGTTAGAATGTTATAATAACTGTAATTCATGTCCTCAGTGT +GAGAATGTGTTTGATGGGGATAAAGTTAGAGATCACGATCATTGGACTGG +ATTATACAGAGGGCCTCTATGTAATGCATGTAACCTATTGAAATGTAGAA +ATAATTTTATACCAGTATTTTTCCATAATCTTAAAGGCTATGACTCACAT +CATATAATTTGTGATGAGGAATCAAGCAAactattgaagaaaaaaggtgT +TGAAATTAAAAGCATCTCAGCAAATATAGAAAAGTTTATTAGTTTCAGTT +ATATATACAAAAATCCTAAACGATGTGAAATAAGATTTTTAGATAGTTTT +GGTTTTATGCCTTCCAGTCTGGACTATCTCAGCAGTAACCTACAAGATGA +AGAATGTGTGATTACTAATAAGTATCACAAGAATGAAAAGATGTTTAATC +TATTAAGACGCAAAGGTGTGATCCATATATTTTATGGATTCCTTCAAAAA +GTATTCTAACGAAGAACTTCCTCCAATTGAAAACTTCTACAATGCTCTAT +CTGGTGAAAATATTAGTGAAGAGAGTTATAAATATGCTCAGAAAGTATGG +AAGGAAACAAATTGTAAAACTTTAGAAGACTACACTAGAATTTATATGAT +TAATGATGTGCTACTATTAGctgatgtttttgaaactttcagaaatgtgt +ctcTCAAAGAATATAAGTTAGATCCATGTTGGTACTATACATCTCCCGGA +TTAGCTTGGGATGCTATGTTAAAGAAAACTGGAGTTAAGCTACAGACAAT +CAAGGATATTGAAATGtataattttattgaaaaaggtATTCGAGGAGGTA +TGTGTAATACCATGCTAAGATATTCGAAAGCTAATAACAAGTACATGTCT +AATTATAATCCCGAAGAGGAATCAAAATACTTATTATATCTAGATGCAAA +TAACTTATATGGATGGGCAATGAGTCAGAAATTACCATATGATGAATTCG +AATTCGTTGAAGACTTTACCTTAGAAATGATAGATGATCttgtttcaaaa +gaaaaaggttGCATACTAGAAGTAGATTTAGATTATCCAGAAGAATTACA +TGATAAACATAATGATTTACCTTTCTGTCCAGAGAATAAACGAGTTGGAT +CTACCAATAAACTAATAAATGATTTTAGTCCAAAGAGAAATTATGTAATA +CATTATAAAGCCCTTTTGCAAGTTTTAGATCATGgattaattttgaagaa +aattcatAGAGTTATTACTTTTAAAGAAAGCAATTGGTTATCTTCTTACA +TAGAACTGAATACtaacttgagaaaaaatgccaagaatgattttgagaaa +gacTTTTTCAAGCTCATGAACAATTCTGTCTTTGGTAAAACTATGGAGAA +CGTTAGAAATAGAGTGGATGTCAAAGTGGTGTCAAATATGGATAAAGTTA +TGAAACTAGCTGCTAGCAATAATTTTAAACAGAGACATATTATAAATGAG +AATATGATTTTGTAGAGATGACTCAGAAGAATATTAAATTAGATAAGCCA +ATTTATGTGGGGATGTCTATTTTAGATTTGAGCAAGTATCTAATGTATGA +GTTCCACTATGATGTGATGCTTCCAAAATATTCTTCGAATTTGAGACTGT +GCTATCAAGATACTGATTCTTATATTTATGAAATTAAAACAGACGATGTT +TATGAAGATATGTTAGCTATGAAAGaacactttgatttttcggattatCC +AAAAGAAAATAAACTTCATAGCattgagaacaaaaaagttattggtAAAT +TTAAAGATGAGTTGAATGGTAAAATAATGACTGAGATTGTAGCCTTTAGA +CCAAAACAATATGCTTTTAAAACTGATGAGGGAATGGAGTCTAAAAGAAA +TAAAGGTGTGAAGAAATCTGTTGTTAAAAAGGAAATGACTTTTAATGACT +ATAAGAACTGCTTATTAAATCATACTATTGAAAGAAGACAACAAATGTTA +ATTAACTCTAGCAGACATAATCTCCACAGTGTAAAACAAAATAAAGTTGT +GTTAAATAATCTAGTTGGTAAAGATAAAGAATCAAAAAGGTATACAGTAG +ATAATATAGACACTCTAGCTTTCGAGCATTATAGAATTCCTAAATCAGAG +TTAGAATAGAATTTTTATAATCatgtttttctaataattttaaTAAGAGT +AGACAGTAGTATCCACAATGATgagtatcaaatttttgtatttgaaacGT +TGAAGTAATTATTTCGTTTGAAGTATTATGTTTAAgatattttattattt +cttgAGGTGGGTCCAAACCAAAAGAgtcaaaataataatattcaCTTTTA +TTTACTTTATAACAGACCCAATGAGTACCTTTATTATCTGAACTATCAAG +ATTAATGATGCCTACTTCTACTTCTTTACGTTTTTCTGGTAAAGTATCCT +TCATAAATACACCTCTGAAATCTTTGATTTGTAACTCTTTTGCTATTTCT +AATAAATCTACATTTGTTAATGGTTTCAAATCTTTATTCAGCATTTAATA +AAACGTAATAATGGTaaagaattgaatgaaaagaGTGTTGGTTaacactt +gatttttttgtcgTTTCTTCATGGTTCTGAcggttgatttttttcatgtt +tgctcgacgagaatttttggctgatttttctgattttttcagtttttttc +atgattttttttcgttttttttcgattttttttcaatttttcttgcatat +ttttCGGATCTCATTAAGTGGATAATCCTGAGCTTTTGAGTGGGGTTCGA +ACTTTCTACCATTCAAACACAAGACAGACGCTTTACCATTCTGACATGAG +AACAAATTGATAAGAGAGTTGAAAACGCATTTAAGTGTAGAgaatttctt +atcagttgGGGTGAAAAGTGACTGTTTTGAGAGgttgaaaaaagtgggac +aAAAGTGGGAAAGTGAGTGGGGGTGAACTCAGTTCACCAAAATCTGAGAG +TGTGAAAATCGTGGATTTTGCTAAGAAtattatatgaaaaaaataattag +ggcaaaaaacttgaaaaaacagcaaaataaaaatttgaaaaaagtgggac +aaaaGCTGTCCCAGAAAGGACAATTCCCTACTACTCAAACCTCATTTGAC +AACTCCTGATTGAAGTACAAACGAAGCTGAGCGATGGTGTCGCTGAATGA +GGTTGGTGGAAAAGATGGAACCGATTCGCCTTGAGCGACGGTGCCGATTG +GATCAACGGGCAAcatctgaaagaaatttttgaatctcatcTAATCTGAC +TTCAAGTCAGATATGCAAATCTCATTTGACAACTCCTGATTGAAGTACAA +ACGAAGCTGAGCGATGGTGTCGCTGAATGAGGTTGGTGGAAAAGATGGAA +CCGATTCGCCTTGAGCGACTGTGCCGATTGGATCAACGGGCAGcatctga +aagaaatttttgaatctcatcTAATCTGACTTCAAGTCAGATATGCAAAC +CTCTTCTGCTATCTCCTCAGTTATGGACGACCGAGATGCCTCTTGCTCAT +TCGGTAGGGTCAATTGAATCGATTCGTCTGGATCGATTGGACTGATTGAA +ACTCccgacattttctgaaaaaaaaattggtgattagACAATGAAATGTG +ATGGGGATGGTGAGATCCAAATCTGACTTCAGGTCAGATCCAAATCTGAC +TTCAAgtcagattctgaagaattgACTTGAAGCCAATTCATTGAAATCTG +ACTTCAAGTCAAACCTCTTAATATATACAAACCTCATCTGACATGTCAGT +CTTCGATGAATGCGAGATTTCTTGAGCGGACTGGTCGATGGAATCATCCG +ACAACTTTTCTTCATCGAAGGGGGTGATCGATGTGATCGTTTCCTCGTGA +TGGGAGGTCTCTTGAGAGAGTTGAACGGTGGGAGTATCCGccatttgctg +aaaaaaaatttttgattagaCAATGAAATGGGACTGCATGAAACGTAAAG +AAATAGGATGTGAAGAGGATAGCGTGGAGGAGAATCTGACTTCAAGTCAG +ATTTTGAAGATATGAATGGTGTGAAGGTGAATGAATGGTGCggaggagca +aaaaaaaagaaacgaccTCCTCCCACCAAGACAAATGGCACGAATGACTG +GAAGGTAGCAGAAATGAcgagactccgcccctttacCGTATGatgggtct +caccacgaaaatGCGTATctaacttttaaaatattaCATGTTTCGAATTG +AAAGGCATCCAAATCTGACTTCAAGTCAGATTTCCGATATTTGACTTGAA +GccaattcttttaaaaaatttgaattcaagttAGTTAGGCACAAGttatt +actctcgtccgaaatcaatgcacgttgcggccgaaaatttactcaaaatc +gcagaTTTCTCAGCCGCCACGTGCATTGActtcggacaagagtaatagtT +AGGGCAAGTGAAATAAGTGACCTCTTGTTCCGCTGTTTCTTGATGATTTC +TGGCGGAAAGACGATGCAATGTGAGTAGCGCTTCCCGTTCTTCTACTTTG +GTAATGTCCACAACTTCCAGCTCCGTTTCTTCGTTGAAGAAGGTCACGTG +ATAACAGGAGAGCAGCTTCACATCCGACTTCCACAACACTATTTCATCGG +CGTTTTTGAGTCTTCTCTCAGcaatcaacattttctttcCGTTCAGTACA +ATCTGAAAACATCACAATTAAATACCAATTCGGGGATCCTCTAGannnnn +nnnnnnnnnnnnnnnnnnnnnnaaTGACTGAAGCAGAGCAGAAATGGCAA +GTCTCCGCCCCTTTACCGTATGatgggtctcaccacgaaaacGCGTATCT +AACTAATAACTGACGTGGCGCCTAAAATCAGattcaaactacaaattttg +agttgagctgaaatttcgagttgAACTGAAATATCGAGTTGACTTGTTAT +ATTCATTGAAAAGCAATCATAGCCGTTGCTAGCGCCTCTTGAAATCTGAC +TTCAAGTCAgaattgaaaacttaaaatcatATCCTCATCTGGCAAATCAT +CAGTCGTCGACGAACGcgagttctttttttcataaacaGGTTGAGAACAG +AACacaagaattaaaaaatataatttattgaaatggGGTTAGTAAAGTTC +TACAATtaagttgaaaaacaaaaacaaaaacagttccatacagaaaagtt +gggttagaaaaaacgataaagaagaaactgaaattcgtGGTTGTTTTCTT +GCGTGGTTGTTTTCCTAAGCTCATCGCTCATCAATTTCCGCTGGATTTTC +GGTCCTTGTAGAGGATGTAGGCTTCGATGGCGGATTTCAGAAGATGACGT +GGCTTGATGGGGTGTTTGATGGTTGTTATGCgggattcctgaaaatgaga +aatttgagatttaaggattactgtaaatgtCTTTATTTcaaaggttactg +tatttttttttgaatcaaaagaaaaaatcaatattttttcatgaaaaatg +atcaatgatgatgatttaaaaactttcatgagaaaaattaaagatttttt +ttccaattttttttcagaattttcaattatttatgAATCTTCTTACCATG +ATCCATTTGAcacactttttgtttttgagaaagttctTTGTTAAATCACT +CGCCAATGGATTTGCCAACTCGAATTCCAGAACGGCTTCGTATCgttttt +tgtctggaatttttttttggaaaaaaaacagctaCGCTTAGGCTCAGGCG +CAGGCGTAGCCTGCGCTATTTGGGCTGAGGTCGGAGGggtgaaattggaa +ttttcaagtttttttttcaccattgGATAGagcatcgaaaaaaaaaggga +cATACTATCCTTAGTTTTTCACCTAAGGGCACCGTTGCCGCGCTATGACG +GTccaaagtcaaaatttcaaaattttctttttaatatAACTTTTGAACGG +ATTAATTTTATGAATTCGGAGTTTGACCATTCGATGCGTCTTTGGAAGGC +GCAtttttttAAcaagacaaaattttttttttggaccccccgacccccGA +AAAGTcgattttaaactttcaaattgaCCGTTTAGCTACACCTTCTATac +gaatttcctaatttttttactgaagGTCCGCCTTGGGCTTGCGCGTTTTT +TAAGTATAGTATGTGAACACATATAATTGTGGGAAAGtccccaaattttg +aaaaaaccggtttttggtttcttttctCACTCTTCTATAATTTCTATGAA +AGTTAACATACTCCACTTCTATTTTAGTCAGATTTTTCGGACTTAGTTTC +ATTACTGAAACTAAAACATGATTTGGGCTGCTGGATCGACCTATGAAAGT +TAATAGACCGCTCGCTTCGCTCGCAAGATAATCCTATGAAACCACCTGTT +ATTAAGTAATAAGCAACAATTTAGAAAATGGtcgttaaaaaaattttcaa +aaaaaaaattttcaaaaaaaaaaattttcaaaaaaaaaattttcaataaa +aaatttttttttcaaaatttcaaaaaccctaaaaatacttaaaaaCACTT +AATTTACACTCAGGGACCCCTACAGTactcgaaaaaatggaaaaaaaaat +tagtgcCACAGGCGGGTTCCTCGGACCGAAGGTGAAATTTTGGACACACT +TCCCAACATTTCCTATCCATGATGCAAAAATCAGAACATGTTTATCTCTT +TTCTCAACTGAGTTATTACACGTCAAACAGTGGTGCGCGCTCGTCAAACA +GTGCAAAGCCACAGTACATTAAAACTTAAAACGACCGTAACTTGCGTCAA +AATGGTTGTAGAGGGATGGTaaaaaaaCGAATCGATCAATGAACTCTACA +TTTTTGTTCCCCTTCATCTATACCCTATCTTTACGTTTAAGACctcaaaa +ttgccaaaaacctcgaaaaaatGACGTTTTTTGTGTTTGACCGACTGTAG +CTCGAAAACGAACCGTTTAACATATTGTTTTAAAACCTTAAATCgagcta +tttttcaatttccaatcgATTAAAAGTGGTCCGAAAAGGATTCTATAGAC +AGTTTTTTagcagtttttttcaaacggCCATATCACACCCGGGTGGTcac +aaaagtgaaaattttttttgcccaTGATTTAAACCTCATTATGTACTACA +ACTTTCCTTCTGTCGGTACCATGCCGCCTCTGACCGTTAACGAGATATGG +ACCCCAAAAaccggttttttcaaaatttggggaCTTTCCCACAATTATAT +GTGTTCACATACTATACTTAAAAAACGCGCAAGCCCAAGGCGGACcttca +gtaaaaaaattaggaaattcgtATAGAAGGTGTAGCTAAACGGtcaattt +gaaagtttaaaatcgACTTTTCgggggtcggggggtccaaaaaaaaaatt +ttgtcttgTTaaaaaaaTGCGCCTTCCAAAGACGCATCGAATGGTCAAAC +TCCGAATTCATAAAATTAATCCGTTCAAAAGTTatattaaaaagaaaatt +ttgaaattttgactttggACCGTCATAGCGACGGTGCCCTTAGGTGAAAA +ACTAAGGATAGTATGTCCCtttttttCGATGCTCTATCcaatggtgaaaa +aaaaacttgaaaattccaatttcaccCCTCCGACCTCAGCCCAAATAGCG +CAGGCTACGCCTGCGCCTGAGCCTAAGCgtagctgtttttttttccaaaa +aaaaattccagacaaaaatCGATACGAAGCCGTTCTGGAATTCGAGTTGG +CAAATCCATTGGCGAGTGATTTAACAAagaactttctcaaaaacaaaaag +tgtgTCAAATGGATCATGGTAAGAAGATTcataaataattgaaaattctg +aaaaaaaattgaaaaataatctttaatttttctcatgaaagtttttaaat +catcatcattgatcatttttcatgaaaaaatattgattttttcttttgat +tcaaaaaaaaatacagtaacctttgAAATAAAGacatttacagtaatcct +taaatctcaaatttctcattttcaggaatcccGCATAACAACCATCAAAC +ACCCCATCAAGCCACGTCATCTTCTGAAATCCGCCATCGAAGCCTACATC +CTCTACAAGGACCGAAAATCCagcggaaatttcaaatttcccgccaaact +CCACCCGCTCATCGCCACCACGCCTTCAGGCATCATTCAGGAGacgttat +caaaaattttggatccagaaaattctgaatatttatCACTGAAGAAGGCA +AAAAAGAGAGTGGAAAACGCGTCGGGAATGAAGATTCTAGTGGAATTGAC +GTCGAATCAGAAGGCGATTCAGatgaaggattctgaagacgtggaggatt +cagaagacgaagaagacgttgacatcgaacgtcttctaaaatattctaga +aaaatttcacgTGAAATAGacgaaaagaggaaaatagaAATGGATGAGAT +ACTGGAAAAAGCAGATCCCGAGAAAATTTGgttaaaaatgtctgaaaatt +cggaaaacttgGAGATGAACGAAGacatgatgaagaagaagacgtcgctg +aagaaaatcgccaaaaagcagaagaaaaatgtgagaaatcgatcgaaaaa +attggtggAGGCGTCAGATGATTCAGATCAAGATGGCGTGATCTGTTTAG +AAGacacttcagaagacgtgaagaATAAAGATCCCGCGAagtccaaaaat +aaaaaaaggaaggatCCAGAAGAGTTCCCAGAAGacatttcaaattctga +atccaaaaaatctgaaaaaagaaaacgtcGAAGTACAAAAGACGTGACGG +ATTCTGAATCCAAATTTActaaaacgaagaagaagaagaagacttcTGAT +GACGTGCCAACTTCGGAAGACTTAACCGGGAGACGTGGCGGATTCTGAAT +GTGAAAAGTGGATAAAAGAGGAGTCAGTTGACGTGGCGGATTCTGAATGG +ACgaaagtgacaaaaaagaagaaggagaattctgaagacgtgcCAACTTC +AGGAGACTTTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +NNNNNNNNNNNGTCATTTATCTAGTAATGAACACCTTTCGTATAATAGTA +TTTATAGTGCAATGGCCtatgattccaaaaatgaagaCCTAGGATCAGAC +AAATTGGAATCCTACAACTGGAAAACGTGGCGCTATGTATCCGACAAATC +CGGTATATTAGAGTTATACTGTGTGACGGCCTAGAGTCCAAAACCGATGG +CCTAGGATTCAAGACCTCACTTTCTAAACTGAAATTCATCAGGGTACTGT +ACCCGAAATTCAGAGACAGAGAGTTTTAATTGAAttgttccgaaaaaaat +gtcCGAATTTCCCATGCTGGGACACTTCAAATTTCCTTTTCAGCAGAGGG +GGGCTCTGGAGAACTTGGGtgaaattggggaaaaaatattaaaaataggT +CCCCAAATTCCCATTTTGAAGGGGAAgcgaaaattgggaaattccgCTTT +TGAAAGAGGGAAACTtgcaattccaaaaaaaaatttttagactaaaaaac +atttattacCATTTCAGAtgatttgagctcaatttgtGGTCCGttttgaa +aaaggaatttcagatttttttttggaaatttttgatattcctggaatttg +aaacaacttaaaaaaccgaaaattcaaaaaaaaattaaaaactcgaaaca +tatagtttgtagtctttgtagtcccttcaaaaatcttatagttagtctaa +aaaaaatacaaatttccttctttttggtCCCATTTTCGGCCCCTAAATTT +ATCCATTTTCCACCCAATTTTACGACCTTCGGAAGTCAATTCTCAACCat +tttctcttctatttcacaaccttttattttcgatttttcgcttttttttt +tgttttttgaaaattgttcacatggacaattttgcttttttcccccattt +tttcccaataaaaatttccattttaaGTACATaatttgagtgaaaaattg +agatttttcaggattttagaattttaggaatttctgaatttcagaaaaaa +atgctgaaaaagaaaTGTAGAGTTTTCAAGAATCCTCAAAAAGTCTCAAA +TCCTAGGCCATCTCTTTTGGGCTTCTAGGCCATCATAATAATAGGCCATC +ATAATTAACAAAGTAAATCTAGACTTCCGGTTTTATGGATCCTAGGCCac +gttttccaattttaggtCTCTTGGATTCTAGGTCATGTACATCCCAGTAC +CAATCCTAGGCCATTGCTTTTAAGATTCTAGACCATTGTCGGATCCGAGG +CCATGACGATTGAACTGAAATATAAAACTCTTTCTAGGATTAGAAATTAC +CGTAATCCATAACCggaactaaaattttttgaaaatccgtggttttcgaa +aaattccaatttctcagAAAAGTCATAAAGTTCTATGGGTAATAAATCTT +TATTTTCTTGGGGCAATTTTTGAGGTAAACATAGTAATTAAGTAATAAAT +GTGGGTgaaagattacggtagatctCCAATtagaggattacggtagaccG +GAGTTCTATAGAAACCCTGTAAAACCAGCAATTCTTCAAATCAATTTATT +ttggttcttgtgaaagatatcaaaatgtgaccaactaataaaatattgcg +ttttttatgatgaacattttattagttgattacttttttataacttttac +attaaccgagataaatcctGTTGAAGTTTACGCTATGAGGACCCTTGGAG +ACCGCCATTGGAACCGTTTACTTCAAGCCAatatatctcgcttcctgtaa +gagatatcaaaaagtggtcaactatcaaaatattgatccgttcttgataa +acattttgtcagttattaactttttgatttctcttacagtaaccgagata +aatttagTTAAAGTTGACGCAATATAGGACTTTTCTATCGCAGCTTTTac +catgaaattttttctaccCTCATGACAATATTTCAATCCCATTTGAATGC +ATATAATATTACTTTTTGTCCCTTTTCTTtatttggaccaaaaaaatttt +gtctgaTGAGACCACaagaaaaataacaagaatcatcattttcagacaat +tcaagttctgaaaattattttttcactaaaaatttcaaaattttcgatga +cgtgcattccagaattttttttctagaattcacAGTAATTAGATCCTGCT +GACTTTCCCATCGAACCAACGTCAATCAGGCcttctgacattttcagaag +gaataattttcggatttcaaaaaatttgtttttttatttttatttttgtt +ctcTTGTACCCTAAATAAAAACTATTGTAAtccctttgaaaatttgaatt +tttaagtaccgaaacccatttttctaattttttagaacatttcCTATTAC +CCcgaaattctccaaattttcccCCAGTGAcctctcctcctcctcgactc +ccaccgtgccccctttcctgtacgacctccctccctttctcctTCGGGGC +CTCCTTAGCTCAACAGAAAACGaaannnnnnnnnnGAAGGTGGTACATAA +CTTGTTGCATTGTTTGCAAATCCTCATCTGAtcttatcaaattttttcat +aatctcTTCCTAAAACCtttttgctaatattggtattttttgctcttatt +aatatttttccttttttttcgatatatcAAATGTCGTTGattgacgtcat +ctgaatgaCATAggttgacccattttttggTTCATGTAAActacttttcc +aaaaaaggcttaaaccatcgaaaaactccctgaaaactaatgaaaactaa +tgaaaacacaaaaacaaaacttaaaaaaaatcaagccACCTAGGGGACTC +GAACCCCTGACCTTAAGATTAAAAGTCTCACGCTCTACCAACTGAGCTAA +GGAGGACACGTAGCACAATGTGGGAGTGCGTACAAGAGGGCGCGCCCTCT +CGTTACTTTTAAGTTCCCCGTGAAGGTATTTGGGtggattcaaaaatcaa +aaaaatccaatcaaaataaaaaaaggaattgtCTCAttcaaaagagagaa +aattggtttttccaGGGAAATATATGATGAAAATgtatcagaatttgaaa +tgtATCAGAACGGAGAAAATGTATCAGAATGGAGAATTGTGTAGCGTTTA +GTACCCAGACAGAGGtataaaaatttatattctagacatttcttttttgt +tgaaattcgcagaaaattggatttttcagaatggagAAGAAACCACTTTG +aggtttgaaaattaaaattttcaaaaatttagaaatttcaaaaatttaga +attttcgagaactctaaatttcgagaaatttctgaaattcagaaattcag +aaattcagaaattcagaaattcagaaattcagaaattcagaaattcagta +attcagaaattcagaaattcagaaattcagaaattcagaaattcagaaat +tcagaaattcagaaattcagaaattcagaaattcagaaattcagaaattc +agaaattcagaaattcagaaattcagaaattcagaaattcagaaattcag +aaattcagaaattcagaaattcagaaattcagaaattaagaaattcagaa +attcagaaattcataaattcagaaattcggaaattcagaagttcagaaat +tcagaaattcagaaattcagaaattcagaaattcagaaattcagaaattc +agaaattcagaaattcagaaattcagccattcagaaatgcggaaatccag +aaattcagaaattcagaaattcggaaattcagaaatccagaattccagaa +attcagaannnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnttcagaaattcggaaattcaaaaattcagaaact +ctaaaactcctaggtcaaaaaGTCCAActaaatcaaatttttggaatctt +ctagaaactccaaaaaaattttgtacccaaaaacattttttcttctgatt +tcctTGTATTCTAGAATCTCTGtctagaattccaaattctcatttttccc +acGTTTCGTCTCTGATTGCTCATTACTCATTACTCATTCACAGTTCTCAG +ATTTcttagctccgcccacttttctctctctctctctctctctctctctc +tctgtctctctctctctctctctctctctctctctctctctctctctctc +tctctctctctctctctctctctctctctctctctctctctctctctctc +tctctctctctctctctctctctctctctctctctctctctctctctctc +tctgtctctctctctctctctctcacacaatcaatctctctcactctgcg +tctccctctctctAACTTTGATTTATAGACTCCTTCCAAGTCTCTtaaga +ctccgcccacttcgcCGCGAAACTTTtcggctccgcccactttcgaGAGC +AGCTCCACTTCTTCGACGGCGAGCTCTCATTCCATTTCTCCTCCACACAG +AGTCTTGACGTTCTTCCCAAGTACTCTGAAAGCAGCAAATATGCTTCACC +GAACTGTCTATTTGGCTCTTTTGGCCCTCATCGTCGTCTCGGCCACGGCC +TCGGCCATCAGTCTTGAGCAAGCCGgtcagttttgaaaagttttgttaTG +AGAAGGCTATTTAATCTAGAAGggcattttctcaaaataccgTTGTGTTC +AATAGAGCGCTCTTGCCGAAATTCGCTGTATTGTCAGCAGGGCGCGGTTG +CGCGCGGCGCCAATAGTATTGCTTGGAAAAATCAggtttttatcgatttt +ttttgccattttgacATGATTTTCTTGTCTAGAAAATGATTTAAAGGCca +aaacacacattttgagtacaaaagactgaaaaattacagaaaaatcgaat +ttttgaattttttgaaaacaattttttatttgaaaatttcgattttttgc +catttcgacatgatttcctcatatattttgattgCTAACACATCCATGAC +ATGAaagctgaaaactttgaattttttgaaaaaaaattttttgaaatttt +aaaattttttaatttaatatttttaagatttcccaaatatttcgaatttc +aggatttttgtagTCTCTAGGAACCTggaattttcactgaaatttttaag +ctccgtgagaaaaaaaaatcacaacttttcaaaaaaaataattatttaat +taaaacaaagggctttcaaaaaGGTTGTGGGAGTCGTTTTCATTTTGCCC +TTTTTGACGAAAACTCCTATACTGAATTATGTGTTAATTGCCTCCATTCt +agaggaaaaaaatttcaatgggTACATAATCCATTTGagataaattcaaa +atgttgagTTCAAAGGGAGTTATGGAGCTTGAAGTGAGCTAAGCGCTAAT +CTACCAACATGGAATTATACCTAGATTGTGTTTTGATTCGCCTGCAAGCT +AGCATTGATCAAAATTAATAATGTATAATATTAATCTGTAGCTCTTGTCC +AGGGCTACATTTAACATTTtgattcatcaaaaaatattaggtTCGACGAC +ATATATGagcaaaaaaccaaaagtagCAGCGATCTAGACTTTCGCACCTT +CTGCTTGAAATAGGGCTAGATTCACATAGTTAATGCTTAGTATTATTTTA +CAGCTCTATCCAAGAGCTACAAGATACAAGTTAAATCAATAAAAACTATT +GAGTTTGAAACGagttataatcaaaaaacctaGGGTGTAGTGGTGGTGGT +AGTATAGCGAGCTAGAGATCTTGTAGTTTGTACCCTCCTGCTTAGTACAA +GAACGgaaattttgtaaataatATTTGATGGTTCTGTAGAACTTTTCAAG +CGCTACACGAcacactttgaatttttcaaaaattctaattttgaagcgag +ttataagCATAAATGCTAGAGTGTAGTGGTGGGGTAGTCTAGCTAGCTAG +AGAACTTGTAGTTTTGACTGTCCTGCTGGGCATTAGGGATGAGTTGGCAT +AGTTGATATTTATACCAATTTGTAGCTCTTTTTAAGGGCTACAAGATACA +AATTGAGCTACTGCCAAAATCTGATTGCGAAGCTAGTTTTAAGCAATTCA +CTAAGCCAGCCCCTCAATATCAGGCATCCCACTGACTGCGGCATCATAGC +TCCCAGACTTCGCTGTTGACATAGTTGATATTAATATCAATTTGTAGCTC +TTTTTAAGGGCTACAAGATacattttgaattgtttcaaaattatattttt +gaagcaagttataaGAGATTTTCTGAGCTtaaccttctttttttaaattc +aaatttcccgccaaatccTCTTCTTCCCATATTTCCTCCAAGTCAACAAG +GAATTCATATGAATAGTATAGATCCATGCTTCTCAGAACTTTCTagagac +aaaaagaaaagttttatGGCTCTTCCCATGGCTCCGAACCAATAAAAACA +AGACTCTCCGACTTTTTGATGACGTGGCGAAgggcgaaaaaaagagacaa +ggAACCCAAAAATATGTGGaaaaaaaTAAGCATGAgcgatctggaaattt +gagaaaaaacggcCTAGGAATGATGTCATATAAGGAATtataagaaaatg +tttttctttaaaaaaaatagaaagttccagaaaaatggggaaaaatggca +aaaGGGAGGCGCTCAGGCTCTTTCGtgtcccaaaaaattaaaaattctga +acaaaataaaaGTTCCCATAGCAACTATTGTGCTCTTCTAAGAGCCAGAA +GAAACACACAAGAAaggaaaaacctgaaaaattaatattttcagacggCC +GAATGAAGATGTGCCCTCCCGGGGGCTCTACCTTCACCATGGCCTGGAGC +ATGTCGTGCTCGATGCGCCGGAAACGCGACGTCTCCGCCGATGACTACTA +CGGAGGCATTGGTGAGTataattttgcatttttaatATGCTCAGGAGATC +AGGCATAGTCGAAAACCCATtgtcacaaaaaaaaccagagaGAAAAACCT +ATCGTACCGCCCAGGGGAGTCGAACCAAGAACCCTCTTCGGCTCCAAAGT +CACCACCACTAGCCACTACACCACACTAGTGTGGGCGTCCAACCACTGTT +GCGTGGCGCCTCGCCACCCACCGCGCCCTTATAAACCAAACCAATTGTCG +GCATAGCCCGCCCCCCATAGCCTAGTGGTTAGTGACGCCGCCCTTGAAGC +AGGGACTTGTTGGTTCGACTCCCCTGGGCGACccgttgatttttaatttt +ttgctttattcTACAAGGTGAATCAAGATCGCTTTATTCGATAGAAGCAA +TataatttgtgattttttttcagccaaacgCGCCCTGATCGCTCCATCGA +TCCGTCAGCTCCAAACAATCTGCTGCCAGGTCGGCTGTAATGTGGAGGAC +CTCCTCGCCTACTGTGCACCAATCTAgtaggccacgcccccttgTTTCCA +TCTTCACTTCTTCAATTCCACTGTATTTGTACTTTTCCACACCAACATGA +GCCATCATCCCACCCCCAGACACcgtcaatttccaaaaaaaaaaccaaac +atcTTCATCTTCCCTTTCTTCGTAATTTATCTTTTTGTCCTGTCGTCATC +AATTGTTTCCACGAAAATTCCACCTGAATGAATCAAGCTGTTAAAGAAag +tattttttagaattttcagtttttcagggagaccagaaaaatgatttcaa +aaatatttaggattaatttttaaaaaaaatatatattacAGAAAAACGCA +CAAATAGgggaaaaatgcaaatgcgctctattggacaCGAAGTTCaaaat +ggagcgcattttcaacgaaatttccaaaaataacgTAAAGAGAGATATct +agaagaaaatgagaattttcggaaacttttttgaaaaattaaaaaaattt +tttttgggaatttcgaaaaattaaaggGACACACATATTATGCAGATTTG +TGAGCAGATGAGATTCGGGGTGGTGGTCagaaaattgtacaaaaagaGGA +AGGTtaggcgggaaattcgaattttggggATAgtaaatttagagaaaaaa +aagaaaacatcaagtttttggataaaaaaatttcgaataaaaaggcggga +aatgcaaatttctgaaaatttgaaaattaataaaaaattagtaaaaaaac +ggagaaattTAGAGTAGAAGCGAAGCGTCGTCACGGGGCAGCAGCTTGAA +TGGGTCGCCGTCGAaccactgaaaataaaaatgtttattgaGAGAATCTG +GATAAACAGACACACAGctggatttattttttgtgggaacaaatttgaga +atttgttttctagcgaagtggtggcctagaaaagcaacattgcaaaagtt +aggccaccacttcaaaatggcctaaaaatgacctgacatgaccctggtgt +gttttctaggccattttgaagtggtggcctaacttttgcaatgttgcttt +tctaggccaccacttcgctagaaaacaaattctcaaatttgttcccacaa +aaaataaatccagCTGTGTGTCTGTTTATCCAGATTCTnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnGTACGAGAAATAGGCGTGAAG +GAGCTTGACGTTGCTCTTCAGCATCTGTGAGCATCCCGCGATTTTTGGGG +CTGTTAGTctgaagaaaagagagaatttAGAAAGTTTTTCGGCTAATTAA +ATTTTCCTCACCTCTCAGCGACTTCATAATAATCCgccattttcaactga +ttcaAATACGTCcatgccaaattcaaattgatgaaAGCAATCTTATTATG +CGACATGGTGTCGTCTGGATTAATGAAATTCAGCGCCGAGACGAAATGCT +TCTCCGCGTAGTCGTATTGATGGAAATAACAACATTGGAGaccctggaaa +tttgaaatttttacagttaaattgaaaaaaaaattaggtaaaaGTTAGCT +TGAAAAAGTGCCATTGAAATATACCCTTTTTTAACGGACGGAAGTTTCCT +AGTCCACGGCCACCATAGTCTTCTTCAGCTCCAATATTTTGGAACCAACT +GAATTGAGTATGGTAGAAAAACTCAAGAGCtccaaaatgatactatttgg +attactgtaccttgtcAATGAACAAAGTCAGCAAGCCAATAAGCAGTGAT +CGCTTAGCTCGTTTGGTTTTTGATTTGTAACTtcgttcatagacaagata +taGTATCCATAAATAGCTTCGTTATGTAGCTCATGAGtggaaaattgtca +aaaaattattgaaaaatgtccataattcataggaaaatgatccaaaattc +atgaaaaatggtccaaaatttacggaaaatggctcaaaattcatgagaat +ggcttaaaatttgtgaaaaatggtcaaaaattgatatatagtccaaaagt +catcaaaaactgccaaaatttatgaaaaatgactcaaaatccatcaaaat +tgtccaaaattcatgaaaaatggtccaaatttcttggaaaacggtaaaaa +atacattttttaaaaacccaccaaaatATACTGAATATGTGGTGCATAGA +ATCGATACAACAGCGGTCCACTGGATCGATTACACATCTCCAGCATATCC +CGAACATTCGACAGTGTCTGTTCTGGTCGACACGCCATCACATTACAGCA +AGCCATCATCTCCAACGTCGTCATTTTGATCATATTGATACATCGAACGA +CACCCGGCTCCTGNGGTGTTCGTGTGTACTTGTAGATGGCGTCATCCGCA +TGTTTCACGActaaattgaaatatttctcCAGTCGACCCGGATTCGATTG +AACCAACGCTGAGGTGATGTTCATTACGCATGCGAACAGGGTCATCGACG +CTTCGCCCAGCCATCTGnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnaTTACGCCAGCTGGCGAAAGGGGGATGTG +CTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGT +TGTAAAACGACGGCCAGTGCCAAGCTTGCATGCCTGCAGGTCGACTCTAG +AGGATCCCCTCAAATCCGTCAAAAAATCTTGTTCTGAAGCCGAGTTATCT +GCCGGCCCGCCATCTGCCCGGGTCGGCCCGTTTGCAAATATGGTCTAAAA +TAATTATAAAGGGTCAAAAACTATCCGAGAATggtcaaaaagtgatcaaa +aatccatcgaaaattgtgaaaaggaactcaaaaatggacgaaaagtgctc +aaaatcagtcaaaaataggcccaaaatgatccaaaaatttttcaaaaacg +ggtaaaaaataggttttttggctgatttttgaccatttttgattgctttt +cgagcatttctcacaatttcagactattttgtctgattttttgcaatttt +gacaacttttaaaactgattttagaccattttgactgatttttaaccgtt +tttcataccatttttgactgaattttcgtcgttttatgaccgattttttt +tcgtttttcagctgatttttgatcatttttgactgattttagACTAATTC +TAAGTCAAAAAGGGCcgaaaaatggtccgaaataaGTCAAATTGACCCAA +AGTGGGTCACAAATTAGtctaaaatggtctagaaatggccgaaaatccaT +CAAATATCGTGTaaaaggaggtcaaaaatggacgaaaagtgctcaaaatc +agtcaaaaataggttcaaaatgatccaaaaatgtttcgcaaaagggtaaa +aactagttttttggctgatttttgaccatttttgattgattttggagcat +ttttctcaatttccgactattttgtctgattttttgcaattttgacggac +tttttAACATTACTAGGACCAATTTCGGCTGATTTTAGACagtttttaag +ccaaaaaggGTCCGAAAGTGgtccaaaatcagtcaaattaacccaaaatt +cgtcaaaaattagtcaaaaatggtccaaaattggtcGAATTTGGCCGCga +atagctttaaaaattaGTCAGAATATTCGGgttaaaatggtcaaaaattc +attgaaattgattttttaatgggTCTAAAATGACTCAACAGTGGTCAAAA +ATAGGTCAGAAATTGTCTAAAATCACTATTGGACCAAATTTTGCGCCtta +ttttggaccaatttcaatcaattttgacggaattttgaccactttttaac +CAATTTCTCACAATTCCACCCTACCTGATCCCCTGAATTGTCGTCTCTCC +ACTCGTCTGTTGCTTTTGAATTTGTCTCAAAAGTTGTCTGGACGTTCGCG +ATTTGCCTTGATAAAACATGTAGGCCAGCTTTGTACAAACGAAAAAATCT +TTGATCACTTCCAGATGAGCCTTGTCTGCTGGATCCGCTTCCAGTGCTAA +AAACTGGTGATTTAGATGGATTTTAGTGACGAAAAAggtcaattttaggc +caaaattagctcatttttcgtcggattttcgaccattttcaccAATTTCG +GATCATTTTGACTGTTTTCTGACTCGTTTTAGACCCAGTAAtgaattttt +gaccattttaacCCGAATTCAgactattttttaaagctatACGCGACCAA +ATTCAACTAGttttggtgtattttttgacctatttttacgatttccaacc +atttttgcgcaaaattagcactatttttgaaacttttcgacTAATTTTTT +GGTTCATGTTGGGCTAGTTTCtgactcattttcagccattttcaattttc +agccattttttaaggattaatttcagcagttgattttcTGTCAAAATTCA +TCGATTCTGGAgatttttaaactcaattttcagcatgttGAAGCCATTTT +CCcgtattttcagccaattttcagccatttcacggtatttttttgctatt +tcaaATGTCGTTTTGGCCGTTTTTAGATTGATTTTAACCAATTTCAGCTT +CATTTCCTATCAGTTAGCTTAGCTTAAAACTGACTGATTCCGGTGATTTT +TAGCactttttagctcaatttctagcgtttttcagctatttcgagcccat +tttcaatgattttcctGCTCACCCTTAATCAATTGTCCAATTTTGAGCAC +ATCCTCGTTGGGCGGCTCCTCGTGCATCAATTGATATGTCACCAACGTTT +TCGTGATTCGAAAGTATAATTCCATTTTGGCGTTGTTCGCAGCGGCGCTT +TGTGCGATGCCATAGTGACACATATCGAATGCGCCGTCCGAGTCGTTGTC +gattttgttgatttcctGGAAGAGAGAAATtgggagttttctaggccagc +aagagttatggcctagttttgaaggtttttaGGCCATTGGGGAGActtgt +ggcctaacttttttctaggccatcttaTAGGACCCTACCTGGAAGAGGTA +TGCCTAGGTTGaaggtttctaggccagctaAGAACTGTGGCCCAACTTTT +GCAATCatcattttctaggccatttttgaggaatttcgattttctaagTC +AGCTAAGTTTTCATGAGaaccattttgaagtggtggcctagaaaaccaaa +ttgtcgaaagttaggccaccacttgaAAATGACTTAggaaacacaccagg +gtcatgAGCATTGTGGATTAATTAAGATCTCTAGGCCAACTTCTtgtgtg +gcctaacttttccattttgctattttctaggccacccctTTTCTAAATGG +cctaaattttgagatttctgaatttctaggccatttccgacatttctagg +ccatcaggtATCTTTCGGAGGCCATTTTTGAGGTTTCCATGCCAGAaatt +ttggtggcctaactttcttatttttcgattttctaggccatctccATTTT +ACTGGAAGagggtttctaggccaatttttttggatgacctaacttttgag +atttatgagtttctaggccatttaagacatttctaggccatcaggcTTCT +TTCTAAGGCAATTTTTATGTGGTTTCTATATCAAAACTTCACGTGGCCTA +ACTGTTTTATTTgcgattttctaggccacaccATTtctgtggcctaactt +ttgagatttatggatttctaggcagtttctcgattttctaaGCCACCCTT +ACAATCAATTGAAACAGGAGCTTATTGGTGAGCGTCTGGAATCCACGTGT +ATGCAGAATCTCGTGTTTTAGCGCGTCTTTAATCGGTCGAGCCGGCCagt +tttggtctgaaaattgaaatttttgtaaatctgTGCATCCGGATGTCCTT +ACAGTGAATATAAAGATCGGCAATCATCGAAATAGCGTGCATTCGCTCCC +GAGCAGCGAAATCGCCCATTTGTGTCATTTTGTCGtactggaaattgaaa +attttgaatattatgGTGTTCTGGaccaattttagaccatttttaaaCCG +TTTTAAACCTATTTAACTCACCGCCAACTGCAAATGATTGCGGGCTAGGT +CGAAATTCTCTGTAtagaaaaagagcaattttCCGAGCTGCAAATTGCAT +CGAGCCCTCGTTTCGTCGTTTGTGTCCAGTTTTACAGcgctctggaattt +ttttccgggtcatttttgtgtatttttggaattttttgaccgattttgac +attttttgagcaaaatcggaaaaaaaattttttccgaattttcaaaattt +tccagattttcagctctcttttctcatttttctttaattttcgacaattt +ttcatttcaatttcagctcaCTCTTGCACATTTAATAgccattttgagtt +ttggcgGGTCCTGAGTTCTCAGCGCTTCCGCCATGCCCAACAGCGCCTTC +GCCACTTCATCCTGGttcattttcctgaaatttttgatacaaaattttaa +ttttttcaagtttttagcgGAAATTGCACTCAAAACAGactaaatttcaa +atctggCGGTGGCTGAATCGACTTGGAAACCGCGGTGGAAATGTCAGcga +tgcaagcgcgctccgtTGAGAAAGCGAAATTATTTTATTGGAAAACAGGG +AAAAGATAGATTTTCTTCGGTAATTTGTGATTTATGCGATTCGAAAGGTT +GAAAATCGTGTTtagcaaaaaaatccaaaccaAATGACATGTAAAACTTT +GCAAAATAATCAACTAGGCgctgagaaattgaaaaaattgcatttgaaaa +atgatctttttcggattttcttttatttgtATAGGATTTCAGctatgaaa +attggaaattttcaattttcaggatacACATAAACActaaaatatcgatt +ttcctGCTGAAAAGTTAACAAAATAAGTTTCCCATCACATTGGAAATCAC +ATAAATCTTGCTTAAACTTTACTTTCGCACtagcgaaaaaattgaggaaa +aaaagatggaaaattgtctatttttcactgcatttccgcttttttaatct +tctcgatcccatggattttttcgtccttttttccttttttgagctTGTGT +CCCAAGCCTTGGGGATGGGAGAAAAGGGGAataaaataggtttttttgat +gaaaaaaaaaacaaaaacagtgATTAATTTTACAATGTTTGAATTTATTA +ATATGGAATAAAAGTTTTCCAATAAGATTCAAAGCATGTTTCCAgcaaag +aaacgaaaaaaagcaaGTTATACTCAAAAACAGGCCTTCAAACttcgacc +caatttatctcggttcctgtgaaaggaagcagaaagtggtaaactaacaa +aatgtttttgataatatgataaacattttattagttgaccacttttttgt +gcctcttacagggaccgagaaaagtcggctcaaagttgagggtaAGGTTT +TTCAGTGTTTCGGCTGAACATCCTTTGTTATGTAAATAAAGCTCTTTAGA +ACAATTGCCTTTGAagatgttttatttttcaaaaaactagaaaaattgat +tagaATACAAGATGAGAAGACAGTAGAAATTCAACATTCTTATAGTTTGA +GCACTTCCATTTTCAGTGACCATTGATTTCTGTTAATAGATTGATGGAAT +ATTGGATCACCATAGGAGACGAATAGTATGGAGGATGGACCAATTGACAG +TTTGatagatctgaaaatatcggTTGTTGGAAAACTGGCAATatcaaacg +cgctctaatggAAGAAGCATATCTCGCctcaaacttggaatttctcagcg +aatcaaaatttgaactgtACCTACGATCCGATTCGATAACTTGAGCATTT +CCTCTTAGAATATCTATATACCGCAACGGTTCCTCTCCTTGAAAGGGAAG +CCCTTGAACTTCAAACGACCAACTCGTCCCAACTGGTCTTCCGTTTTCCA +GCCAAAGGCTCATTAAGCGAGCAAAGCGGTTTTCAGGAATCCGAAACATG +cgaacttttaaatttgaaactctCATAAGTTGATCTATATGACAAATATA +CCCTCCCGAATATAGATGCAGTTTTTCAGTATTCACCACAATTTCGTGat +ccaaatttctgagatttacTGCACAGCAGAGGCTTTTCAAGGGGAAACTG +GTTGGATGACATATCGATCGAAGACCATCCAAATTGACAGAATCATAACC +CATCACTTGTAAATTTCGAGCTAATGGCTTTACTCCGGACGCAATCCAAC +GAAGGTTGCCAGCCGATATAAACATGGATTCTACATTCCAAATCACTGAT +CGATTTCCAAATATCACACCAATCAGCATTTTCATTCCTTCAtaaatttt +aatgatttttgaacttttgtaAATCCTTGGCTCTCCATTTTCAGGTTTGA +TTGTCAATTTCAAAGTGTGCCTGGATTCAGGACGCTTGTTCTCTTTCATC +GTCTCCATCAGGCCCAACTTCTCATGTCTCAAACGAATTCTTCTTACTGC +TTCTACCTCATCATCACTGTCATTTTCCATACGAACATCTCCATTCATCA +TTATACCGTTTGTGTTTCTTCTGAATCCAAACTCATCGACATCATGAAAC +ACGGACATGCTGATTTCATATTGTCGATCGATGCTGATTGTGAGTGCATA +TCTAGTTTTATTGACAGAGATTCGGGCGTCTGTGAGAGCCAGTTcgttaa +ttttcagatgagttCCTTTCTCGATGGAACGGATCGAAGGCAGGTGTAGG +GAGTGATGGAATCTGAGAAAATATgtttaagaattttttaaatccaaaaa +atgtctGTTAACTCACCGAAAGTTAGAATCCATGTATTCAAAAACAGTCT +GGCTCAGTTCATACAGTAGTTGTTTGCTCGGCATTTGTTCTGAAATGGGA +AAGTTAAAACAAATGAGACACGAAAAAGATGTACTACTCGACGATTTTTT +CCATCTCCATAAATCTGTTATGAATAGCGGCATTTTGAGAGGAAATTcca +agggggactccgaccaaaaatttctaTTGCATTAAACTGTTCGAAAAGTA +gtctattttcccaatatggtagcgaaaaaattccaataacatccgaaatc +cccgaaaaatgccgcacaaagcgaaaaattctcaaaaaaaaagttgttgg +gAAGGACGAAGATCTGAATCCCTAAGGATGATGAATGTCTGGTTAattct +tcttttgaaaatttttgtaatccatggcttttttcttggtttttcttttc +tgaaaatgctttgaacctttcagaaaaacctttagttgaaatgaatgaat +ttttCGTAAAGATGCTTCGCTCTCACATAGTGCAATAAATGATCGTAGTT +TGCTTGAAAAAAGCCTTCAAACCTTGCGTAGCTGATTGCTGAATTACTCA +GAAGGACAACCAGGAAtcttttttaagaaatttgattcatttttaatCGA +GCTGTAGCTCCGCCGCCAACACATACCATATCCCAGnnnnnnnnnnaTCC +GCAAAAATTACCATGTAAGAAAGGCGCTAcgatgccgtggcctaggtttc +tcactgcgcgggaattcaaattctatttttttttcaacgccgtttttcgg +ggttttaggattttttttttgaattttttcgcaataatattcggaaaata +gataactttaaaggtgggtggacatgaaaaaaataatgctctcgaaattc +cgttcaaagatgcccctcgaggagttgaacttgtgaggacgATGATTGAA +AGTGCGGTGCCgcaaccgactgagctacgcgggcaaagagaaagcgcacg +cccgattgcatacataaaggcgaggacgacagctgtacgcagcgtgacat +taagcgttgtacaccgtgacggtagaatgcatactctagctacaaaaaaa +ctacgaaaaatctcctgtccccccacctttaaacactttttaatgcaata +aaaatttttggtctgagtccccctttaattgaAAGAAATAACTTTTGACT +CAACGTATGTCGTTTCCTGTTAGTCTATTAAAATAAGGAAAATTAACACA +CCGAATGTATCGATTGGTTGGACCTCATCTGTGTGTGACCTGTTTGTATA +CCATCTGTCAATGTGTTAGTGCGAGACAGTGGGACCACCAGAGACGAGAT +GTGCAAATATAAGAATGGTCCGTATCAGGCATGAGCCGAATTCCTTATTC +CGTATTctcgattctcaaaatttttattccgctTTTGTCTGGTCCGTATA +GATCACATAGGTTCTgcttaaaatttattttttatcgcttgaaaaaaatt +gggaaacattttttagcgatggggaatggaaaaaaagggggaataaattc +gatttttatactgaaaaacaaaacaagggattggtttttttttaaatcag +ttGTGTTGAATTCAAAtgaagcatttttcaaacaaagaaacaaaaaactt +aaTGAAAGAGCCTGACAACTTTAATCCAacatatctcgttttctgtgaga +gGTAACAAAtacttgtcaactaataagaGTAGTCCGTATAGATCATATTG +GTGCCTGACACAATTTGAGGACTGGGATATGGTATGTGTTGGCGGCGGAG +CTACAGCTCGattaaaaatgaatcaaatttcttaaaaaagaTTCCTGGTT +GTCCTTCTGAGTAATTCAGCAATCAGCTACGCAAGGTTTGAAGGCTTTTT +TCAAGCAAACTACGATCATTTATTGCACTATGTGAGAGCGAAGCATCTTT +ACGaaaaattcattcatttcaactaaaggtttttctgaaaggttcaaagc +attttcagaaaagaaaaaccaagaaaaaaaccatggattacaaaaatttt +caaaaaaaaaattaaccaGACATTCATCATCCTTATCGGCGGAGCACTTC +CATTTTCACAATCCAAATCTCTCGTCGGCTACCAGCATCATGGAGTATTG +AATTGCCATAGGAGACGGATAGAATAGATGATTGAcccattgaaattttg +atggatctgaaaaCATGAGTTGTTGGGGGAAGGATAATTGGAAACGCGCT +CAAAGTACAATGAGAAACTTCATTTACCTACGATCCGACTCGATTACTTG +AGCATTCCTCCTTAGAAATTTTATATATCGAGACGGTTTCtctcttccaa +attttcgaatttcgaatagCCAACTCGTCCCAACTGGCCTTCCATGTTCC +AACCAAAATTCTATTAAACCAGCGACAGTATTCAAAGAAACCCTATTGAT +TAGaactttttggtttgaaaTCTTCATTAGATTCAAAGAGTCCATATCTT +GTCTGATGATTTCCGAGCGAACAATCAAATATTCCGCAGTTGCCAGAGTT +TGGTGATCCAACATTTGATGactcatttcgaaatttagaagcTTCAAGGG +GAAACTTGTACTGTCACATATCAACTTGACACCATCCAAGTTGACGGAAT +TATAGCTTCCCAGTTTTACATTCCGAACAAATGGTTTCTCTCCAGGCTGA +ATCCAGCGAACGTTTCGACTTGATATACTCATCGAATTCACAGTCCAAAT +CATTTTTCGATTACTGAATCAACACTTTTATTCCTTCATAAATTGTTGTA +ATTGTTGAACTTGTGTAAATCCTTATCTCTCCATATCCAGTAATGTATGT +CAATTTTAAAGTGGATTTGCATTCAGGTGGCTCCTTCTCTTTCACAGTCT +CCATCAGTCTTTCATATGCTCTCGTTGACCTGCTATTTTCGTTTTCCATA +CAAACATCTCCATTCATCATTATACAGTTTGTGTTTGCTGGAAATCcaaa +ttcattttcatcatGAATCTTGTTGATTCTGAACGGGCGATCTTCAATTG +CATATTTTcgatcaattttgagctcatatttCGTTTTGTTCTCGATGAAC +AATTGATTGTCTTCAAAAACTAGTTGGTTGATATTTAGACGAGCTTCTTT +TTCGACTGAACGGAGAGCAGGCAGGTGTAAGGAGAGatggaatctggaaa +aatactTATTGAAAAGTTATCTGGAAAGTCCAGAAggcgtaaaacctgta +atagtagtacatctcggttcctgtcaaagatatcaaaaatttgtaaactg +ataaactgttccTGATTTCATGATAAACGATGGAGCTaaaaaaaaTAAGC +TCGCACTTTACGGACCTgcttttacaggttttacggtattttcagattta +gttttattttttaattctaaggACACcagaaacatctgaaaacaaCCAAC +TGAATAGCAATTTTGCCGTTTCCGAATTCATACTCACCGAAAACTAGGGT +TTTATGTACTTCAACAATTATTTAAAGGCACATTCTCCTAcagcaaaatt +caaatttaaaagttccaAGGTTTTCGGAAATAGTTGGTGATTCATTTTcg +aattaaaggtgggggacatgaaaaaaataatgttctcgaaatttcgttca +aagatgcccctcgaggagttgaacttgtgagggcgatgatttaGGGTGCG +Gcaccgctaccgactgagccacgcgggcaaagagaaagcggacgcccgat +tgcatacataaaggcgaggacgacagctgtacgcagagtgacattaagcg +ttgtacaccgtgacggtagaatgcatactctagctacaaaaaaactacga +aaaatctcctgtccccccacctttaaactcACCGAAAACTAGGGTCCATG +TATTCGAAGACATTCCGGCTCAACTCCTTTTGATGTTCTGAGAgcatttt +ttatctgaaataGAGATAATAGGACAGATGGGATATGGGAACACGAGCAA +TAAAACTAATACTAAGTGTAAGCCAGGCGCATTTTCCCTGCGTCtcaact +tatttttttctgacagCACGGTGTTCCGATCGGCGAAACCGGTTTAGTAC +ACGTGGCATCGCAGTGGAGCGCAGAAGCCCAAgcgaaaattcagtttttt +gttagtttttcaggtttaaTGAAGGGCCCGGCCCCGGATaggatttttac +aataaacaAGTTTTGCAGCaattgaaataccgtaaaatctgtatttgaAG +Ggccccctttaatagaagggccctccaagaggggtttggaaaaatagaag +ggccggcccttcttaatacaggttttacagtatgtttttttaaaaaaaat +gtttgaacacATAGAAAAATTATAACAGACGAACGAACGAGAGGGAAAAG +TatacaaaagaaaaatgaaaagatccCAAAGGAGGAACAAACTGAAACAA +CCATTCTGTTCGCCGCGAGTCTCTCTTTTATATGTTTCAGAAATGTGTGG +GAACCGTATGCGGGAGAGTTGTATATGAGAAAAGCGAATAAAATATCAAA +GGTGACAATTTAGAATATTAcaagaattgaaaagaaaGTCGTTCTTTTAT +AAAACAAGATGTTGAGGTTAATAAATGGACAAATGTGCAATGAACAATAA +ACTTTTATATCTTTCTCTTTCGCGTTCTTCTGTATCGAAATGATGTTCGA +CCACATCTACTGTGACAGTCAAAACGCATTTCcgaagaatttttcagatt +ttgagattttctggaaggttctcggaacatttttgatttctggagTTTAT +CCAATACTAATTTTTCTAACGCaaagatttattgaaaaaaaaaacatgac +tTTCAGCAAAGTTATTGGTCAGTTACAATGCAAAGGtaatttttcaagca +aaacgttttcaaaaagaaaaaaaaacaatgaaaaagaCAAATTAGAGAAC +ATATATCCAGAAACTCAACATCGTTATCGTTGGAGCACTTCCATTTTCAC +TGTCCAGATCATCTCTTGTCTGTTAATAGCACCATGGAGTATCGGATCAT +CATAGGAGACGGATAGTATGGAGGATGGACTCATTGGCATTTtgatgaat +ctgaaaatatcgttTTTAGAGAACAGGTAATTGCAAACACGCTCTAATCA +CAATGAGAAACTTCACTTACCTACGATCTGACTCTATCGCTTGAGCAATC +TCTCTTAGAGTAGATATGTATTCAGATAGTTCTGATCCTTTAACTCGAAA +AGACCAATTCGTCCCAACTGGCCTTCCATGTTCCAGCCAAAGATCCATTA +AATGAGCAAAAGTGTTTAGAGAAATCGGAGGGAGTCGAACTTTTAAGTTT +GAAATCTTCATGAGTAGATCCATGGAGTCATAATTATAAAGTTGCGAGCC +GACAACGAGATACTCCGCGTTTACAAGAATTTCGTGACCCAAGATTATAT +CGCTCGCTTCGAAACATAGCCAATTTAAGGGAAAACTTGTTTCGTGACAT +ATCGATCGAAGACCATCCAAATTGGCAAAACGATAGCAGCCaagcttcat +ttttcgaacaaaCGGCTTCACTCCAGACACAATCCAACGAAGGTTCTTAG +TTGATATAATCATGAAATCCACATCCCAAATAACAGTTCGATTCCCGAAC +ATCGTGGCTATTAGCATTTTCATTCCCtcataaatttttgtaatttttga +gcaTGTATAAATCCATGGCTCGCCATTTCCAGAGGTGATTGTCAATTTTA +AGGTAGACTTGGATTTAGGTATCCCCTTCTTTTCCAACGTCTTCATCGGA +ACCGATTCCTCATCTCTCAAACTCATTCTTCTTAATGTATTTACATCGTA +ATTACCGTGATTTTCCATACGAACATCTCCATTCATTATTATATCCTTTG +TAAATGTTTTAAATCCGAATTCATCCACATCATGATCTACGGGACCATTT +CTTCTCAACGGAGGTTTCTcgatttcatattttcgatCGATGCTGAGTTT +ATATGTAGTCTTGTTGACGGTGATTTCGTTATCATTCAAAATCagtttgt +tgattttcagatgagcTCTTTTTTCGACAGAACGGAGAGAAGGCAGGTGT +AGGGAGAGgtggaatctggaaaaaattaaataatttctattcagattttc +aagagattttcggaaatctGAGAACCCCAGAAACTTATAAGTTCCAAGGT +TTTCGGAAATAGTTGGTGACTCATTTTCGAATTgatttatctcgctttct +ctaaaagatataaaaaacttgaaaacaagtaaaatattggtgataatatg +ataaacattcttgcagttgacaattttttgatatctctcacaggagccga +gataattaaactcaaaATGCAAGCGTTTTTAGAGTGTAAATGCTGTGTTG +GAACACTACTTCtatgagcccaattatctcggttactgtaagagatatca +aacagctgtcaattgacaaaatattggtgataatataaccaacattttat +cagttagcccATTGTCAACATCTCTttcaagaaccgagataaatttggtc +aaaaatcggaaaatttctaacatttgagtgaaatttaaagattttatGTA +CTTCAACAATTATTTAAAGGCACATTCTCCTAtagcaaaattcaaattta +aaagttccaatcaaaaagttgttaattagtaaaatattggtgataatatg +ataagcatttttgtagttaataactttttgatatctcttacagtaaccga +gataaccAAGCTCAACGTACTTGCTCTTTCTAGAGTGTAAGTCACCGTAA +ATGCTTTAACGGAACACCACTTttatgagctcaattaactcggtttctgt +aagagatatcaaaaagctgtcaactgacaaaatattggtgataatataac +aaaaattttatcagttggctatttttttgatatctcttccaagaaccgag +ataaatttggtcaaaaatcgagaaattgcTAACATTTgagtgaaaattga +agattttatGTACTTCAACAATTATTTGAAGGCACATTCTCCTaaagcaa +aattcaaatttaaaagttccaAGGTTTTCGGAAATAGTTGGTGATTCATT +TTCGAATTAAACTCACCGAAAACTAGGGTCCATGTATTCGAAGACAGTCT +CCCTCAATTCCTTTAGTAGTAGTGGTTGTGACATTtatctgaaatgaaaa +taataaaatatgaTGAGAcatagaagaagagaaactaAGAATCGGAAGCT +CAACATTCACGAAAACTACTCAAAAGTGAAACAGTTAAAACTTGACAGAA +CTCACATCGATCACAGAATCTTCAGTTAAAAAATGGCGAAACCCATGAAA +TTGACATTGAGCCAATTGATCGgtgttcctgtgaaaggtatcaagaACTT +GTCATTTGGTCAAATGTTTTTGCTatcatgatgaacaatttatcagttga +gcacttttcGACACCTTTCACAAgtgccgagataaattggctcaaagtcc +TGGGTCCCAACAgatttcccagttttttctccttctttgtCCCTAGCCAA +AAGGTGATGACTGataagaaataattttttatcatcaGCCGTTTTTGTTT +CTCTGATGGACATTGTTATACGTGTCACCTTGTGATGCTCATGAAGGTGT +CAATTTAGAGAGCCTTGCAAAACTtgtgactgaaaatgaaactgGATGAG +CACcttcattttctgattttcttttctctagTGACTTCAACCTTtaatat +ctcggctcctgtgagagatatcaaaacattgtcaactgataaaatgttaa +tcacaatatcagaaatattttatcagttgacaaattgttgatatctctca +taggaactgagataattcagATCAAAGTGCAAGAATATCCTTAAATGTGC +AAGGCTCGCCTACAAGAAGAAATACAGTATCTTtgaccctaattatctcg +cttcttgAAAGAGtgacaaaaaagttatcaactaataaaatgtgagTTAT +AAAAATGcgcacattttattagttgattactttttgatatttttgctaga +aacagaaaacaataGAATTGAAGGAAGAGTTAGTTAGAGGGTTCCTACAC +CCTGTTaaatttaagccaatttttctcattttctgtaaaagatatcaaaa +agttgtaaattagtaaaatattggtgataatatgataaacatttttgtag +ttgacaactttttgatatctcttacagtaaccgagataaccAAGCTCAAC +GTACTTGCGCTTTCTAGAGTGTAAGTCACCGTAAATGCTTTAACGGAACA +CCACTTTTACGAGCTCAATTAAgtcggtttctgtaagagatatcaaaaat +cttaaaaaaaaatcaaaaatcggaaaatttctaacatttgagtgaaaatt +aaaagattttataaacttcaaaaaataattaaaggCATATTCTCCTACag +caaaattcttaaaattccatgcgcctttaaagttccttaaaagccaattt +ttccatttttttgcagcttcattaaaaaaaaagatttttatagAATCTac +gaatcgagaaaaatgggcTTCAAGaaactttaaaggctcatGGAACAGGA +GGAGAAAAACAATATTAAAACTTCAATGAATATCTCTCTCGCCTAAACAT +TCAATTCGAAATTCCCGCGCTTTTCTGTCCCCGTCTATCCATCCCTCCCC +acgaaaaatgtgtcaatatagagggaagagacgcagacacagtGCCTAGT +GTCTAACATAAATGATCGATAGAGAAAAGGCTATGTACGCGTTCTCATCG +CTTTCGAATCGCGACACTCTTTCCCTCTCACGCCTGCGTCCCTCACTCCG +CCACACTCTCTCTCCCTTTCTCTACTATAGAAAAGGAAGACGTGCCCGGC +CCGTCGTTTGCATCGCGGAGCCTTTAGCTCCACGGGGtcttctccttccg +ttcttttcctcctctctattccctacactctctcgctctctcactctctc +tctcttttcaattctttcccatcgtcatcatcaatttttcgttcGCTACT +CCATTTTTGGCGGATGAAAATGAGCCCATTTATTTTAAATTGCTCCGAGA +GCCTGAACTGCATCGTTTTCATTTAATTACGGTTGTGATGTTTGATTGGC +CCGAGATGGCTTAATTTTTGCGcgggagatttgaaaaaagaaaacgttcT +AATATGTAGGGTTTTTAGTGtctaatgtttcaaaatattggttgaatttt +tgaatttttaaaataatttctaaattctcaaatctctgtgaaataatatt +ttagaaaattgaaatttcggcaatttttaaaaacataattcaaaataaaa +actttgagaaaatttggaatctcGAGGTTCTGAACTTCTTGAAACCTtaa +attcttggattcttagttttttgaatgtttggatttttaaaattctgaaa +ttcccagtttctcaaattcttagacttgaagattctgagactctaggatt +ctaaaattttgaaattctgaaatctttagattaggaatttttcgaatttt +gcggGTTTTGGATActtggattttgagattctgacactttcgaattccga +aattctgaagtcctgGGAATCggaaattatgagattctgaactcCCTGAA +GCCAATTTTCATTAGCTTTGTCCTGTTTAGCTTaaaaacagatttcaaaa +atagatttttatcaaaaattcttaatttagaaaaccacaaaaatggaACC +AGATTTTCTACGAATTAagccctctctctctctctctctctctctctctc +tctctctctctttccaaTTAAACTATTTAGAAAAGGTCCTCTTTTGATCC +TAGAAGACATCTCACGTCATctcatctctctctctctctcatctGTTATG +TATTGGAtaagcgagagagagagagagagagagagagagagagagaggaa +ggtCAAATCGATAAGagaagataagaaaaaaggaggcAGGAAGATTTATG +TATGCATAATAGGACCTTTTCGTTATCAGCATTTTTATATTATTACTTAA +TTAGTGTAATTAAGCTAGCATTATCTATAGAGAAAACGTATACTAATTTC +TTcatgtggcctagttttccgtcagctggcctaactttgaaatttctcgg +TCATCCAAACAAATTCGTTAAAATCCGTTTCAGCTAAATAATTCCTTATC +TCTTTTTAATCTTCCCTCAACATGACTCATCttgttttcccttttttaaa +gcattttcccatttttagtattacttcttttttctgtttcgtcTGAATCA +TCGGAAAAAATTTACTGGCAAAAAATCCCtaaatttttatcactttattc +tttaagcttaattatcttgattccccTAAGAGATATCGAGCatctgtcaa +cagataaaatataggaaatattatcacaaactttttatcagttgactgaa +ttttgatatctctcataagaactgtgataactgagctcaaggTGGAAGCG +TTTTTAAGTTACCTTAATTGCTCATATCGTTTGTGCTTtaagcctaatta +tctcggttcctgtaatagatatcaaaaagttgtcaactgataaaatgttc +aggaaccgagatatctGGGATTCAAGAAGCGAGTACTAattaaaagttcc +aaaattcagaaaaatctaaacATCAAAACTCCCTTAAATCCATTTTGCTA +GTGTGTGTCCTCCTGAATAAATGATATCCTTTCCCTGCCCCTTTCTGTGA +GGGGGGTCggtttcattttctttcataTTCTTCCCCTTTTGCTTACCCTT +ATTCACAATCTCCATCTCTCCTATTCCTATTTCTTGATGTTCTTGTTTTA +TATATTCCGTTTCCCATTGAATGctcctctctccctctctctcttttcgt +TTTCTACGTCCCTTCTCTTACTCTTGATACTGACACCAACTAGTAGAAGA +CTTCTGATTCAtggacacacacacataccCAAAGACATTCGGGTGTTCCC +ACGGGAACACCCGGGACCGAATACTTTTGGCTTCTGGAGGGTCTTGACTT +ATTTTTTCCCTCGTTTTGttcttttaaaggcgcatagtattcttagattc +ttatattcttagattcttagattcttagattcttagattcttagattctt +agattcttagattcttaaattcttagattcttagattcttagattcttag +attcttagattcttagattcttagattcttagattcttagattcttagat +tcttagattcttagattcttagattcttagatccttagattcttagattc +ttagattcttagattcttagattcttagattcttagattcttagattctt +agattcttagattcttagattcttagattcttagattcttagattcttag +attcttagattcttagattcttagattcttagattcttagattcttagat +tcttagattcttagattcttagattctttttcttgtctcattattaCACA +AGAAATATTTAGTGCTGAGCAATCATCTTCTTAATTTCCCTCCCCCTGAA +CTACACGAAAATCCATTCATCACTTTGCGCTACTCAACAGCACCACACAT +TTCTTATTACAcaattaaaattgttttctctgtttctctaattctctcac +tctctctctatctttctTATTAGCTTCATATATCCGCTTTTCGTTATCCT +AGGCTCATGATGCCGCCGGCCGACTAGATTTGGTTACCTAGGCCGCTTGG +TTTTTTGgctataactttgttcaaaactGGTCTACGAAGATGGTTAATAT +ATCTATCGAtaggaaatcaaattttacacCGATTCAATAGAAGGTATATA +GATTTGAATGATTTCTAATTGAGTTATGTTCCATTATCCTAAAATCCTTT +CTAGACGCTTCTAGAGCCTAGAAGCACAAGTTTTGTGCCGTCTTTTTAAT +TTTGGCCTGTCtagacaattaaaaaaaacttcaaataactCATAgtcagt +tttcttttcttttcccaaTTCCCAgaacaaatcaatttttgccCCTAAGC +GAAACGCTAGGCAAACATGATTTATGGTAGTTTGTCTCTACTTTCTACCT +GTCAACCAATCTCACTTCCCTCTCTAGGTTTTACCCTTTTACGTTTCTTT +TTGAGATCTAAAAGCAACCTTATATGTTCCcacctagaaaaattcaatcc +aatttttaaatgaaaaagctaaaaaaaatgCGGTCGGCGGCACTGTTATC +ATTGTCCTCTGTAGCGAAGAAGAGTGTGCGGCAGCGTGACCGAGGGGTTA +ACTCTCCTGTTTTTGGATCTGTCACTGTCAAGTTCGATTCCACCGAGCGC +CGAACtctttccttccttttttgaattatttcttGAAGTAGTGTATTGAT +TCTAaagtcatttttaagcttGGAAAATTCCATTCCTTCTGTTTTTGTCT +CTAAAATCtcatgaattttagaaatttctatatttcccTCCCAGGCTGGG +AGTCCCATCCCGAAATTTCGCCCCCTCTGAAAGCATATACTATTGacatt +tttgcaaaaacgACGGGAAATATATAGATGAGGGGGTCCAAAAACGCATA +AAAATCTTAATATTGGCCTGAGTACGCCCATTTACGAGCAGCCTTCTCTC +AAGATATGGGTGGGGTAggcatttccattttttttgggacctcctTTCCC +TTTATTATATATGCCTCTACCCCCCgaaaatatatgaatatttagaaaat +tgcagaaaatattttttgaattttgaaatttttaagttttttcaaaagtt +tattttcaTTAGCGCGCCctttcagtttcaaaaccCCTTCCCTCCTGTAC +GCCTTTCATTCCCTTCTCTCTATGCGACCACGTGGCCTAGTGGCTAACAC +TGggacacaggtgattcgcgaacaatccgttacggattcTCCGCCATTCG +CGCGCGGATGAAATAGGAATCGTATACGGACCGTACGCGaatccgtaacg +gatccgtttgcaACTTATTTCTTGAAAACCCTCGCCgttccttttttcag +tttctattattttttgctgAGTTTTCATGATAGTTGTAGACTTAGTATTC +GGAACTTTATTAAGAAAACAtgtaaaagaaagaaaaaacatcagAAGTAC +AACATtaagttcgaaaatttatcaaaatccTGCTTTTTTGGGTTGTTGAA +CGATCATCCAAAACGAAAAGAGAcctgcaaaaaatttgggaatctgTCAG +AACATGTTGCATACTGATCACCTATTACTatccttttttgcttttgggtt +ccaatgtttttctcgtttttaacGTTGGAGTCGGCTTGCTCTATAGATGT +CCATTGCTGAAAAGTGTAAAAgtcattgtttcgaaaattagcGTATTTTA +TACTTACATTCGTCAAGCATCTTTCCTGGAGCAAACGCGAGCTTCGAATC +AAtcattttcggtcattttgctCACGAAAAGGTTAAGTGATACCTATAAC +AAACCCTATGTTTCGAAGAATTACCTTTGTGTTACAAACCTTTTTTCCTT +GTAGAAtcgtctttcgaaaaaaatcattgtcaaaaatcaacatatttgcc +aggaaaagtgagagaaaacggcaaaaaataggtttaaaatgcaaataaat +gatgcaaaaatATGATGGAAGAGGTAAGAGAAAGCTAGTCCCTCACAACT +CGGCCATCcggaacggatccgttcgcgaatgGGCATGGGAGCTATCTCTC +GACCTCCAGCTGCATCCGTATCcggtccgttcgcgaactccgtatcctgt +ccgattgcgaatgttgaaaaaacggatccgttcgcgaactcagaTTCGCG +AAACTGcccgtaacggacccgttaCGGATAGAAAACCTAGTGGACAccga +aacggatccgttcgcattttacctgtggaGTTTTTGATCCGACCCTCACG +AGTTCGACTCCTTGTTGCtcaaaatcttcttttttccttttttgattctt +tatCCCCAAAAGGGCGCATTTGGTCCCTTCCCTAATTTATAGCCTTGcac +tttttgggattttaattgaatttttctggagAGAACTCATCTAGTGAAAG +TGCTCGCGCTGATGAAGTAATCAGTGAAATGCGATAGGAAAACAGGGGCT +TCTCAAAAAACGTTCTTGTGTAGGTTTACGAGCCGCTCGTAAATCTACTA +GAGATTTTGTAAAGGTAAAGGGAATCATTCTGAGGAACAAGATATACCTT +ATGAGGTCCACCGTATACatgaagtttgagctcaattatctcggttcttt +tgaaagatatcataaagtaactaactgataaaatgtttatcagtttatca +ccaatattttatcagttggtcacttttttatatcttttactggagccgag +ataattgagttcaaagtgaaCTCAGCAGAACAATgggttctctgcgtctc +tcactgaTCCATCTCTCTACTCGAAATCCTACTAGTTTTGTATTATAATG +TGTCCAGTCGTCCGTTTCAAATCCATTCCGCTGACACCCATTTGTTTCCC +TTTTGGTCACACATTTTGTCCTTTTTCGGATAGACAGACATACAGACAGA +CatagaactttccagaaaacaCCACAATTAGCATAGCTAAGGGACCATGG +TTTTCCCCTTTTATGTAGATTCTCACACATTTCCTAGTCTTAATAATAAT +AAGCTCAGTCTCTCGCCTAGGagcttcctctctctctctctctctctctc +tctctctctctctctctctctctctctctctctctcactttctCCCTGGA +GAAAAGAGAgcttattattattttttcgtcgcttcttccatcatttattt +tcttattttcatttacgcttattactcctctcattttatttttactggag +aaatttatGTGAAAGGAtctagaacttgaaaaaaactgaaaaatcgttAG +TGGCACTTAAGGGACAAATGGGACAGtctcattatttttaaatgttatAG +TCTattttgtcttgaaatttccaacattctGAGCCCCATATCGACTACAT +TCTGgcagttttgattttcgaccataATTAGGCCGCGGCCCGGCCGGCTG +gcccaaaatcaaattttaaggaTTATAGCCAATATTatactcaaaatttc +acaaatttcataagaaaaaatataacgATATTTGTTTTCTCTGAACTAgg +ccacttttcaaaatcacagaattttagaattctaaaaattcggatttttt +gatttttgattttttttttctccaaaaagattaatatttttcttctctct +tgtctaacacaaaaagtgaaaaaatttcttcgaATGATATTGTTTTTTCT +GCCTGGGATTAGTGTCTTTACTTCTTTTTCCCCTGCCGTTTGACAAGAAG +AAACATGACAAATGAATTGGCattcagaagaagacgtgCGACAAGAAGAT +TCTAGTAGTAGAAGCATAAGAATTTGTTTCATTTGTAGAGTTTTGAGAAG +ACTAGGCTCTTGGTAAACTTCTCAAGCGCGCCCTATTGACAAAAGACACT +TAGGGGACACATGGGACAGTCTAAAGATTTTTGAGAGCtacattctattt +tttcataaaatttccaacatgtTGAGCCCCATATCGACTATATTCcaatc +aatttgaattttcagaaaattttggtgcaaatgcgctccaatgcgaaaag +tgaaaatttttgaaacccagccatgattatacttattttgtcAGCCTTAA +TTAGCTAAATTCAAATCTTCTAATTTTATTGCTCTAGGGGCAAAATAAAT +CGAGTTATGACAGTTTTAGTGGTGCTTaatttttgctaaaaaccGTCGCT +GACACTTAGGGGACAAATGGGACAGCGTAAAATTGTTCGAGAACTATAAT +CCAATTTGACCttaaatttccaacattttgagccccatattgaaTATATT +CCggatatttttaattttcaggtgcAAATGCGCCCTAatgataaaaaaat +caaactttaaGGAATATAATACTAAAATATaatactcaaaatttcagaaa +ttttgtgagaaaaacAAATCTGTTGTTTGCTTTTTCAGATAACTCGCTCT +ATTgcactttttttctcaatttccgttTTAATCTAACTAACGTTTCCCTG +CCTTATTCATTCGACACACATCAAGTTGGATGGAGCAAGTAAATTAATTC +TCTCCCTCCCTTCGCTTTCCCACGTTTCCCTATTtctctaagtctcgctt +ctctttctatactctctcgatgtctctgcgtctctcctccctctttctct +ctctctcttcctaaTTAATTCGACACGAGACACGAAGCACCCAATAATCC +ATGTCCTTTTTCCGTCCCGTTTCTATTGGTCCCCTCCCCATTTTCATCAT +TGAACAggcagaattttcaggatgtCATCTGAAGCGGCTCCAGAAGTCGT +CTCGGCCACGGCCTCCACAACGCCGGCGGCCACGCCCCCTTtgaaagggg +gcggagttCCGGGTGGTGGTGGGACAACTACCGCCGAGCAACAACAAGTC +CCATTTCGTAtgtttcatttctttctttttttaaaacaaaattttcaata +gtttatcgATAAAATGGACGGTTTCACTTCAAGCGCGCTCcaattgcaaa +ttttgagaaaaatgaaaatttttgaaacctagtcatgattatactcattt +tatcTGTCTTATTTTGCAGATTCCGAAACTAAAACTTTCATTGTTCCAAG +TGCAAAATTAACCGAGTTATTGtaattttaatgaatttaGTCAAATGCGC +CACATTGctaaaaattaacatttttggaactaaaccatgtttatactcat +tttatcTGACTTGTTTTGCTGATGACACAACTGTTTTCATTGCTCTAGCT +GCAAAATGAACCGAGTTATAACAGTTTTAATAAATATGACCAAGTGCGCC +CCATTGAGAAAAACTAGAATACCAGAACCCAGTCTTGATTATACTCTTTT +TATCTGGCTTGTTTTGATTATTCCAAAACTAACAAGTAAAATTTTCTAGG +TGTAAAATGAACCGAGTTATGGCAGTTTTAAGAAACTTGACAAtatgcgc +tccattgacaaCAGACACTTAGGGGACAAATGGGACAATTTCTGATAACA +TATTCAACTTTGTcatgaaatttccggaaatttgaGCTCCATATCGACCT +TATTCcgattattttgattttcgatcaAATTTACCAGTAGGCCGCGGCCT +CGGCTGcggtcgaaattcaaatttcaaggaaTATAGGCAATATTatactc +aaaatttcacaaattttatgGAGAATCCGAATCTAGCACTTATTTTTGAT +AGATATGCgtctatagaaaaaaaaattgcggggttttccaaaaatccgca +aaaaaatttcgtgaCTGTAAACAAGAGATACATATTTTCAGGAGGCTTCT +CACTGGAATATTAAAAATTCCTCGTTTTTGGTCTGTaaaaannnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnTCTCTC +TCTTTCCAATTAAACTATTTAGAAAAGGTCCTCTTTTGATCCTAGAAGAC +ATCTCACGTCATctcatctctctctctctctcatctGTTATGTATTGGAt +aagcgagagagagagagagagagagagagagagagagagagaaggtcAAA +TCGATAAGagaagataagaaaaaaggaggcAGGAAGATTTATGTATGCAT +AATAGGACCTTTTCGTTATCAGCATTTTTATATTATTACTTAATTAGTGT +AATTAAGCTAGCATTATCTATAGAGAAAACGTATACTAATTTCTTcatgt +ggcctagttttccgtcagctggcctaactttgaaatttctcggTCATCCA +AACAAATTCGTTAAAATCCGTTTCAGCTAAATAATTCCTTATCTCTTTTT +AATCTTCCCTCAACATGACTCATCttgttttcccttttttaaagcatttt +cccatttttagtattacttcttttttctgtttcgtcTGAATCATCGGAAA +AAATTTACTGGCAAAAAATCCCtaaatttttatcactttattctttaagc +ttaattatcttgattccccTAAGAGATATCGAGCatctgtcaacagataa +aatataggaaatattatcacaaactttttatcagttgactgaattttgat +atctctcataagaactgtgataactgagctcaaggTGGAAGCGTTTTTAA +GTTACCTTAATTGCTCATATCGTTTGTGCTTtaagcctaattatctcggt +tcctgtaatagatatcaaaaagttgtcaactgataaaatgttcaggaacc +gagatatctGGGATTCAAGAAGCGAGTACTAattaaaagttccaaaattc +agaaaaatctaaacATCAAAACTCCCTTAAATCCATTTTGCTAGTGTGTG +TCCTCCTGAATAAATGATATCCTTTCCCTGCCCCTTTCTGTGAGGGGGGT +CggtttcattttctttcataTTCTTCCCCTTTTGCTTACCCTTATTCACA +ATCTCCATCTCTCCTATTCCTATTTCTTGATGTTTTGTTTTATATATTCC +GTTTCCGATTGAATGctcctctctccctctctctcttttcgtTTTCTACG +TCCCTTCTCTTACTCTTGATACTGACACCAACTAGTAGAAGACTTCTGAT +TCAtggacacacacacataccCAAAGACATTCGGGTGTTCCCACGGGAAC +ACCCGGGACCGAATACTTTTGGCTTCTGGAGGGTCTTGACTTATTTTTTC +CCTCGTTTTGttcttttaaaggcgcatagtattcttagattcttagattc +ttagattcttagattcttagattcttagattcttagattcttagattctt +agattcttagattcttagattcttagattcttagattcttagattcttag +attcttagattcttagattcttagattcttagattcttagattcttagat +tcttagattcttagattcttagattcttagattcttagattcttagattc +ttagattcttagattcgtagattcttagattcttagattcttagattctt +agattcttagattcttagattcttagattctttttcttgtctcattatta +CACAAGAAGTATTTGGTGCTGAGCAATCATCTTCTTAATTTCCCTCCCCC +TGAACTACACGAAAATCCATTCATCACTTTGCGCTACTCAACAGCACCAC +ACATTTCTTATTACAcaattaaaattgttttctctgtttctctaattctc +tcactctctctctatctttctTATTAGCTTCATATATCCGCTTTTCGTTA +TCCTAGGCTCATGATGCCGCCGGCCGACTAGATTTGGTTACCTAGGCCGC +TTGGTTTTTTGgctataactttgttcaaaactGGTCTACGAAGATGGTTA +ATATATCTATCGAtaggaaatcaaattttacacCGATTCAATAGAAGGTA +TATAGATTTGAATGATTTCTAATTGAGTTATGTTCCATTATCCTAAAATC +CTTTCTAGACGCTTCTAGAGCCTAGAAGCACAAGTTTTGTGCCGTCTTTT +TAATTTTGGCCTGTCtagacaattaaaaaaaacttcaaataactCATAgt +cagttttcttttcttttcccaaTTCCCAgaacaaatcaatttttgccCCT +AAGCGAAACGCTAGGCAAACATGATTTATGGTAGTTTGTCTCTACTTTCT +ACCTGTCAACCAATCTCACTTCCCTCTCTAGGTTTTACCCTTTTACGTTT +CTTTTTGAGATCTAAAAGCAACCTTATATGTTCCcacctagaaaaattca +atccaatttttaaatgaaaaagctaaaaaaaatgCGGTCGGCGGCACTGT +TATCATTGTCCTCTGTAGCGAAGAAGAGTGTGCGGCAGCGTGACCGAGGG +GTTAACTCTCCTGTTTTTGGATCTGTCACTGTCAAGTTCGATTCCACCGA +GCGCCGAACtctttccttccttttttgaattatttcttGAAGTAGTGTAT +TGATTCTAaagtcatttttaagcttGGAAAATTCCATTCCTTCTGTTTTT +GTCTCTAAAATCtcatgaattttagaaatttctatatttcccTCCCAGGC +TGGGAGTCCCATCCCGAAATTTCGCCCCCTCTGAAAGCATATACTATTGa +catttttgcaaaaacgACGGGAAATATATAGATGAGGGGGTCCAAAAACG +CATAAAAATCTTAATATTGGCCTGAGTACGCCCATTTACGAGCAGCCTTC +TCTCAAGATATGGGTGGGGTAggcatttccattttttttgggacctcctT +TCCCTTTATTATATATGCCTCTACCCCCCgaaaatatatgaatatttaga +aaattgcagaaaatattttttgaattttgaaatttttaagttttttcaaa +agtttattttcaTTAGCGCGCCctttcagtttcaaaaccCCTTCCCTCCT +GTACGCCTTTCATTCCCTTCTCTCTATGCGACCACGTGGCCTAGTGGCTA +ACACTGggacacaggtgattcgcgaacaatccgttacggattcTCCGCCA +TTCGCGCGCGGATGAAATAGGAATCGTATACGGACCGTACGCGaatccgt +aacggatccgtttgcaACTTATTTCTTGAAAACCCTCGCCgttccttttt +tcagtttctattattttttgctgAGTTTTCATGATAGTTGTAGACTTAGT +ATTCGGAACTTTATTAAGAAAACAtgtaaaagaaagaaaaaacatcagAA +GTACAACATtaagttcgaaaatttatcaaaatccTGCTTTTTTGGGTTGT +TGAACGATCATCCAAAACGAAAAGAGAcctgcaaaaaatttgggaatctg +TCAGAACATGTTGCATACTGATCACCTATTACTatccttttttgcttttg +ggttccaatgtttttctcgtttttaacGTTGGAGTCGGCTTGCTCTATAG +ATGTCCATTGCTGAAAAGTGTAAAAgtcattgtttcgaaaattagcGTAT +TTTATACTTACATTCGTCAAGCATCTTTCCTGGAGCAAACGCGAGCTTCG +AATCAAtcattttcggtcattttgctCACGAAAAGGTTAAGTGATACCTA +TAACAAACCCTATGTTTCGAAGAATTACCTTTGTGTTACAAACCTTTTTT +CCTTGTAGAAtcgtctttcgaaaaaaatcattgtcaaaaatcaacatatt +tgccaggaaaagtgagagaaaacggcaaaaaataggtttaaaatgcaaat +aaatgatgcaaaaatATGATGGAAGAGGTAAGAGAAAGCTAGTCCCTCAC +AACTCGGCCATCcggaacggatccgttcgcgaatgGGCATGGGAGCTATC +TCTCGACCTCCAGCTGCATCCGTATCcggtccgttcgcgaactccgtatc +ctgtccgattgcgaatgttgaaaaaacggatccgttcgcgaactcagaTT +CGCGAAACTGcccgtaacggacccgttaCGGATAGAAAACCTAGTGGACA +ccgaaacggatccgttcgcattttacctgtggaGTTTTTGATCCGACCCT +CACGAGTTCGACTCCTTGTTGCtcaaaatcttcttttttccttttttgat +tctttatCCCCAAAAGGGCGCATTTGGTCCCTTCCCTAATTTATAGCCTT +GcactttttgggattttaattgaatttttctggagAGAACTCATCTAGTG +AAAGTGCTCGCGCTGATGAAGTAATCAGTGAAATGCGATAGGAAAACAGG +GGCTTCTCAAAAAACGTTCTTGTGTAGGTTTACGAGCCGCTCGTAAATCT +ACTAGAGATTTTGTAAAGGTAAAGGGAATCATTCTGAGGAACAAGATATA +CCTTATGAGGTCCACCGTATACatgaagtttgagctcaattatctcggtt +cttttgaaagatatcataaagtaactaactgataaaatgtttatcagttt +atcaccaatattttatcagttggtcacttttttatatcttttactggagc +cgagataattgagttcaaagtgaaCTCAGCAGAACAATgggttctctgcg +tctctcactgaTCCATCTCTCTACTCGAAATCCTACTAGTTTTGTATTAT +AATGTGTCCAGTCGTCCGTTTCAAATCCATTCCGCTGACACCCATTTGTT +TCCCTTTTGGTCACACATTTTGTCCTTTTTCGGATAGACAGACATACAGA +CAGACatagaactttccagaaaacaCCACAATTAGCATAGCTAAGGGACC +ATGGTTTTCCCCTTTTATGTAGATTCTCACACATTTCCTAGTCTTAATAA +TAATAAGCTCAGTCTCTCGCCTAGGagcttcctctctctctctctctctc +tctctctctctctctctctctctctctctctctctctctcactttctCCC +TGGAGAAAAGAGAgcttattattattttttcgtcgcttcttccatcattt +attttcttattttcatttacgcttattactcctctcattttatttttact +ggagaaatttatGTGAAAGGAtctagaacttgaaaaaaactgaaaaatcg +ttAGTGGCACTTAAGGGACAAATGGGACAGtctcattatttttaaatgtt +atAGTCTattttgtcttgaaatttccaacattctGAGCCCCATATCGACT +ACATTCTGgcagttttgattttcgaccataATTAGGCCGCGGCCCGGCCG +GCTGgcccaaaatcaaattttaaggaTTATAGCCAATATTatactcaaaa +tttcacaaatttcataagaaaaaatataacgATATTTGTTTTCTCTGAAC +TAggccacttttcaaaatcacagaattttagaattctaaaaattcggatt +ttttgatttttgattttttttttctccaaaaagattaatatttttcttct +ctcttgtctaacacaaaaagtgaaaaaatttcttcgaATGATATTGTTTT +TTCTGCCTGGGATTAGTGTCTTTACTTCTTTTTCCCCTGCCGTTTGACAA +GAAGAAACATGACAAATGAATTGGCattcagaagaagacgtgCGACAAGA +AGATTCTAGTAGTAGAAGCATAAGAATTTGTTTCATTTGTAGAGTTTTGA +GAAGACTAGGCTCTTGGTAAACTTCTCAAGCGCGCCCTATTGACAAAAGA +CACTTAGGGGACACATGGGACAGTCTAAAGATTTTTGAGAGCtacattct +attttttcataaaatttccaacatgtTGAGCCCCATATCGACTATATTCc +aatcaatttgaattttcagaaaattttggtgcaaatgcgctccaatgcga +aaagtgaaaatttttgaaacccagccatgattatacttattttgtcAGCC +TTAATTAGCTAAATTCAAATCTTCTAATTTTATTGCTCTAGGGGCAAAAT +AAATCGAGTTATGACAGTTTTAGTGGTGCTTaatttttgctaaaaaccGT +CGCTGACACTTAGGGGACAAATGGGACAGCGTAAAATTGTTCGAGAACTA +TAATCCAATTTGACCttaaatttccaacattttgagccccatattgaaTA +TATTCCggatatttttaattttcaggtgcAAATGCGCCCTAatgataaaa +aaatcaaactttaaGGAATATAATACTAAAATATaatactcaaaatttca +gaaattttgtgagaaaaacAAATCTGTTGTTTGCTTTTTCAGATAACTCG +CTCTATTgcactttttttctcaatttccgttTTAATCTAACTAACGTTTC +CCTGCCTTATTCATTCGACACACATCAAGTTGGATGGAGCAAGTAAATTA +ATTCTCTCCCTCCCTTCGCTTTCCCACGTTTCCCTATTtctctaagtctc +gcttctctttctatactctctcgatgtctctgcgtctctcctccctcttt +ctctctctctcttcctaaTTAATTCGACACGAGACACGAAGCACCCAATA +ATCCATGTCCTTTTTCCGTCCCGTTTCTATTGGTCCCCTCCCCATTTTCA +TCATTGAACAggcagaattttcaggatgtCATCTGAAGCGGCTCCAGAAG +TCGTCTCGGCCACGGCCTCCACAACGCCGGCGGCCACGCCCCCTTtgaaa +gggggcggagttCCGGGTGGTGGTGGGACAACTACCGCCGAGCAACAACA +AGTCCCATTTCGTAtgtttcatttctttctttttttaaaacaaaattttc +aatagtttatcgATAAAATGGACGGTTTCACTTCAAGCGCGCTCcaattg +caaattttgagaaaaatgaaaatttttgaaacctagtcatgattatactc +attttatcTGTCTTATTTTGCAGATTCCGAAACTAAAACTTTCATTGTTC +CAAGTGCAAAATTAACCGAGTTATTGtaattttaatgaatttaGTCAAAT +GCGCCACATTGctaaaaattaacatttttggaactaaaccatgtttatac +tcattttatcTGACTTGTTTTGCTGATGACACAACTGTTTTCATTGCTCT +AGCTGCAAAATGAACCGAGTTATAACAGTTTTAATAAATATGACCAAGTG +CGCCCCATTGAGAAAAACTAGAATACCAGAACCCAGTCTTGATTATACTC +TTTTTATCTGGCTTGTTTTGATTATTCCAAAACTAACAAGTAAAATTTTC +TAGGTGTAAAATGAACCGAGTTATGGCAGTTTTAAGAAACTTGACAAtat +gcgctccattgacaaCAGACACTTAGGGGACAAATGGGACAATTTCTGAT +AACATATTCAACTTTGTcatgaaatttccggaaatttgaGCTCCATATCG +ACCTTATTCcgattattttgattttcgatcaAATTTACCAGTAGGCCGCG +GCCTCGGCTGcggtcgaaattcaaatttcaaggaaTATAGGCAATATTat +actcaaaatttcacaaattttatgGAGAATCCGAATCTAGCACTTATTTT +TGATAGATATGCgtctatagaaaaaaaaattgcggggttttccaaaaatc +cgcaaaaaaatttcgtgaCTGTAAACAAGAGATACATATTTTCAGGAGGC +TTCTCACTGGAATATTAAAAATTCCTCGTTTTTGGTCTGTAAAAAAGCCA +AGAAAGACGATGTCCTCTATTATTTTCTTGTCTTGTTTTCTCCTCCCATC +GTCCCCAACAACAAAGAAATAGGCTATTATTTATGTCGCCTAACCTAGTC +GCCTCCTGTCACCACGGAAGAGAAAAtagacatttttgtttttcagggGA +AAAATTATGGAATCTTCTGagtcatcaattttttctctgttttgaaattg +taattGCCTATTTTCTTGATTAAATACAAtaattttctataaattttgtg +aaatttagaGTATAATCTTGCCTATATTCctcgaaattcgattttaggCC +TGGCAGGCCAAAAATCCGCGGCTTAAAGAGACAAAAAGTGCAATAGAGCG +AGTTTCGGCTAGCTCCGGGAAAAACAAACACCAGATTCgtttttctcaca +aaatttctgaagttttgagtaTAATAATGTCCATATTCCTTGAACTTTGA +TGTTTTCATCATTAGGGCGCATTTgcacctgaaaattcaaactaatCGGA +ATATagtcaatatggggctcaaaatgtgGGGAATTTTATGACAAATTGGC +TTATAgaattcaaacaatttcaCGCTGTCCCATTTGTCCCCTAAGTGTCA +GCGACGATTTTTACCAAAAATTAATCGCCATTAAAACTGTCATAACTCGA +TTTATTTTGCCCCTAgagcaataaaatttgaagatttgaattcAGCTAAT +CAAGACTGACAGAATAGATATAATCATAGCtgggtttcaaaaaactttca +tttttcgcattggagcgcatttgcaccAAAATTTTCTGCAAATTCAAACT +GATCGGAATATAGGCAATATGGAgctaaaaactttgaaaattccatgaCA +AAGTTGAATATGGTATCAGTAACTGTCCCATTGTCCCCGAAGTGTCTGTT +GTCAATGGGGCGCACTTGCtcatttttattaaaactGTCGTAACTTGGTT +CATTTGGCAGCTAAAGCAATAAATCTTTCAGTTTTGGAATTAGCAAAACA +AGCCAGTTAGAATAAATATAATCATGACTGGGTTCTAGGGATTTTAGTTT +TTCGCAATGGGGCGCACTTGTTAATATTTAGTAAAATAACTCGGTTCATT +TTTCACCTAGAGCCATAAAATTTGCAGTTTGGAAATCAGCAGAACAATTC +AATTCAGATGAATTTAATTATGACAAGCCATTGAAAAGTTTAGTTTTTAt +cagtagagcgcacttactcaaaatttttttaacttaaCTCGGTTTATTTT +GCATCTAGATCAATGAAATTGTCAGTCTTGAAATCAGCAAACTAAGCCGG +TTAAAATGATCATAATAATGACTAGGTTGCAAACGTTGAGATTTTCGCAA +TGGGGCGCACTTGCTCAATTTTATTAAAACTGtcataactcggttcattT +TGCACCTAGAGCATTAAAATTTGCAGTTTTGGAATCAGTAAAACAAGCCA +ATGCATAATATGCTCAATAGAGGTTTTTCACTACttcaacttcaattttt +tcagaaatgattCCACCCGGTCACTTCTTCGCGAATCCATTCATGAATCC +ATATGTGCCATCAGGTGTCCCACAGCAACAAGAAACAGGAGGAGAACCAA +GTGGCGTGCCTCAACCGAATCAAATGGTTTTCTCGCCGGCACAATATCAA +GAAGTCATGCATCActattttcaacaaatgatGGCCGCCAGTGGAGCGCA +GTTTCCCATTCCCTTCCCTATGCAATTTCAACCGGCGTTCCAACAGCCGC +GACCTAGTTCTCAGGTTTGTAGCGCAAACGTTAGAGGagctatgaaaatt +ttgtaaattgtaaactgtgtaaaattttatgctctttaatttgttagttg +acaaaaatttgattggagctttagtttttgagatgcaAGCTTTTGAAGAG +GACTAGCTACAAGCTCTTGTAGGAAACATTTCTTTGAACACCGATATCTC +AATAACGAAAACAGTTACCAAGATTTTGTAAATTCAAGAAATGTgttaaa +ttttaaaagctaTATTTTACTAGTTTAAATTTTTGCCTAGCTCTATTGGT +TTTTGATATAAACTCGTTTAAAGTCAAGTGACATTATGGTGCCTTGGTTG +AGCCACCTGAACGGCGCTCTACTTTCAAACGcctttatctcaaaaaccaa +catAGTTAGGTAAAATTTactaactaaaaaaatgtgtaaaatgttGTCCT +Ctccattttattagttgacaaatttttgctagaaattttagtttttgaga +tacaagcTTTTGAAGAGTAttagttccaaaaattggtGTATTTGCGGTGA +AGCTTCTTTGAACACCGATATCTCAATAACAAAAACAGttaccaaaattt +tgtaaattaaaaaaatgtatgaaattttataagctaTATTTTACTAGTTT +AAATTTTTGCCTAGCTCTATTGGTTTTTGATATAAACTCGTTTAAAGTCA +AGTGACATTATGGTGCCTTGGTTGAGCCACCTGAACGGCGCTCTACTTTC +AAACGcctttatctcaaaaaccaacatAGTTAGGTAAAATTTACTAACca +agaaaatgtgtaaaatgttGTCCTctccattttatcagttgacaaatctt +tgctagaaattttagtttttgagatacatgCTTTTGAAGAGCACTAGTGT +TACAAAATTTGATGTCTAGAATTATTTGGTTCCTCTTAGTCATCCTTTTT +CGCAGTTTCAACATGATCTATTTCGAAATGTCTATTTCTTACGACGTGCA +ACaaaaaaaGGGACATAAAACATTTCGCAACATGCTCCAAGAGTCCTTGC +TCCCAGACATCAGGACAAACCGACAAACAGGCAGAAGAGTATACGAAACC +ACTTGATGATCTCAAGAGACATGTGTCCCTGTcccattttctattttgtc +AGTCATCCCCTCAAATGACATTCATCTGTGCTCTCCTCTTTTCATAAATA +CATATAAGTATCCTCCTATTCTTCAGGCATCATCATCTCATCGCTCAGAA +GACGATAATGGAAGGCAGACAGCTGGCAGTATGGGTTGTGTCTCGTCGAA +TGTATCACCAAATCATCGAGAGGTTCGTTTAGAAACACTtgagaatgaat +aaaaaagaagaaaaaacaatattgcctctagtggggttcgaaccccagtG +GGCTAAATTGAGGGCGGCAGCGTTAGCCAGTAAGCCACGAAGGCGCGCAG +GAATTATAGGTGTGCCGGGCGATTAGAAGGGAGCGGGTCGCCAAACTTTT +TGAGGAGCGTCGGGGGGCCATCGTGAGGTGTAAGATAGTTCGCTCCAATG +AGAACAACTGATTTTTAAGGGAATTTAGTGTCTTAAACCGTTCAAAGACG +AATTTAAATCGAAATTAAgttattttcagacgaaacCAGAGGGATCTAAG +GAAGCATCAACGTCGCCAGAAACTCAGGAGCCTGTTGTTTCAAATTCCGC +TGGTGagtattttttctagtttttgatatatgttCCCCCTTCTCTAGTAC +TCCTCTAGTGTCCCAAAAGAAGGCATCCTGAAACACAAGATCATCTCCCT +CTCTCGCCTTTTGGGCGGCTCAACGAGagattttctctgcgtctcttgtc +atttcactctctctctctcgcacATCTCGTTTGTCGATTCTCCACTAATT +GTTCGATGTGTGTATGTATTTGTGGAACGAGAGAAGATGTTGAGTTGTAT +CTGAGCAGTCAGACTACTTTTTGAGGGACCTGAAAAGCCAACTTTAGAGC +TAATTTGCActaaaaaagtattaaaatttgagaaaaatgagataaaaacC +CGAAATTCCTTCATAAACcactatgaaaaaaaaacgaagacaAAAAACCG +CCGGTGGGTGTCGAACCCGAGACTTCAAAACTAAAGAGCAGCAGTTTTAG +CCACTAGGCTACGCGCGCACAGTTTAACTGTGAGAGCGAAGGTAATTAGG +AAGGTGGTGGTCGGCGCAACTTTTCAAAGGAAAGCGAGcggccaaatttt +ttttgtaatgtaAAATTAGGAAATATGAAAACGCGCTCTGCTGACAATTA +CTAAAAATCAAGCGctaaattagaaatttttcagaagacacCCTGGTTCC +AACCTCCTCTGACGTTGCCGTTGGCGACGTCATTTCGGGAGAAGCGTCTC +CAgaatccacgtcatctggagaagagaaatcggaggagaagagaaagaat +tCCGGCGATCGAACGGATTCGTTGATTCGGAAACAGATGAGCGAAATGGA +AAAGGAGATTACAAGGAGGTCGCAAAACAAGAATATTAAGAAGGTAAGTG +TAGAATTAGTGTGAGGAAGAGGGGCTCTACAACTTAAAATAGATGtacct +caaaaactagaggagctagcaaaattttgctaacaaacaaaataaaaagc +gtaaaattttatacatttttgcagttgaacacttttttctatctatttta +gtttttcagatacaaGCGTTTGAAGTTAAAAGATGGTGTCTTAACTTTAA +GCGgatgtatctcaaaaactgtaattgcgagcaaatttttgtcaactaac +aaaataaagagcgtaaaattttacacattttcttagttgacaactttttt +ttaaaagttttagtttttgagatacgccGCTTGGAAGTTTAAGCGCTCAC +TTTCCACTCTCAATACGCCAAAAagcgagacactctagcttctctgcgtc +tctttttccTGGAAGCTGAGCTAGAGATTTCAAGAACAATCCACTATTTC +CTCCCCTAACCCCGTCCCCTTTCTCTCCCATAATCTAATAACGGtcccat +tgctcattttctctggtccctcttcaaaaattctgctctctctctcttct +tcagATGGTCCCTTTCCATTCCcaaatccacaaaaaaaagCACACACttt +ttcactcacttctttttttttcccccgattttctcctattttttcactac +tttttcaaaaaaaaatgggaattaaaaaaaaatttttgagttcaattttt +agctattaGCACTAACCATCACTTTAGAGGACTAATTGAGGAAGGTTTAA +AAGTACCATAACTTGGATAAACTCAGTCGGAAACTCATCAtacttatatt +tttcaattcagcaagtcaatagcttcaaaatgagtataaacaagccttTG +TTTAGAAAagtgggtcccaccacgaaaactacagtagccctGAAACTCTT +CCGAAACtagccgtgtttatactcattttgaagcgtaTGAACAagccaat +tcaaaaaatttaaattcattCGAATTGAGCCAAAACCAACGGAGATATTG +AACAAATTTGAATGTTcgctgattttcaaaattcaaatgacCATAACTCG +CTTGGTTTTGACTCAATTTGAGTGAAACTTATTTTGTTTGATTTGGCTGa +ttgtgagcttcaaaatgagtataaacacgcctaTGTTTAGAAAAATGGGT +CCCACcgcgaaaactacagtaacccgctAACTCTTTCAAAGCTAGctttg +tttatactcattttgaagcgcttgacaagacaaatttaaaaatatcagTT +TCAAGCGAAAACGATCAAAATGGTTTGAGTTATGgacattaaaaaatgtt +taaggTCTAACAAATCGCTTATGggtttttcgggaaaattttcggtttct +taACCCCTTCTACACTACCCCTATCTATGCAGATCGACGACGACAGTTTG +GCGGAGCTCATCGGAGCATCGAAACCCATCACTCAACTAACCGCCGACGA +TTTTTCACCGTTCTCCGAGAAGGTACCACATCTCGTTGTGATTGTCTCAA +TTGTGCTCCATCGCGAATGTTTATCAATGGAGCACAAGTTCCCGCATGTA +CTAACCCGTTGTGCACCTTTTAACTTATTATCTATGAAGCGAGTTTTCCT +ATTCTATTGCTGTTGTTGTgcgattttcgaaacaaaaattgaattcccgC +CTGATCAACACTTTTCCAGAGCGGTCTACCGTATACCGCACCTGCTGTGG +TTGAGAAGCCAGCTCCAAAGGAGTCTCTAAACCAACTACGCTCATCTTTC +AATCTTCCCGAAGATTCTCCGACGGTTGGACCCGTCGGACCCGCTCAGAA +TACGGTACCTGCGGCCCAATTCGCTAATAACTCGATGTTCGCCGGGAATT +TTGCGCAGAACGCAGCATTTGTACAGGTAtttaaaaatatcgatttttga +agaattggcgagaaatttgaatttttcagatgactcCACAAGCTCCATTC +GGCACCACGCCAGGCTTCCAAATGATGCAACCACACCAACATACTCTTTT +CATGCAACAACCTAATCGtaagtgatttttcaaatgcgctctattgcgAA +TTTGTCAAGTGGAGCGCGGTTGCTCGAAGtgtttttgtgaaattcttact +aaaatcgatttttgtcgattttcgcTTATTTTTGCTGATAAAAGTAGTTC +TTTTCATGCTGAAATACACATTTtaagtggaaaaaaaaatcaaaaaatcg +ataattttttgaaaatttccgattttctctctcatttttctaccGAACAA +ACTGTTTTTGCactcaaaatgtttgtcttagCCTGATGAACACCAGTTTG +Tagcaaaaagttcgaaaaaacgacgaaaatttctgaaaattggctgaaaa +ccaagtttccaaacaaaaaaattttgtcgcCGCCGCAACCGCGCTCCACT +GAACTGGCGAGAGTGAGTGGTGTTCTATACGCCTTGTAGACATAGTTCCT +TCGTGTGCGTCGTGGTGTAGTGGTTAGCGGCATTGCTTTAGGAACAGTGG +CTCGCGGGTTCGAATCCAACCagggaaaaaatgttttttttgctcttttt +gaagGCGTTAGGAAAGTTTAAAGcattcagaaatgttttttttttcaaaa +ttctaaggtctcgagaaaattttgtcagGGGACCAAAACAAATGCTTTTA +TTCATTAAAtaaaagtttattttcagctaCCTTCGTGAACAACGGGACCA +ATCCATTCCTCCAACAACAACCACCCCTTCCCAACTTCGCCAACGGCACC +ACTCCACTTGTACCTACAGTAACCGCTCAGCAATTCACTCCTGAGCAACT +GGCCGCCGCATTTGCTCAACAACAAATTGCTCAGCAGCACATGCAAGCAG +CCCCAACACCATTCGATGCTCCGCCCCCttcgacgtcatctggaaCCACC +ACGTCATCAACTGGTCTGGcaccacctccacctccaTCTCATCCGATTCA +TCGAAAGAACTCGGGTTCTGGATGGCCTGAAGAGAATAAGGAGAACGGGA +CGTCGAATACTAGCACGACGTCTAACGGAACACCTAATGGAGCACCatcc +acgtcatctggaaCCGAGGATCCAGTATGGGTTCTTCGGGATTCGTACCT +CAAAAAGATGCAGAGGGAGCAAAGGACTTCCGAGGAGGAGGTATGTTGTA +TATGCCTTGCGGCATAGGGAGAAAGTGTGTAGCGCGTGGTGTGGTGACTA +GCGACTTTGGTTTTGAAGCCATGGCtcgcgggttcgaaccccatcGAGGA +CCATAAggtccaaactttttttttgcttctttttagAATAGTTATCCATA +GTAGAGTTCTTTCTACAAACCAAATCTCaagtttttacaatttttcgagt +ttggaactctttttaaaaaagttccaaacTTATGATAATGCGATATAAAA +ATGAGTGTAGTATATaaagaaaagcagaaaaaggaaataatgACACCCTT +GAGAAAAAGATGTATAGCTGGAGAAAAATCTGAGGAAAGCCGGAGAAATA +TTTCCggaacttttttccttttttggattttttgaaaatttggaatcttt +atttttaaaggttctcaatttcagatttcagattttctagagaaatattg +atctttttttttaatagaaataatgacttttcaacatttttggatttttt +agtttcccAGCAGATGGCCCGCCAATTTTCACAAACTCACATAAACCTAA +ATAATCTTTATTTCCCTAAAATTGATTAAAACCTTATTCCCATGtcctga +aaaagaagaaaaaagaaaaaagctcGGATGGGTTCGAACCCTTGGCCTCT +ACCTCAAAACGCAAGCGCGCTACCACTGCGCCACACCACCACCAACGAGG +AAAGAGAGTGGAAAGCATAGAGAAAGGCGTGCCGTTTTGCCGCTTTTCAA +GATAGATTGATGCGCTTGAGCATTTTCTCCTTCCAAAAAAGTAATGAAAT +TCTCTTAATTTCCGGTCCCCAATTTATCTTTTAAAACGGATTTTTCCATT +AAAACGGTTTTCTCTGCAGGAAATGAATTGGCATGAAGCGGCGACAGCTG +CACAGGAAGCCGCAGAAAATGGGGCTGGTGATGAGCAAGAAGAGCAAGAA +ACCGATAGGCTATTGAATGGAGCCGGTGGGGGACCATCAAGCGGAATTAA +AGGCGCACCGGGTACGGAGAATCGGCGAGGAAGTatggataagaagaaga +atagcaaagagagtgagttttttttcaataccgTTAACACAAACCCCCtt +aactgtcaactttgagccaagttatctcggttcctgtgagagatatcaaa +aagtgatcaaaatgttgctgatattatgataaacattttgtcagttgacc +gttttttgatacctttcacagcaaatgagatatttgagctcaaagttgaa +gggtTTACGGTACgtttaaaaaaagttgaaaagttggAACTGACTAAAAC +TGTGTTTAATAAGTATTAGTGTggttttctaaaactttcaatgcagtgga +ttttcagtttcaaacgaaaaattcaaaaaaaaagtcaaaaaattcaaatt +gaccAAGCGGACCTTCTGCACTTGTGTTGTCATCTCCTATTTTCTCTTAC +ACACACCTCTAGTTATTATTTAGTTTtattagaaaattattttcaaaaaa +aaagattcttgaaactcaaaaaaccccCTATTACATCGGCACCCACATAC +ATACGTCCTATGTCTACACACAGTAGTTGTTTAAAATAATTTGGTGAGTT +ATCGTGATCTACAGTACTCCCTGCTaggagtacagtaatccttcaaaACT +ATGGAATGCGCTGCAAAGTCCCTCTCCCTTGATGCACTGTGGCTTTTTCT +GGCAATTCCTAAGTATTCAATATATGCCTTTTTAGTTggttttctttcat +tttttctgcatGCCAAATATCACTATTTGTTTATAGTTTCCGCAGCAAAA +CGAGATTCCATACTTTAAAAGAggatatctcaagaaccatcAGAGCTaga +caaaagttttcaattaacaaaataaagagcataaaaaatgacatacttta +tcagttgagctCTTCTTTctatcttttctattttttaagaTATAACCGTT +CCAAGCAAGCGCGCTCCACTGCAAGAGAGATCTTACCGTAAACAAGGTAT +ATCTCGATAACTATTAACGctaaacaaaacaattcaacaacaaaaatata +gctcatcaaattttacatattttgttagttaatacttttgttctatcttt +tttagtttttgagatacgacCATTCCAAGCAAGCGCGCTCCGCTGCAAGA +GAAATTACGCGCCTCACTTTAAACAACGTATATCTAAAGAGCTATTAAAG +ATAGACagaaattgtcaactacaggAATAAAGCTcattaaattttacata +tttcagcaattgatacttttttttctagcttttttagtttttgagataga +aCTGCTCTAAAGAGGCATAAAACGCGCTCCACTGGTTTTATGCGTCTTAC +CTTTAACCGGGTATaaatcaaaaaccaaaacagtTAACAAAATATTATGC +ATCACAAAAATATAGCTCATAAATTGTtatacattttgttagttgaaact +ttttttctatcgtttttggtttttgagatacgacCATTCCAAGCAAGCGC +GCTCCGCTGCAAGAGAAATTATGCGCCTCACCTTAAACAtggaatatctc +aaaaactatcaaCGCTATACAAAAATTGCgaactacaaaaaaatagctca +taaaattttacaaattttgttagttagcACCTTTCTTCTAGCTTTCTTGG +TTTCAGTGATATTACCTTTTAAAATATcatcaaatattcaaattttagtt +tttgagatataaatCACTCTAACACTGTGTGTTTCTTACACCTCTATCCT +ATTTGGCTCTATTggccccgccccttttcaAAACTCGGCTTATTGATCGA +TTTTATAATTTCTCTTTCTATGGTGGTGGCTTAtttttttGACGAGTGAA +CCGGACCCTCTTCCCCCCTCTCAGCTTATAAGgcatccaaaaaattcaaa +ggtttcggcgccaaattcaaatttttgttaaaatttcagcaatgGTTCAT +GAACCTGCAGTTCTCATCGAGGGTGTCCTGTTCCGTGCTCGATACTTGGG +CTCAACTCAAATGCTCTGCGAATCGCGTGGCTCGAAAGCGGCTCGAATGG +CTCAGGCGCAGGAGGCGGTGGCGAGAGTCAAGGCGCCAGATGGAGATGTG +CAACCGTCGACGGAAATCGATTTGTTCATTTCGACCGAGAAGATTATGGT +GTTGAATACGGACCTGCAGGTTGGTCgggaatttttggttttctagctTT +TGATCTATAATGCCATAAAAACTATGCAAAATACCTCCCTcagaaccgtc +aactttgaacccatttatctcgatttctgtgaaagatatcaaagaattgt +caactgataaaatatgtatCACATTATAAtacacattttgtcaattaacc +gttttttggtatctttgaCTAGAGCCGAGATAAACTTAATCAAAGTTAAG +GGTACCTTTTATTGGTATAGACATTTGATGTTGGGCCAACTTTGGGTGGT +TATATCTATAAAACGAATTTAGCTAGCTAAactttgtaaactacaaaaat +gtagctcatgaaattttgcatatttttagtgttgacaaagtttttatagc +ttttttagtttttgagatacagtCCTTCAAAGCACAGCGCTATACTGCAA +GCGCACCAAGATGCCTTACCTTTTGCGGAgcttatctcaaaaactgaatt +agctaacaaaattttgttaactgacaaaataaaaaacactaatttttgca +tattttattggttattaacacttttgtcttaactttttcattttttgaga +tacaaatgttcaaaatttcagagaatatcCGACACCGATGTTCGACAGGA +CATTCTAATGGACCACGCTCTACGGACAATCAGCTATATTGCCGATATCG +GCGATTTGGTAGTTCTGATGGCGAGGAGAATGTCCACAAGTCATTCGGAT +GAAAGTTGTTCGGATGGGTAAGGATTACTGTGTGTTATCATTGTGACCAT +AAcaacccaattttcagcgacaGCAGCAGTGGAGGTGTCCGGAAGACGCC +GAAAGTCATTTGCCACGTATTCGAATCCGACGAAGCCTCATTCATTGCTC +AATCAATTGGACAAGCGTTCCAAGTAGCGTATGTGGAGTTTTTAAGAGCC +AATGGCATCGATGATCCGAGTTATTTGAGGCAGATTGATTATCAGGTAAG +CCcagttgaaaatcgaaaactttgaagccCTACAAAAgtgtttcacaatt +tttgaacttgtttaaaaatttcattgtacactaaacaaaaatagagcttc +atttttgtagttggcaagtttttcgtaaaatttgacctagaaaagatatg +ccacgtggaagagaaGATCCTCAGAAGGCGCGTCAGCGCACTAGCGGTGG +TGGCGCCCGAAGGCACCCacacttccacgtggcatatctcttacaggtca +aattttacaaaaaagttgtcaactactaaattgaagctctatctTTGTTT +AGTGTGCTCTAAAACTTTTGGATTGATCTGACAATTATTAGTTTTACTAG +CACAGGTAAAACGcgaacgggtccgttacggccgcttcgcgttcgcgcgc +ggttgaaataggaaccgcatacggacggcacgcgaaccgttttcagtaaa +tagcagtacattattcggattgatccgtattctgtccgttcgcgagctcc +gtatccgatccgattgcgaatcatgaccaaacagatccgtttgcgaactc +aataaaacatttgattnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnGAttc +gcaaacggatccgtttggtcatgattcgcaatcggatcggatacggagct +cgcgaacggacagaatacggatcaatccgaataatgtACTGCTATTTACT +AAAAACGGTTCGcgcaaccgcgcgcgaacgcggagcGACCGTaccggatt +gttcgcgaatcacctgtgaggaaacgtttgaaaattatagctgttttctt +caaaaaataaagatgTGGTTATTTTTCGACGGCTTCAAAAAGCGGCTCGC +ATTTGATAGattgataaaaaaatttcagagtatactaaccAAAAacagag +ctttaattttgtagttgacactttttttgtgaaatttaagactgaagaga +tatgccacgtggaagaagGGGATCCTCAGAAGGCGCGTCGGCGCACTAGC +GGTGGTGGGCCCGAAGGAACTCACACTTCCACGTTTCATATCTCTTTTAG +gtcaaatttcacaaaaaagttgtcaactacaaaattgaagctctatctTT +GTTTAGtagactctgaaattttcagacaaattcaaagaaattggACCACT +TTTGTAGGGCTTCAAAGttggcgattttcagctaaaaatagttaaaatca +aaaagatactgtatctcaaaaacgagaATAGCTATCATAAAACggttaac +tagaaaaatgaagctcataaaattttctacaattaACTcttgtttttaaa +gttttttgacacaattttttgtattttcaggaAGTGCTAAACTCCCAAGA +GCTACTTGGTGACGAGTTGGAAATGTTTGCCAAAAAGGAAACCCAAAAAG +AAGTGGTGGTCCCGAAAAAAGCCGGTGAACCCCTGGGAATTGTTGTCGTG +GAGTCTGGATGGGGGTCCATGCTACCTACCGTAGTCCTTGCACACATGAA +TCCCATCGGACCGGCCGCCCACTCGAATAAATTGAATATTGGAGATCAAA +TCATCAATATCAATGGAATCTCGCTCGTTGGATTGCCATTATCAGCTGCT +CAGACGCAAATCAAGAATATGAAAACTGCGACGGCGGTCCGGATGACGGT +AGTGTCTACGCCGCCCGTGGTGGAGGTTAGGATACGACGACCGGATACCA +AATACCAGTTGGGATTCTCTGTGCAAAACGGTGTCATTTGCTCTTTATTG +AGAGGTaaggaaactttgaaatttttaaatttgaatttggcgcgctaaga +gcttcaaaataagtataaacacaCCTAGACTTATAAAATTGGGTCCCACC +GCGAAAACTACAATAATcctcaaactttttggaaagtagctatttgaaaa +atactcattttgaagctcgtaacaagcgaaatctgaaaaaattaattttc +ttcaaactGTGCCAAAAATTACtgagatattttgaaaatttgaatttttc +acaaatttcaaaatgaaatagatcataactcgcttggttttgactcaatt +tgagtaaaactttttttgttcaattttgttcattgtgaacttcaaaatga +gtataaacacgcctgaaattacaaaattgggtcccaccacgaaaactaca +gtaatcctcaaaatcttctaaaactagtcgtgtttatactcatctTGAAG +CGCCTGGCaaggcaaattcaaaaatatatgtttCAAACAACTCAGATCCA +AATTTAATGAGTTGTGATCTTAGCAAAGTTAAGAAAACGTTGCCTTTAAC +ttacggattactgtaattaatTACTGTACAAAGTCTTAATCAAACATTTT +AGGCGGTATCGCTGAACGCGGAGGAATTCGCGTCGGACACCGAATCATCG +AAATCAACGGCACGTCGGTGGTAGCGGTGGCACATGATAGGTGAggctaa +aaaatcgataattctgaaaaatcgataatttttcagaattgtgaATATGC +TCGCCACGGCGGTTGGAGAAATTCATATGAAGACGATGCCGACGTCAATG +TTCCGATTGTTAACGGGTCAAGAACAACCACAGTACATTTGAgaaaatcg +attatcgattttttttctttttttctttttttctctcttccctcTCCCAA +CACCGCACTTTCTCTGTGATAATcatgttttctttctttcttctttttct +cttttttttaaagtgaaaatgcgctctattgagggttttgaaattctcaa +aagagcgcattttcttcttgaatttcagtttctaGGTGATTCTCTGCGAG +TCCACATTGCCatgtttttttgctctttttttcgaaattttcagtttttc +caaaaaaaattcattcattttttttcaattggtcacaatcgggatttctc +tttcttttttcgtctttttctcaattttttttgaatcttcggtaatttaa +taaaatagatttttttttcaaaaaattggtttaaacattttcaaaattta +agaatcctgagaatcctatgaatccaaagaatccaaagaatactgagaat +cctaGTAATAGTGGGATCCCTAACTTTGATCCAGTTTATCTCGGGtcctc +tgaaagatatcaaaaagtggttaactgataaaatgtttatcataatatca +gcaatatttcatcagttgatcactttttgatatattgtacagtaaccgag +ataattaggttcaGAAGAAGCAATCTTCTTAAGGAGATTCGCACctttca +aaagtgaaaattcaataattattcaaagttgattttaaaaaattcgaaaa +attaagaatatcgaatttcaacaaaacgaaaacgactacgtgattttttt +tttcagaaacccacGACCCTAGATGCCCCATTGACCTCAGGAGGAATACt +ataaaaaaagaggaaagtgtagggaagaatcagttctccctGCTCTGGGC +TCCAGAGGAGGTGACCCGCGGGATCCGGGAACCAGACCCAAGGGGTCCTG +GGGTCAgtcggcggctacaatctTCTGGCTAGACTATGTAaaatctaggt +cgtgacccaaaaaatctaggtcatgttccgaaaaatctaggtcacgaccc +aaaaaatctaggtcacgacccaaaaaaatctagatcaggacccaaaaaaa +tctaggttacACCCAGGACCCAGGTCCCGGTTCCCGGCCACAAGACCCCA +GCATCCCCCGGCTCCCCCTCTCTGGATCCCAAAAAAGGGAGAACTGATTG +TTTTCCCCGCTTCCCTCTTCCTTTATAGCACTCTTTCCAAGGTCAATGGC +CTAGGGtcaaggatttttgaattcttttgaaaattggtttttgatcacgt +ttaaaaaattattgaatttccacttttgaaatctgtgaaactccTTCCAA +AAGGTCGCtcctttgagcccaattatcttgattcctgtgagagatatcga +aaatttgtcaactaataaaatgttggtgatattatgttaaacgttttatc +agttgacaggtttttgatatgttttgaatgagccgagataatcaagctca +aagcgCATACATTCTTTTAGAGTATAAGTTACCGTAACTTCTCTAATGGA +ATTTCGtgcccaattatctcgattcctgttagAGATACCACAAAGTAgtg +aactgataaaaggtATTTCATAGTAtcgccaacattttatcagttgccag +aTGTTTGATTTCGTTTCTCGAAACTGAGATATTCAAGCTCAAAATGGAGG +CTGCAAGGTGTGAAGCTCCTTTAAAAGATTGCTTCTTTtgaacctaatta +tctcggttactgtaaaagatatcaaaaagtagtcaactgataaaatgatg +tttattatgataaacattttattagtttactactttttgatatttttcac +aggagccgagataaactggctcaaagttaggaaCCCTAATATGACGggtt +ttcttaaaatttggtatcatctgaaaatggcaattttttgatgtaaaaaa +aatcaaaatttcaaaaaaaaatgacatttttcttaaaatcagaacctcag +aattccagaattttcaaaaattagatttttcagattttcgattttttttt +tagaatttcagaattctctataaaattgaaattttcgattttgcgaacaa +tttttgaattattcggcattatttttctagatttttgggGTTCGGagact +ttttagaatttctcagaaatcttaaaatctcagaatttttaattttcgat +cGATTTTCTTAAATACCAATTATCAATTAAAcgaatttcattttgatgAG +CACACAGCGAGAGAAAAGAGCAAGAGAcgaaaatatttagaaaagagaca +cagagggggggggggggaatttTCCGGGAATTGGGAATTTAATAGTTAAg +aataaaaatcgataaaaagagaggaaaacaTGACATATTACTACTTTACA +AACACACACATATTTGATGGAcggggggcggagcttattgGGGGGATGTT +ACAGTAAGAAAAGTGGGGCGGagcggaaattctaaaaaacccgttgtaat +agaaaaaagtatgaaaaattaTAGGGTAATTAAGGGATTATTTTAATtat +aaacgaaaaaaagagaaaaataaaatttgaaaaaaaatgaaaatgagaga +ttCAGGGTcaaaattacgattttcagatgatttttcagagcattttcaTC +ACGAAATCTCTCATTTTCGCCACACAAAAAAGGGGGAGACCCGAAGACAC +ACATATGATAAAATGGAATAATCAATCACAATATTAAAATCAttcgaaaa +agagaatttAAACCGCCACGACGGTGGTTCTTGGCGGCATAATGCCCATG +CTCAAAAACGAGATCGTCTCCTCGGCATTCGGCTCATTGAGGTGCTCAAC +AGTCATGTGAAATGCCAGCTGGGAGCCTTCGTGCGAGACGTATTCACACA +ATGGGCACTTGATGATGGAGCCAGATCGTTTGACAATCTCCTCGGGCGTT +GGAGCCGCATCGgcgttctgaaattcaaaaaaaagttaggaaatgcttag +gctccgcccactattccctgaatttttttgggcaatttcaaaggcttttt +aggtttaaaaaaatgcatttttttctgctgaaaattgctgaaaatttatt +ctgaaatctaaaaaaatataagcgtttaggctccgcccacttttaccAAA +ACTTTTTCGGGCAATTGTAAAGGcgtttttagttcaaaaaatgcattttt +tcggctgaaaattgtcacCTCGCGGGttcaaaattagcaaaaaGAGTCTC +TAATTTTCactgtcaaaaatattctgaaaagcaacaaaatgaatttctga +gcatttaggctccgcccactttcagaTTCTCGACACATAATTTAAGAGAT +TTTAAACTATATATCACGGAATCGCACAGtgtgcaagtgcgctccactga +tagccaagaaaaattccgcatttttaaatttttcagcagagcgtattcgc +ttttttgaaggcaattttaaggcttttttCGTcggaaaaatcttaaattt +cagacaatttctatgagttgaaaattctcaatttccacaGGCGCCAAAAA +GTTCACCTTTTCAAGCCTTCAGACGTTTATTGTCTGTGTGTCCTACCTCC +GGATTCTGAATGTGTCCGTGCTCGATGCGAATCTTCGTCGCTTGAATAAT +GCCGCGAAGCGTTTGATCCTTGACCGAGTGATGGTGCATTTGGTGGAAGT +CGACGACCGACTTGCACGCGTCCGAATAGTCGCAAATCTTGCATTTGTAC +AGTTGATTCCATCCGTGACGATCCAAATGCTCGATGAAGACGCTCTGAGT +GACACACTTGAACGTGCACTTTTTGCAGTGCTTCGCATTCTTCGCCACCA +TCAAATGCTTCATTTTCGGCCGTTGATACTCGGCTTTCGGCGGTTGTCGC +TTCATCGAGACGCGAATTCGATTGATCAAATGAACGCGATGAATCGCCGT +GTGCTCTTTCAGCTTGTGCTCCGTGGTCGTCTTGAACGAGCAACTCGTAC +AGCTGTACCCTTTCACACCGTGCGGAATAGTGTCTCCCTTCCGTTGATGC +TTCTGAAGACGTGGATTCTTCGCGTGCCGCATGTCCTCGTCATTTCCGTC +GTTGTGCACTTTCAAGTGTTGAATTAGAGCCGTTGGCGTGATCGTGTTAA +ATGTGCACTCCGAGCAAACGAATGGGCGTGTCGGTCCGTTCGGCGAGTGG +AAGAATCGGTGGTTTTCGAGAATCTTCGCGTCCGGCGATTCGAATGGACA +GTCGGGGCATTTGATTggtgctgaaaatgagaattcggggttatttttca +tgtttgactccgccccttttagCAACTATGGAGCATAGTTTCATCTATTC +TACAATTTCAGAGTGTACTAAAATTAATCTAAAAAAGGCCTTAGAAGTca +tttggcctaaaaattagACTAAACCGCCAAAAACTGATCAGGTACAGCCA +AAATTGGACCGAACATCGGTCTAGATCGGGCCAGAATGTCTTAAGCTTGG +CCTAAAATAGCCTGACATGGCTAAAAATTCTAGGCCGTTACTAGGCCCTC +TCTGAAGTCATCAAAAATCCATTCAGGTAAGCCCAGGATGGCTTtaaata +ggcctaaaatatCCTAAATTTGGCCCGAAATTCCTCTAAATCGGCTCGAA +ATGTCTTGGAATTGGCCTTAAAATTTAGTTTATTTCTAGGCCCGAAATTC +GGTTTCGTTTCCAAAGTCCAAAATCAGTCTAGAAAAGCCTTGACTAGGTT +AATAGTAGGCTTTAAACGGTCTagaattggcctaaaatttaCGCTGtttt +agaatctcaatttGGTCTCCTAAGCCCAAAATCAATCCATATAGGcccaa +aatgttttaaaataggcttaaaacgACTTAAATTTGGCccaaaatagccg +aaaaaaCTCACCATCAACACCAAATTCGTCTCTGAGCAAATTGCGAATCT +TCCAGTGTCCAATATCCATCGGATCCTCGTCCTCCTCCATCGGCTTCACA +ACGTTCGTCGCTTCTCCATCCTCCTTTCCCTCGTCATCCTCCTCCATCTC +AGCCAACCTCATCAGATTCGACGAGCTCGACGACGGCGTCGCCTTTCCAG +ACCCGTTCTTTGAGAGCAGCGAATAGTTGATCTTATTCCTGGAGACTCGT +TCTGAGAGCTGCCGCGTCGGCTCGGGATCCGGCGATGGTTCAACCGACGT +ACGACGTCTTTTTTGAGCTGGAGAGTTGTAGATTCTGAACTCCTTATCCT +CATTCTTAACCTTGTTATATCTTGATGGTCGTTTGGAGGAGGATCTTGGC +ACTTCATCCTCGTCAtcctcttcatcttcatcttccaACGATTCTGGAtc +ctcttctggaaccttcacctcttgcttctcttgcttctccgccttctcca +acttcctcttctgcacctttctctccCCAGCCTTGTTATCCGGCCCCCCG +TTCAAATCAGTTAGCGACGATACCGGCCGCCCATGATGGTCCACTCGCTT +CACAAATGGAATCTGTTCCGTTGAGCCACCCATAGCCAGATGGACCAGAA +TGTGCTCCTCGATTTTCTTGGTATCCAGCGAGCTATACGTGCAGTTCGAG +CAGATGCTGTGCTTCGGCACACGACGATGATAGCGAGCATGACGCCAGAG +GCATCCAATGGATACTGTGGTGTAAGGGCAACGAGAGCAGTTGTAGATGC +GGTCCTTGCCGAATCCACGACGCGTTCCAATTGGGATTCCTTGATTGACA +ACGATAGGATGGGTTGCTCCTGATCCATTAGCCAACGAGTTGTTAACCAC +TAGATGCTGTTTCATATGATCCTTAAGACTAACAGGACGGTTGGTGGTGT +ATGTGCATTGAACACATCTAAACGATTGCTCTATATCGTGTCGCTTCTTA +TGACTTCTCATATCACCACGATACTTCGATGTGTACGGACAATCAGTGCA +CGCGAATCCTTTAATCGAGTCAATCATTTTGCGAGTGAACGGCTCGCCGA +GCTCCGGTCGCTTCGCCTTCTCCGCCAGACACCATTTATGAATGGATTTG +AAGAGATCCGTCTGCTTGAACTCTTCATGTTCCACATGCTTCGCCTTCTC +TTCGTCTGTCTTCATCGCGTGCTGCTCGGCCGCCAACTTTGCcgcttttt +cagccaaatccaCGCGATGCATCTCTTCATGCGCCTTCATCACCTCCTCT +CCTCGCGCCGTCCATGAGCACATTTTGCATTTGATCGGGTCGTTGGTGAA +GTGCTTCGCGTAGTGTCGCTGGCAACGGTTCATCGATGGTGCACGGTAGG +GGCAAACGTTGCAGCAGAATTCCACCATTTTCAGTGCGGCAAACTCTTCT +GGGGTTAGATTTGCTAGGGCTTCGGGGcggaaactggaaaattaagGCTT +GTTTAGGCTTGGTTTTTAGGCTGTTTCAGGCCACAATTCTAAACTATTTT +AGGCcgtttttagaccattttatACTTACTTTCTGACCATTCTAGTCAAT +TATTGAACTattttagatcatttctagaccattttagaccattttccgaa +tatttagATCATTTCTGGAtcattctagatttttttaaagccaTTCGAGT +CTAATCTAGTCCATTTTTGGATCATTCTAGACTATTTTAAGACCATTCTA +GATCATTTTTGGGCTATTTCCGACCATTTTCCGAATATTCTAGACTATTT +TGAGCCTTTCTAGACTGATCTAAACCATTTTCTGcctattttggaccatt +ttagatCTTTTTTCTGACCACACTAGactatttttcaatcattcCAGACC +ATTTTCGGGTCattctagaccatttttcaatcattctagaccatttttag +accattctagtctaattttagaccatttttcaatcatttcagactatttt +caaccattttagatcatttttcgaccattAGATTGCCTCCAgctttatat +tttttctagtctagttttcaatgattttcgactattttagacctttttta +gCGAGTTCTGAACCATTTTTAGCAGTTTCTAGACCTATTCTCGATCATTT +TAGacactttttggaccattctAGCCCATTTTAGAAAACTCTGGACTatt +ctagaccatttttggctcatttcggaccatttttgagccattcgAGTCTA +ATCTAGTCCATTATAGCCCATTCTAGACcattttcgagcatttttcgACC +ATTCTAGATAACTTTTAGCCCATCGAAAAATGACCTTAAGTTTAGGGCCT +ATTCTAGACCCCTTTTCAACCATTCTACGCCTCTTTTCGACGATTTCTAA +ACTCACATCGAATCAAACGGCTCATCGTCGACGTCTTCGTCCTGCTGAGC +GAAGAACAGCATCTGGCGCATCGTCGGTGCCACGACTGGCActgaaaatc +tcttttttggtTGTGCTGTGAATTCAGAGGCACTCTTACCGTGAGGAAAT +TTCATTGGCGCTGTCACAGCCACAGCGTTTGACGATGACGGTTGGGAGTC +GTCGAGAACAAGCAAcggaggaggaggtggagTCGCACCGATTCCCGTGA +AATACTTGATGTAGAACTTATCGCCAATGGCTTCTTTGAGATAGAACGTT +CGATGGAATCGATTTGGAGCCGTGAGGTGGTTGGTCATTTTGTGAGCACG +AAGAGCACCGAAATTGGTGGTACGGTAGCCGCAAGTGGAGCAAAGGAAAC +GATGGAATGGGAAGGCCTTTTTCTGAAATGCTGTCGTCTAGAGAAAAGGC +CTAAAAAGCCTAAAAGCCTATAACTTACCGCTCCATGCTTATTGGTCTTA +TGGAAAATCAACTGAGTGATCGACGTCgtcaaaaaatcgcattctCCAAT +GTTGCACTGCTTGTGTGGGACACCGTCAATGATCCGGGTCTTGTGAGATT +TGATTTGAGCCTGGAAATAAGGAatttaaggatgagcaatcctAAAGGTG +CTCCTGGAGCTCTAGAATCTTCGTCTAGGCCAAAAGCGGTCTCTAGAGCC +CTAAAGAAtataaggatgagcaattctAGCTGATACTTGTGCTCTAGAAT +CCAAGTCTTGGCCTGAAAATGCTCTACTAGAGCTCTGGAGCCATCCTGTA +GCTGAGAAACTCCTAGACCTTCTTCTAGAGCTCCAGTAGAgcattttcag +ttcattttcagactcgGTCATTCCTCTTACCTTAGCGATCAACCCAACTC +TCGCTTTCGACGTCAGTGGAATCAAAGGCATCTTCTCTTCCggcacgtct +tctgattcctcCTCAACCTTCTCGATTTGAAGCTCCGGCAtcttctccga +cgccttcatcttattcaacttcttcaactccttctgctccttcttctcct +tctccagacgcttctgctccggtgacttcttctcgtacttcctcttcttT +GGCTTCTCCTCCACCTCGAGCTTCGGTGGCGCCTCTTCCTCCTCCATCGT +CACGTCTTCAACCGATGTGTCCAGATCCTCCGGCTCTTCACCAGTACTCG +GATGATTTGGATCCTCCACCTCTTCAATCGTCACCTTTCCATTCTTTTTA +TTGATTACTTTCCGACAGAACTTCGGTTGTCCTAGCAAAGGTTTCGAGTG +AAGAATGTAGTGCTTAGCAATGAATCCCCTCTTTCGACACATGAAATGAC +ATTCGGGCTCTGGACAAATGTATCCCTCATCTAGAGTGTGTCCACGGAAG +TGTCTCTGAAGACGTGTGACCGATGAGCAAGTGTACGGGCATTTGGAGCA +TGGGACGCCGCGCTTCGATGTCTCCTTCTGAACGACCGGAGGTGTCTGCT +TCTGAACTACTGGTGGTGGTGTCACCGACGATGGTGCAGATGTCGTTGGA +AGAGATCCACGTGGTGATGGTGTGTCTTCTTGAAGCCTTCCGGAAGCTGT +GGTGTCATCCAAAACCGGCGGCAACGCATCCAGAATCGGCAACGTCTTCT +GCTGCTGCTTCGTATACTTGCGTGGCTTCTTCTCCTCCAGCTTCTTTTGT +GTTGGCTTTGAGGTTCTTCCCGATTTGCGAACTGCAAGATGGTCTGGAGA +CTCGGAGACCTCTCTCTCCTGATCCACTTCCCTCTGCTCATCTTCCCGCT +CCAAAACCGGCGGCCCATCGTCTTCATCCTCctcgtcttctggattctca +gCATCCAGAAGTGGTGCTGCCTCATCACCATCATCATCGTGACCTTCAGG +TGCTTCCGGCAGTGGCTCCACAGACAAATCTGGAGCCACCAGAGACGCTG +TGGACGTTGACGAGTCCATCGAGGTGTTCTGGGCCTCAGGTGCTGGCGCC +GAATCCGAAGAATCTGAAGCCGGAGAGCCGGCAGACGCAGCGTCAGGGGC +CGGAATTGCTCCAGCAGTCGTCACTGGTGAAATCTGGGGACTCAGCACAC +CGAACTGCTTATGAACGTTGTTGTGCCACGTCAGCGATTTCAGTGTTGCG +ACGAGAAGCAGCACAGCTCACACTTAAACTCCTTCCGCTCTTTGGTGTGC +ATCTTGGCGTGGTTGGCTAGGCTGGACTTGGATTCGTAGCGCGATGGACA +CTTGTGACACGCGAATGGACCGCTCAtctggaatttcttttttcggggtt +ttagactccgcccatttttgatgatttttgggtttctaggccgaTCAATC +TTGTGGCCtacgaattcgaaattttgggatttttaccGCGTCACAAGCTC +AAGCCTTTTCCGGTCTcatgtggcctagaaacccaagatttctaggccac +cacaaTATAGCCGAAGCTTCAATTTCCTGTGGCCTAGAactttggatttc +taggcggcctagaaacccaGGACTTCTAGGCCGTGAAAAAGGAATCTTGT +GGCCTAGAATCActaaatttctaggccaccagaatAACCAGCTTAGAGAc +gttgtggcctagaaacccaatttttcctacagtaatctcaccTCCACCCA +ATTATCATAAGTATCCTGTTGATATCCGTGAAACACGGCCGTACTCCTTC +TGCTACGCCGTCTACCATCCGATCCTGCTCCTCCACCAGTTTCCACATTC +AACTGCTCCGCATATGCTCCGCCTCCCGCTTCTGAATCATCCAAATCGTC +GTAGGCATCGTCGTCGGAATCTGCGACTTCGCCGTAGTCGCGCTTCCGAC +GCTTCTGATTGTTTCCATGGGCGGCGGCGACGACGTCAAGTGTGAACTTT +CGACGTTTCGATCGTCGGAGGCTATCGTCAGCCGATGCTGCTGCTGCTGG +AGCTGAAGGCGTCACTGGAGCCGATGAAGTCGTCGGAACAGATGACatcg +attctgaaagaaggGGGCGGAGTTTGGTGTGCTGTAGgagaggagagaga +aaagcgatgaaaaaagagaaaaaattcggtnnnnnnnnnnCGAGTAGTAG +GATAAGGGTTACGGTACTTCCAATCCTAACAAGAATTCCattgtctacag +taatccttttagCATTTGATGACCTAGAATTCCACCTAGGGGGATTTCTA +GGCCCCGCCCATATTTAGAAGACAAagggactgaaaaaaaacagaaacag +aagaaaaataggggaaatggctagaaggagaaggcgaaaaccgataaaaa +CGAGTAGAAGAGAGATACGgcagtgtctgcgtctcttcgtctcgCACACA +CTCTCGCTCTCTCTACACACGCGGCGCGCAAAGCGTGTGCGTTGCGTGCG +CGtttttttcactctctctgtgttctttttttctctgcgctctctcacac +tctctcactgtctcttctgcccaaaaaaaagttttctagaagaagaagag +gaatatATAAATTTGATTTATTGATACTTAATTAGAAAATGATAAaggca +gagagagagagagagagagggtgagagagtgtggggagatgagagagcgc +agagaaaatGAAGCCTACAGTAGGACCGAAagaaggggcggagcctaaac +tTTCCAAAGGAAATTGAGCAGAAGCAGAAAAAGCGAGGAGCCAAAATTAT +GGGTTGTTCtgtgtttgtatgtgtgtgtgtgtgtgtcaaaataggctccg +cccttTTTGTGGGGTACGGTAGAAAAATGCATGACCGGgatgacctagtt +tttctaGCTCCcggattctaggccactgtATCATTGCGACCTGGCCGtgg +gaattctaggccatcggcTTGTGGCCTAGGTTTTCGCCTGAGCAAAATTT +AGCTAGCTAAAGCTAGATCAGCTAAAAGGCGGTGGCCTAGTTTGGGATTC +TGGGCCAGCAGCAACTTTCACAGCCTCAAGACCATGGCataaaactaccg +tagtcGTCGTCTCGCTCCTCCAgcggagagaaagaagaaagtgagagatt +tagagaaaaatttagGTTAGAGGGAAAAATGTGTGCCTTCTTGGCTCCTT +CCTTTGCAAATGAGACCCCAGAAAATttccgagaagaagaagaaggaaaa +agggggcggggccaaaaaaaaagaacgacgGAGAGTGCAAAAAGGCACAG +AGGAAAGGAGGTTCATCTAGGGAAAGTGGGTCCcagactttcagattttc +aaattttcctaaaatccgaaaatcgcAAAAGTTGTGAAATTCCGCAGAGT +TTCCTAGGAATCCAGAatcttcaaattccaaaattcaggaTCCTAAAAAT +CCAGGATCCCCAGGTTCTAGAATGCTGGAAATCCTGAAACTCAAGGTTCT +AGAATCCAAGGATCTAGAGATCCAGAAtccaggttttcagaatttcagag +atcaaGAGTCCAAGAATCCAGGAAGCCGCAGTTCTAGGTTCCAGAATCTC +GAAAgcccagaaatccagaatctagaagctccgcccactaaACCCAAAAA +ATGGCCTCTTCTCGAAGACTTTCCTAGACCTAAGGCCTAAGACCTCCCAG +AACATCCTACCCGGGTGGTCCGGCCCACCCAGCACCAAAGGTCTAAAACC +CCAAACTGAACCAAGAATTCTAACTAAAAAAGacagagaagagaaaaatg +cgAGAGTACGTTCTGGGGCGCGGAGGGTGCGAGTGAATCAATAGAAGAAC +CCAGGACCGCCCCGGCGAACAACGAATGTGGCGAGTGATCATAtgagacg +aagagacgcagggaGGCGGGAGAGAGACGTAGTGGAGATGCGATGCGCCC +GTCCGCACCGACCGCTCGCCGCTCTCTCAGGTTTTCGTGTTGAATGGGAG +GAAGATTGgagaaaagggaagaagaagatgaagagggGCAGATGATATTG +GCTCCTGGAATCAGGTCAACCTGTCAGAATCTCTTCGAACGCCTTCTGCT +CTTGGAGACCTTCAGATTCTTTGGGTCTAGAACTCGGAGCAGTTTAGCCA +GCTCCAGCCTCTGATCTGGACATTTGAAGCTTCCTTGCCAGATTCTGACA +AGCTAGGAGAGAAACGCACGTCTTCTGATCTCCAGTCTGAGCTGAGATAA +GCAGGTCCCAGTAAAACAAACGATCTAGCTAGGTCTCAGAAGCAActgga +agcttctggaaacttGAGGAACGATCTTACGCCTTCCAGAACCATTTTGG +CTCATCTAGTCGCGTCCATTGACCATTTAAAGACAACCGAAACCTACTGT +AGAGTCCGTGCCAAGACTTCTGACAAGCTAGGAAAGCGTCGCATACCTTC +CTATCAGCTCTCAGAGTTCTGAGATCCAGATTTAGGCTTGGATAAGCCAT +TCTCTTGGTAAACTTGGTCATCGAATCATTTGGTAGCTTCTGGAAGATTT +TGGGAGCTCAAGACACCTTCCAGAACccattttgaccaatttcgGCTCGT +CTAGAAGACTATGGGCGAAATTAATGACAACAGAAACTTCTTGTAGATAT +ACAGTAGACCCAGAATTTACAGCTACGTCTAGAACCTTTAAATCCAGAGA +ATTGATCTTTCGCCTTCGTACACCATTCCTAGGTTCTCGATTTTCTGCCC +AAGTCGACAGTTCATCGATaacatcttcatttttttctccatgACGTCTT +CATACCGATCTCTACTTCTTACTTTACACAGCTACTGTCAtcctcgaaaa +aaaacgacttcTCGAAGAATtcttgagaagaagaaatattGTCGACAAAG +AtacctttttttctagaaaaaaaaatgagaaagcgAACTGGCTTGGAGGC +CCATATAAGACACTTTCTATATAGTGCCTTCAGGAAGTACATCTCCTAAA +CCATTAATCAATCGCGGGTGCCAGGTGCGCGACCTTTTCGGAGTGATTGA +AAGGCCAAGATCGGTGCATTCGACATTATTTACCTCTGGACCATAGATAT +CATCGTTGCAAACGGGCCGGCAGATAACTCGGCTTCAGAACAAGATGTTT +TGACGGATTTGATATCAAAAGATAGATCTCGACGGGAGNNAGNGAGTNCA +TCTATTCCAGGTGTAGGGCCGCCCGGAGAGGTGGAACCGTAGAGGTGGTT +GGAGCTAGATTTCTCATTCTCTTCTTCAAGGTTCGTACCTTGGGCACAGC +CgaaagtttttagattttccgactcccagaatctcaggaaGCTTTAGAAG +CCCAAATCCTTCTGAAGTTCCCTCAAAAACCCTAGTTTTAGATGAGTTTG +Gnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnaTGAAGTATTTTTGTAGAATTCCAAACTT +GACTTTATTCAAACCTGTCATAGTAGACTTCATAAGTGCCAtataagctt +aattatctcggtttccattaaagatatgaaaattttgtgaactgataaaa +tgttggtgataatgtGTTAAGCAGTTTATCAGtccccaattttttggttt +atttaagtggagctgagataatttgactcaaattcaaaagttaagGGACT +GTTATATTATAGATAGACCGGAATTTTTCCATATCTGCCATTCTAGACAG +GCCATAGGCATGTTAACGGACCAGAAACCGGCCCGTGTGGCATGTTAACG +GACCCGAAACCGGCCCGTGGGCTAAGATGGACCtcgtcgagatctatcat +ttgatAAAATATCTCGTTCTGAAGCCGAGTTATCCACAACTATCTCGAGT +TAGCCCGTTTGTAACTATGATAGTAATATCCTATGGTCAGGAAGGACCAT +CCCTTGGAGGATAAAAAGTCAGTTAAAGGCGCAGCGGCCAACAAACAGAG +ACCAGGCGCCTTTAAACgattttcggcgattttttcaatcagaattttga +gaaaaacatgGTTTTTAAAGGCACATGTTCTCAAGATCAGAATCGCAATA +TTAGTCTCATGGCATTTGAAATTCGGCATCGAGTCAAGTTCAGACGCGCC +GCGTGTCGGCGAGGCGGTCGCCAGATGAGCAGTTCAGCTCAACACCCCAT +TAAGATgctttaaacttcaaaatttcaggtttcctACCGGAATACACCTA +ACCTCAAACTGGGTAAAATTTGCCATGGCAATTACGGTCAACTTGAAGCG +GCCAAACGCCACGTGGCGTCTTCTGGGTCGGCCGAAAAGACTCGGAAACT +AcaagaattttcggaaactccGATGACCGTAGGCGTTGGTCTCGACACGA +AAGCGTTGAATTGAACTTTCGAATCTTACTGTTTtgtgaaaactcgaaaa +tttctaaaaaatccgagaattttcagaaaaaacggAGCAATTTCGAAcat +cgatctgaaaaattccaaaaatcgaaattcgaataagccggaaaaacgag +aaaaatgcGGCTCGTTCCATGCCACGTGGCAAGCGCCggctgaaattccg +aaaattaccgcatttttggctgaaattacAGTCCTGCTGATTTCCTGAAC +CTTCTGCTCTGAACCTAGTCGCCACGTGGCAAAATTTCCAGGCCCACCGC +CGTTCCAACAGGCGAATTTCAGTCAGACCGGAATTTCTGAGACTTCCGAT +GAGATTTTGACGGTTATCAaccatttttcgatgaaaaaacccaaaaattg +agtCGCCACGTGTCCCGGAAAAGGTCGGAAAAGGTGGGAAAATCGGAAAG +CCTGTAAGTATCCAGTGGTCCCGCCGAGCCatcggaaattggaaaaaagg +cTGTTCTTAAGGTCGGAAATAGGCGATTCAGAGCGATTTTGGCGGAGAAA +AAAGTCGAGATTGGATGGAAGATTTCATGGCAGCTGAAAATCTTGGTATG +CCAAACTCATCTAAAACTAGGGTTTTTGAGGGAACTTCAGAAGGATTTGG +GCTTCTAAAGCttcctgagattctgggagtcggaaaatctaaaaactttc +GGCTGTGCCCAAGGTACGAACCTTGAAGAAGAGAATGAGAAATCTAGCTC +CAACCACCTCTACGGTTCCACCTCTCCGGGCGGCCCTACACCTGGAATAG +ATGAACTCACTTACTCCAccaatccagaagacgttacGATTTCCAGAAGG +GGGCTTATCAGAAGGGGTGGGGaaagaagaatgagaagaCTATCCCATTC +TCCTAGATTCTTCGATGACATactcttcttcgttttctctAACACATAGG +AAgaagatagagagagagagacagaaagACACCACGACCGCCGCTACACA +CATTTCTCTAAATCTCATACACTCTTACACTATTTCCCAGCTGTCTATCT +CCTCTCTTGCTTCCATTCGGGTTGTtcttttctgcgtctctagccgcAGA +GCGCCAGAGTGTGGTGTAGAGAGTGTGGGAGAAAAGGAGGGCAGAGACGA +CGAGACAAAGataggagaagaaaaaggggcggagtctgaGGTGGAAAGGT +TTGCATGGTAcgagaaactgaaaatgggATGAAATTGGGATAATTGAGGG +ATCAGGGGGTATTCTGGAACAATTGAGAAGGACCAGAGGATCGGGAAACA +TCGGTGGActctttttttagatttccgaGACCCAGAAAGATTCCAAACTG +CTTCAACgtcgatttttccagacttttcTAGGTTTCTTCTGGATCTTTCA +CTGATTTCTACTGATTTCCATCGATTCTTATCAATTTCTCACGAAAATTC +TCGAGAAACCCAGCGAAAAAACTCCGAGAATCAAGTTCGCCGGAAATGAA +AACTTTATCCGATTTTTGTCGgggttttttggagaaattgaaattttagc +taGTTTCCAGCaatttcttcaactttttcgcTGAATTCTGACctagaatt +cttgaaaaagtgaggcgaaaactcgaatttcgaaGCCAGCGGCGGTGCTG +AGCAATGGCGACGGATTCAGATGAAATTCTAGGTTTTTCTAAGCGGTTAG +TcggtttttcagaacttctggtAATTTTAACtagaaaatattccgaaaaa +atcgaaagaatcAAAGAAAACCCAACAGTGACGTCATACATTGTGCAAGC +GAGCTTCTGAAGCTCGCCACGTGGATTCGGGGTGTTTTTTGGtggaaatt +tgtgaaaaccGAATActtctgttgattttcagaatagtttagcagaaaat +tcaagaaaatttggtGATAGAAATTTTAGCGAATTTCATCCAAATCGCTG +TCGCAAGTGCAGAAAAATTGGGCGATTTTTCTAGGGGGAGTATTCAGCGA +AAAATCCAGATAATCGACTCAATTATCAATGATTATATGTTTAAAAGTGA +CGAAACAACTGAAAATCCGAATGAAAATCTCGAAGCGGAGGGGGCGCGAA +AAAATCCAAGGAAGATCAATTTTGGCCAATTTGGTATGGAAAACGTCTAT +CGGAGTCAGAAAAAGAGacgaaaacaaagaaaattcatatgaatttcagc +aaaatcagcattttcagcaagAAACACCGGAGaaaatagtggaaaaaacg +agaaaaatggctcaaaaaccaTAGGAAAGCCGAGGAGTCGTCGCCACGTG +GATTACGGTTTTTCGGGAGAGATTCAGGcgaatttgttgattttcagcgt +ttttcgctgaaatttttcttaaatttcactTAAAAAACCACGAAATTCGT +CTGGATTAATGCATAAGCGCCATTTAAAGCAACAATTTtcgcaaaacaaa +aaaagaactatcggaattccaattttcgagtttttgaagcGTTTTTGACC +TACAAATTGGTAGAAGCAGAAAAGCATGAAAACTAGAAATACGGCTTAGT +TAAGCCTAAATTTACTCTCGTCCGCGAAATCGTGAGCGGGCCAGGCCGGC +CAGCCAAGCTTGGTGTCAAACGAAGCTTGGCGGCTACCGCATTGGAATTC +TGCAAAttcgaaaactggaaatttccaaaacttccagcaaaaaaaatcca +cagaatttaaaattcaaaggtCTCTGACAAGGGTCTCACCGCGAAAGCCA +ACTTTTTCGAAAGCTaattttcgtggtgagacctGTTGGATAGAGTTTCT +ACCGtagaagcttccagaagcTTCGATGCCTTTATTCGTCTCTCCGAGTT +CTTTCTCTTATCAAGTAGTATTTAGTGGTAGTAGTACAAAATAATAGATA +TTTCATCAagtcattcttcttcttcttctgtttactcttttttgttttct +ctgcgtctctcatcaCTAGGcgattctttcaaaaatctattcaGATACTG +GAcgatgaaaaaattaattaaagcTTCTGAAAAGTGCATAGAGTGGAAGC +TGGAAACGGCGAAAAGCGGGAGATTGATGAAAAAACAAGTGAAACAGAGG +GGAAGAATTCTCGGCGGAAACGATCCATTGGGATaaaatggatggaagca +aaaaagaaaagggcgggaaatttaaattctccaaaaaaattatgttttga +CACGATTTTTCCCGGGATTCCTGTATTACTCTAGTGctgtttttttgtaa +aaagttggctttcgtggtgagaccctTATCTGATACCTGTGAATTTAAAC +GACTTaattctttggatttttgccAGAATTTAGCGGAAATATCAAGTTTT +CGAATGTGCAGAATCCCAATGCGATAGCCGCCAAGCTTCATTTGACACCA +AGATTGGTGGCCAAGGATGGCCGGCCTGGCCCGCTCACGATTTCGCGGAC +GAGAGTAAATTTAGGCTTAACTAAGCCGTATTTCTAGTTTTCATGCTTTT +CTGCTTCTACCAATTTGTAGGTCAAAAAcgcttcaaaaactcaaaaattg +gaattccgatagttctttttttgttttgcggAAATTGTTTCTTTAAATGG +CGCTTATGCATTAACCAGACgaatttcttggtttttttaatgtgaaattt +cagtaaaatttcagcgaaaaacgctgaaaatcaacaaattcgCCTGAATC +TCTCCCGAAAAACCGTAATCCACGTGGCGACGACGCCTCGGCTTTCCTAT +GGTTTTTGAGCCGGTTTTTcttgctgaaaatgctgaatttgctgaaattc +atacaaattttctttgttttcgtCTCTTTTTCTGACTCCGATAGACGTTT +TCCATACCAAATTGGCCAAAATTGAtctttcttggattttttcgcGCCGT +CGCTTCGAGTTTTTtatccgaattttcagcgGTTTCgttacatttttgaa +gatattATCATTTATAATTGAGTcgattatttgaatttttcgctgaaTAC +TCCCCCTAAACGCGAGAAAAATCGCCCAATTTTTCTGCACTTGCGACAGC +GATTTGGCTGCTCACTTGCACGGCGAGTGACGTCACTGTCGGGTTTTCTT +AgattctttcgattttttcggaatttttccagTTAAAGTTTTAGGTCCTA +GTCTAATTTCAATGCGCATTGCGGTCGAGAATTCGGAATGagcggagctt +aggtccggtcgcgaaaactttaaattcgcatttaaaggagcatgtgtttt +ttttctatttcccgACATATTTGAtggattttgaactttttttgaggaCA +AAAATTCAGACAATCGCAAGAAATTgcataaaaacttttttcgacgaact +tttgaaattcgtcatgcatgcgcctttaaagctgTCGCTACGGTAAAATA +GCGAAAGTttgagttacagtaatcaattCTGCCTTGAAAAATCATGCGGA +CATTCCTAACCCATCATTAAATTTGCTCATTCGAAACCCCACCCGTCTAG +GAGCAGGTGCAGATGGAGGTTCTGAGCGGCACCGAGACACCAAAGAGGGG +GATCAAGTCTGGTTCATGAGCCAGCAATTAGTCAGGCTCGGAAGAAATGG +TTGACAAATTGAGGTGGGCGGGGGGACCATGTGAAAAGGTGTAAAAATTA +AAGaagactttgagctcagttatctcggttacagtaaccgagataattga +gattaaAATGGAAggtatcgatttttcaaaatttgtagtGTTAACAgtca +taaaaatgaaattcgtttaataaaaaaagaaaattcaaacaacgataaca +atgataacaaattcaacaaaaaatcagtaaaaatcctaGTCTTCATCATT +GAATAAAATGCGCTTTCCAGCTGGTTTCGCCGCCGCCAACTCCTTCTTTT +TGGCTTGAGAAGCGAGCCACGATGGATGCATTTGgccttctgaagacgtc +gaatTCTTCGATGTGcccttcttcttgttttcggTGGTAGTAGCTGGGGg +ttggaaatctggaaaattggggaatttaggtttgaaaaaatctgattact +tggaatcctaaaatttcaaagaaccAGAATTgtagaatctttgaatttca +ggatctcagaatttcagaattccggagtttcaaagattcagaaattcaga +atcttagaatttctgaatttctgaattccggagtttcagagattcagatt +ttcagaaattcgaaaattcagaaattcagaaactcagaattttagaaatt +cagaattctagaatctgagaatttcagaattctagaatcttggaatatta +gaatttcgaaaattcagaatttcagaaatttcagaattcggatGAATCCC +ATAATTCCCGAATCCCGGAGTTTCAGAGAATCAGAGATTCAgatcttcag +aaaattcagaaattcagaaacttagaatattaaaatttccgaatttcaga +acctagaattcagaatctcaattttcgggGAAATTAAGAATCccagcatt +tcagaatttcagaatctcccaattttcaaaactttcagaattcaaaattt +ctgaattttgggaaattttagaatccaatATGCTTCCAgaatacaaattt +cagaattctcaaaattccagaaatcaagGCTTCagaatccgaattttcag +atttctctgattttcagaattcagaatctttggaatttcaaaaattcgaa +ttccctcCAAAAAACGCACtcttctttcccactggtcccttcttcttcgt +attcttattcttcttcatcttcagaTCCTCCTCAACTCccaatttctcca +ttttcttcgCGATTCCTCCAGATTCCGGCACTGCTTTCGATTTAGAAGCT +GAAGACGTTCCTTTAGAGGACGCTGGAAGGAAGAATCCAGAGCTCtcgtc +ttcagaattctcctcctccacgtcttctgaagcctTCTTTGGAGCATGAG +CAGCCATCGTCGATTTCGGAGCCGCCGTCGATTTGGCTATTTTTCCACCT +TGTGATAGGTCGATTTTCATGACCAGAGTTTGCTGgaagaattagaaaat +ttctgaaagttctgaaaaaaaatcaaaattttgaaaaaaaaaatcgaaat +ttcgaaaaaatcaaaaattcaaaattttgcaaaaatcgaaattctgaaaa +attcaaattttttgaaaaatccgaaaaattcaaaatttcaagtctttgaa +aattaataattttcaaagtctgaaaaattcgaaaaatcgatattttgcaa +aattcaacattttttgactaaaaatgtttttttcaaaattttcttttcca +gaattttctggaattttcagacaaacctGATTTGGATCCTCTTCCTCCTC +GACGTcatctgcttcttcttccacgtcttcagaTTCTACTTCAGAAGACA +CTTCCACCTTCTTTGGAACCAtttttttCGGCTTTTCCACCTGCAAAAAT +GTCcaattttccaggattttcgTCCTCCGTCCATCTGTGTATCCAGATGT +CCTCTCTTCATACCTTTTCAGCCTTCAACGCCTTCTCCAACACTGCCTTC +ATCGCTTCTTTCGTTTTCTGCTTCTTCGATGGTTCAGATGACGTCGTCTC +CGTGACGTCTTGTGAATCGTCGTCAacgatttttcgcttttttggaTTGA +GAGCCGGACGGGACGCGTCTTCCTTGACACCGATTAGATTGAGGAgctgg +aaatttaaatttaagaatctgtgaacttcagaatcccagaaattcaaatt +ttcagattttcataacttcagaatcctagaatctgaacatcccaaaatct +caaaatttcgaaatttcagaatcctagaatcccagattttcggattttca +gaaattcggaatccctgaatcctggaatctcaaaatctcagaatcctttt +tttttttgaaaaatccgaaaaattcaaaatttcaagtctttgaaaataaa +taattttcaaagtctgaatcccagaatttcagaagccTCAGGAGTTCaga +atcttaaattttcagaatctaagaatctaagaattgcagatttctgaact +tcaggGTCTCAAGGACTTCAGGATCCTGGCGttccagattctcagaattt +cggaattcaagaatttcaaattttcagaattccatgAATCTAGAATGCCA +GAATCGTAGAATCCtgacatttcagaatctgagaattccagaatctgtga +atttcagaatcccagaaactcagattttcagattctcggaatttcgaaat +ttcagaattctagaatacTGGAATCTGAGAATCGTAGAATCTGCGAATTC +AAGGATTTCaggttttccgaatttccgaaattcagaatctaagaattcta +gaatctcagaatcgattttagaatttcggaatactagaacttcagaatcc +cagaatttcgaaatttcagaatcctagagCTCTAGAATCCTGGAATCTTA +GAGtatcagatttccagaatcctccaaattcagaagttcagatttCCAAA +GTTTCCGAACTCCAGattctcaatatttcagattttgagaatctcggaat +ttcaaaaatccagaatctgagaatccgaGAATCGTAAgaactgaaaatct +caaaacttcaaaatttcagaaatgcagaatcttagaatctgaaactttca +gaatcccagaatctcaaaatccccTTCTCACCAtatttctcctcttcttc +gcCGCCTCCACCCCGACGTCTTCATCATCACTATCCACCATTTCGACGTC +CGACTGATCGTAGTCATCTGGAGCGTCCtccccctcttcttcttcttttt +ccacgtcttctgaatcatcCAACGCATCTTCCTCCACATCGCtctcttct +ccagaatccACGACGTTTTCTGAATCCGTTTTCGCCTTCTGAATTCCCTT +CGTTTCATCAGAATGCTTcgcttttttctcctttttctctggTTTCGTGG +AGTATTGCCTTCCGAGCCGTTGCATGAAAAACGCCGCCGTCTTGTTCCAT +TCGATAtacttttgtctgaaaatttcagaattttcagtcatttttcagct +attttcagccattttcagttattttccgctattctgttttttttcagcca +aaaaaaacctcgaattttcggattttggattattttcagtcaattttcag +ccgattttcagctattttcagccattttcagtcaatttttagccggtttt +tagcttcaaatagccagaaaaccctaaaaattccctaaaaattgaatttt +cagctttgaaaatgtcatttttcaagccatttttcaccaatttttcagtt +accaatttttccaatttttcagccgaaaatgtcgaatttttgaatttttc +agccaattgtTAGCCGATTTTCAGTTACTTTCAACCAATTCTCAGGCAAA +AAAcgccgaatttttgtatttttctgacaattttcagatatatttccagc +caattttcaacttcaaataGCTTTTTTGAGACACTataaattggattttt +agcttcgaaaatgtcatttttcagactttttttcagccaaaaaacgtcga +attttcgaatttttgcatttcggatgattttcagccaatctcagctattt +tcagcatttgcagtcattctgaacctattttcagccaattttcagttatt +ttcagctattttaagtccaatttcagccgtttttcaaccaaaaatgtcga +atttttgaatttttcagcctattttcagccatttttcagcgattttcagc +caatttttatctattttcagctattttcagccaattttctcccatttttc +agccaaaaaaactttaaagtttTACTTGATCGCCTGAATTCTGGAAACGA +CGACTTCATGGCACGCCAACTTGTACATGACTTGCTCGGCCATCGGCGTG +GATCCAtcgattttcagttcattCAACGTTTTGGTGTTCAGCGAAGCGAA +TTTGGCGATGGTGTCCCGATCgattgtctggaaaaaaaatttcagtgaaa +attttcgaaattctcgaattttctagatttttctatgGCTAAAAACCCCG +ATTTTCTAGTTAATTTTAGtgagaaaaaactgatttttcggtgattttca +ggggttttaactttaaaatttggatttttcgcctttttttggctgaaaat +ctcagcattttttcagaaaatttttggggtccaaaaaactttttggagcT +CAAAGAAGgctaaaaatcgctgaaatgcctgctggaaaaattcgaaaatt +cgaaaaaaaaatgttgtttcaaACCAAACTTTCAGccagaaaaatcgaag +ttttagagccaaaaatccaatttctagagtcatttttaagccatttttag +cgattttcagcgattttcagctatttttagtgaatttttagtcaatttcc +gcttattttcaactattttcttacaatttccatttttcagctactttcag +ccttttattcagccaattttagccaattttcagctatttccagccatttt +tcagttattttccactattttcggccaatttcccgctaatttacagccat +tttttcagccaattttagccaatttacagtcgttattcccgctttcattt +tcagccattttcagcgattttcaagacattttcaagccgattttcaagcc +aatttcagctactttcagccttttattcagccaattttagccaatttcca +gctattttcagttatttttcagttattttcagctattttcagcccttatt +tcgatttttaaccCCCAAAAATGCTTTAATTTCTCACCTTTAACGCCAAA +ATCTCCTCCATCATCCTGTTCAATTTCGCAtccaccacctcctcttttcc +accttttccctcctttctcttcttttccaattcctttttcttcctgATCA +CTTTGCTGATCCATTGATCTTTAGCCTTCGTTACCGTCGCGCGAAGTCCC +ACCAGCtcattgttcaatttttctgctGTGAGCTGGATTCGGCCAGTTTC +AGCatctttttcagccaatttttgagcttctggagcctttttcgcttctt +ttctgagtgatttttgagcattttccgGTCTTCTAGCGTCTGAACCTTCC +TCCCCTTCAGAatccgatttttgagcttctggagcaattttcactgattt +tttcggttttttcatcgattttcgatcattttcagccttttccatggttt +ttggcgcatttttcGCTACCAAATTCGGCAACTCGAATTCGATGACCGGC +GCGGCGATGTTGGACATATCGAACACTTCATAGTcctctgccacgtcatc +agcatCGTCGATTTGGGCCATTGGCATTTCGATCGAGGCAGAATCGTCGA +TTTTCTTGACTTTTTTGACCATCTGAAGCTTATTTTCgtaaaaaatgggg +aaaatggaaaagaaacggaaatttgccccaaaagtaggaggaaaactgaa +gaaattcaatgaaaaatatgtcgaaaaaccggaaaatttgcaccgaaaaa +tggaattgaattttttggaaaaattggcgaaaagtgaaatttcggagaaa +tttCGCCCAGTGAAATCTATGAGAATTATGTTgaaaacccggaaatttcg +ctcaaaaaatagggaaaaaatatcaaaatttggaaaaaaaatttagttgt +TTTGGATCATAAAAccctttgaaaaatcgataaaagcacaaatttttaca +aaagttttctaacacattcgatttttctcacttttccttcaatttttgtt +ctttttcgtgtagaaaaacatcaaaaatctcaattttctacccgtggcct +agaaaacagaGGAACTTTGGgaaaaagctaggccaccggcgaaattcgaa +ttttctgcctcattttttggtcatttttcatccaaaaatgcgtttttcgt +gctcaaaatcgagaattttgggattttttttgtaattagtcaattttaaa +tagaaaaatcaaagaaattttcgagatttttcagaccaattttcgaaaaa +tttcctgaaaaacctaaaaaatcagaaagcaATAATTTATATATAAATAT +CGTATAAGCTCAGCGATattctatatatttttcaactgGGAAAATGGAGG +GGATGGGCGGAggggcaaatttttgaaaatttacaaaaattaaaaattta +ggaaaaattcagaaaattgaggggaaattaagcaccaaattgataaacaa +acaaagaaaaagcgggcaaaaattcagaattttcaaattttcaaaaatta +gaaaattagaaaaaaaatcacgggaTTCTGGAGGGAAAAAAGTAGGTGTG +GCGCTGGGAAGTTTTAAGAAATTCTAGAGAGAATTATcacatttttctgt +tgatttcgGGATGAAACAAAGGCACTTAACTGGGAATAATTATGGTATAT +AAATTagggaaaaatcaataaaaatgaatattgGAAGGATAGgagaagaa +tacaaaaatgtacaaaatttgagagagaaaaaagggcattttaagagaaa +tttgagcgcagattgctcagctttaattAAAGTGGCGGCTGGAACGAGTC +GCCGGCCGCGTCGTGATGCATTGGCGGTGGTTGATTGCTCATTGGTGGCG +GGTTGAACATTCCTTCGGTCAGATAACCAGCGACTCCCGTTGGGGCGCCT +GGAAATAGTgatttttggttgaaattccaggtttttagattatgtttttt +ttcttcgaatttcagatattcagaatctcagaaatcgTAGAAAATTCAAC +TAACCAGTAACCGCCAGCGTCCTCGCCGCGGGCAAGAACAAATCGTGTCG +TTGATCCTTGAATTGTGCCCAAATGGGGCTCTTCTCAAGTATCTCCTGAA +TCTTCGTTCCCACTTTCAAATCCAAAATCGCACTTTTCAGTGCATCAACT +ATCTCGGCACGGGCGGCTGCGCCATTCGAGACGCCATTCATCGAACTGTC +CAGCACCTCCAAAAGGTACGGTACCATTCCACAATTGAGCATTTGTTGAG +CCAATTCCCCAGTGTTTCGCTTCATTAGACACTTCAACGCGTGCGCGGAT +TCTCGCATCAACGACGGCtgatttttcatcgatttcatGATTCCGTCGAT +GCAGGGCAGTTGGGACAGGGCGTCACAACAGAACTGGTCTCGCTGAGCtc +ctggaaaaatgacaatttttttgaaaatttccattttttggagaattcgc +TGAAACACTAAACTCATAGATTTCAAGCCATAATTTGTTACTTTGggcca +gattttttttgaaatttcgaagcaaattttaatttttaaccagtttccag +ctattttcagccatatataagctattttcagctattttcagctaattgtt +agctattctcagctaattttaaccattttcagtcttttttaatttatttt +cagccaatttttagtcattttcaggcagtttccaactatttcagccattt +ttagccaatttccagccatttaagccaattttcggctaagatttagctat +tttcagcctatttcgatctattttcagccaattttcagccaatgttcagt +caattttcagctgctttccgccaatttcagtcgtatttcagcctaattag +agccattttcagccaatttttagcttttttcagCCGATATCCAGCTTCAA +ATAGACTTTTTGAGACtctaaaattggattttttagcttttcttTGCCCA +TTTTCTGTCGAAAATGCCGtttttttgtcagacaattctgattttctcgt +tttttaaattttttcatcttttctagaccataaacatgaatttttagctt +taaaaattgcattttccagctattttcaatcattttgagccaattttcag +ttatttttagctaatttccagccaattttaagctattttcagccaatttt +cagttattttcaactattttcagccaatttcccgctcattttcagctaat +tcaagccaatttcgagccattttcaagccaattttcagttattttcagcc +attttcaagccaattttaagccagatttcagccaattgtcagccaaattt +ttgtattttcagacaatctcaagccatttttttttcaaatttaaggcTAA +AAAGCCTCACCTGAAGGATCAAAATGGCCACTTTGGACGCTTCTGGCTTC +TGACTGCCCATATTCGTACAGAACTGTGGCAGATATCCTTGAGCCGGTAG +CTGATCAGCAGTGTTCGGATGATTACGGACCAGTGCCACGAAAGGCGGTG +GTGACCATTTCGATTTGAGGTGGCGGGCGGGCCATTAGTTCGAGGAccct +ggaaaaatgggaattgggTTATTGGTTAGGAaatggcgggaaattcgaat +tttaaattttcaatttttagaatttaaaggaattttaaaggtaattaGGG +CGCTAATTAgagaatctcaatttttcagaatctcacaatccCAGTATAGA +ATTTCGGATTCCAAAGGAAATTAGGTACTGAGAacctcagaattccagaa +tctgtggatttcaaaatcataGAGCTACAgtatttcggattttcagaatc +acggAATCTAAGAAGCCTACTAATCTTAGAAtcctcgaatttcaaaattt +ctgaattccagagtcagaaaacctcagaatctcagaatttccagactcag +aatctcagaatttccagaaggagaatctcagaatttccagaatttcagat +attcgtaatctcatttttcagaatctcagaatcccagaataccagattct +cagaatctcagaatttcagaatctcagaataccagaacaccagattctca +gaatctcagaataccagaatttcagaatctcagtttttcaaaatttcaaa +attcgtgaatttcagaatcttaaaaatttcaggttttcagatttttagat +tttcatgatcgagaatcttagaattccagtttctcagaattccgtaaatt +cagattctcagaatctcgaaatttcagaatttaagaatttcagtacacca +gattgtcagaattccagtttctcagaatcttagaatttcagaatccctga +atttcaaattttcaaaaagtttgattttcagaatctcagaatttcagaat +ctgcgagtttcagaagttctaaacctcaaaaattcaaattctcagaatct +caatactccagaaatccagaattccagaattccataTATTCAGATTcttt +gaatctaaaaattccagaatttccgaattccagaGACacgaaatttaaga +atctgcGAATCTCGgaacttccaaatttcagattcccagaatttcaaaac +tccagaatttcagaataccagattctcaaaattccagattcgcagaatct +caaaatttaggaatcccataatttcagaatttcagattctcagaatatca +gaatcttcgaatttcaaaatttctgatttccctCTCAAACTCACTTCTCA +ATCAACTCCCTGGCAAACTCCTTGGGATGTCTGACAGGCCATCCGGGATT +CTCGACAAACAGCCGAATGAAGACGCCTCCAACGACGAGTTCTCCACTGA +TACTATCACCATAAGCACAGTAATCGTCTGATAACGTTGTGGTATTCCAT +TTGGCCGTCGGGTCCTTGATATGCTTCTGATACAGCGTTTCCACCTCTTT +ATCAATGatttctttcacttttttccggGTGTTTTCGTTCCAAATCAACT +CGGGATGCTCGTTTGATGAATCGAACATTTGTAGTCTACAAAAGGTTGGA +CTACGGTCATTCAGatttggctccgcccatttttgaaaaactattgCTAG +TTTCCGTAGCTTTTGTCTCATGCTTCCCAGAAAATTCAGttccaaagtgg +gcggagctacaGACCTTCAGtacatttttaagtttctcatcaaaatgggc +ggggcCTAATATACCTTTGCTCCGCCCCTTTCCATTTTAGATGTCATTTC +GAGCtcctcccaaaaaattttaaaagtgggcggagctacaGATCCTTAAT +ctgttttttcatgaaaatgggcggagcttgaaaTTTCTATGAGCATTAAT +GACTTATATTTGCCgattgttttgattttcagaattttaagctccgccca +ctttcgaCAGCAATAGCTGTTAAAAATTTGGtcgaaaagtgggcggggct +agATATACTTATAttacaaatttcagtttttcatgaaaatgggcggagcc +aatttcagaattttttagaaattgggttcaaaagtgggcggagctgaAGA +TCCTtagtatattttttttccgatttttcgtgAAAATGGGAGGAGCCTGA +AATACGgaagcaaaaaatgaaagaaaattcgttcaaaagtgggcggagcc +tgtcACCTAATCGagatttttcaatcttttgaaaaatgtgggcggagcct +aaaatccgaagttttagatttttctaaaagtgggcggagtctgaaCCCTA +ATCGAGAAATTTTGATCTcttgaaaaagtgggcggagcctaaaatccgaa +tttcggattggtctaaaagtgggcggagcttgaaatccgaaattttggat +ttgtcTAAACGTGGTCGGAGcttaaaatccgaaattttggatttgtcTAA +ACGTGGTAGGAGCTTAGGATCACTAGCACTAGCACTAAATTTCACCCAAA +TATTTAGGACCAAAATTAAActgtttcgatttttctcaaaagtgggcgga +gcctaaaaacCAACTCACGCTGTATTCGGCGAGTCCCTCAACGCATCAGC +AAAGATCGCCGGCAGGAATTTGTTGATAAATCGTGTCCACCGTGGTCCCG +TCAGCTTATCAGCCTGCAGTTTCGCCAGAAGCTCCGCCGATTGAAGACGT +TGTCCCTGATCGGAATTCGTGAGGCAGAGGATGGATAGAATGTACATCAG +CCCTCCGTGCTCTAGCATCTCCTTGACTATTTGACCGTTCGAAGAGAGAG +CGATAAGGACATCCAGGACGCGGGCAACGATTTTAGGATGGTCTTTGAGC +AGTGTGAAGAGGGTCGTTGTGATATTACACGTGGCAAGATCAGTGACACA +CTCCTTATTGGCTGCGGCGAGGAGGATGACTTGGAGAGCGGCGATTTGAA +GTTGAGGGTGTTTTCGGCCGCGGAGATAGGTGATGAGCAATGGGAAGTTG +CCGATGAGCAGGATTTCGACGCCTGGAATATGCAtattattgctcatttt +ttgggcattttggCCATAAGGTCTGATAAGGGGGAGGAGAGAAGCATGTG +GAAAGGTTTGGGGGTGTTTTTAAGTGGAAATTCGAAGCTAAACGAAGGAA +TCGGGGGTCAAGACAGTCAAGGAATCAGGcgcaaaaactacaaatttttt +gatagattcACCAAAAACCTTACAACATTTATTCTCACCCTTATTGTTGG +CAAATACGGCACCTGGAATGGTATTCTTGTAATTTTGATAATTAGAACAG +TACCTTAGCGTCTGTACTAGAAGGCggccccctctaatagaaggacccca +tCGAAAAGATCATGAAGAAATAAGAGGACCCTCTTCAATAGTTTAAGCAT +CTACGACATATCAGAACTGTCtcattttagaactgtgacatttcaaaact +gtgacatttcagaactgtgaTATCTTAGAACTGActttttagaactgcga +catatcagaactgcgacatttcagaactgtgacattttagaactgcgaca +tttcagaactgtgacatattagaactgcgacacttcaaaactgtgacatt +tcagaactataacatttttaaactgtgacgtttcagaactgtgaTATCTT +AGAACTGActttttagaactgcgacatatcagaactgcgacattttagaa +ctgtgacatttcaaaactgtgacatttcagaactatgacattttttaact +gtgacatttcagaactgtgaTATCTTAGAACtatgacattttagaactgc +gacatttcagaactgtgacatttcaaaattgtgacatttttaaactgtga +cattttagaactgactttttagaactgcgacatatCAGAACTGCgatatt +tcagaactttgacatattagaactgcgacatttcaaAACTATGATATTct +agaactgtgacattttagaactatcacatttcaaaactgcgacatttcag +aactctgacattttagaactgcgacatttcagaactgagACATTTTAGTA +GGGCGCTCTAAAGGTCCCGcccttctgatacaggttttacggtatatttg +gCTCAATTTCAGACGGTTTTCAGCCATCCCATGCTCACCAGGATTCGCGG +AAACCAGATTCGACAACGCTGTCATCACCATCAACACCTTGGTCTCTGTG +TTCAATGTGTTTCCATTCTCCTGTGATGACGATGGTCCATTTCCCCAATC +GATTTCAATCAAATCGTCTGGATTCTTTTTGATTGGCTTCGGCACACCGT +TCAGCTCATCCGAGCTCTTTCGGATATAGTCCAACAGATCGACGGCCACT +TTTTTCGGTTCCTGGAAAATTCGGGGTGAAAATCGTAGTTTTGGAGTCGT +TTGGGCTCAAAAATCTAGTATTTTCGAGCCGAATTTCGCAAATTTCGCCT +CTGAAACgtgattttgagctcaaaatcgagatttttgggtacaaaaatcg +tcaaaattaGGCAAAAATCCACCTTTTGGGGttttttcttgcaatttttt +gcagatttcgcctctgaaaatcgtaattttgagctcaaaaatcgagattt +tcagcttcaaataAGTAAAAATTAGGGGCCAGAAATGATGTTATGTTGtt +ctaaatcaaaatttgggtGTTTTCCAGCCATATTTCGCAAATTTCTCCAC +GAAAGCTCGAGATTTCGAGCTCAAAATCTAGagttttggcttaaaattca +tcaaaattagACAAAAATCCAACTTTTGGGGTTTTTCCTACAATATTTTG +CAAATTTCGCCtctgaaaatcgcaattttgagctcaaaatcgagattttt +ggattcaaatcAGTCCAAATTAGGCAAAAATCCAACTTTTGGGGGTTTTC +ctgtaattttttgcaaatttagcctctgaaaatcgtgattttgagcttca +aattcgtcaaaatccgggcaaatttttgaagtttccggATCTGAATTGAT +CAGAAATAGGGGtcaaaattcaatgtttcGTTCAAAATCGACTCACATGA +AGCGCAAACGTCGGCTGCTCGTTGTATATCCGAATGAAGACGTCGCCAAC +AATCAGCTCGTTCTTGTGCACGGACAACTCGAACTCCGCTCCCATCAGTG +TGCTCTGAAGCGGAATTTGAGATGAGCAATAGGTCAGAAATAGccaattt +tgttcaaaaatgctcaaactTTGTGCGGCTCAAATTAAgccgaaaattct +aattttccagtctaaatttcaagatattttagtctgaattttaaaatttt +aagttgagcaatgagtcaaaaatcggctcggctcaaaattcgagaaaaaa +tgcattttccaAACTCTAAACACCTACCGATGGCTCATTCGACGTTCGAT +GTTTCTCCACAAACTCCAGCACCTCAGCTCTCGTCCCGTTATCCCAAATC +ATATACGGATTCTCCAGATTACTATTCAACGTCTTCAGCACCATATCGTT +CGTCTCCACACGCATACATCTACAGATATATGGTGTGAGCAACGCGCGAA +GGCTCTTCTGGACGCCTTCATTATCCGGCGTGTTCTCACGATAGCCGGCG +AGTGCCGCAAGGGCTTCGGAGGAGGACCGAGCCAGGGAATTCGCCAGCGA +TTGCTTGTTGGAGTCTTCTGAATGCTGAACGCCGCCTTCGTCGAGGGTGT +AGTCGTAGTGGAAGAGGTGGGGGACTAGTTGCCAGAGAACGCCAGTTTGG +AATAGTTGGAATTGGAGGAGCTCGTCGACGGACATTGCACAAATGCATTG +GGCAGCGGCTGTGGACAGGCGGGGGAGGTGctggaaattcaagattttca +gacctAAATTTTAAGATATAGGATTCTGGGGCCTGTAATTTACAGGCtgt +aaattccagaatccgGGCCAGAAATCGTGTAATTTTAggttcaaaattga +agttttcagcATCAGAAACTTCCCATTTTTACAGtcaaaaatctataatt +ttcagggcaaattttggaattttagaccGATTTCCGGGCCCAAtgcagac +attttttgaagctgaaaatcgataattttcagaccaaaaattgcaatttt +taagcggaattttaaagccaaaaatctATAACTTTCAGAactaattttct +cgatttttcagggttttttttcatgaaaaatctataattttcagaactaa +ttttcgacatttttagacaggatttttttcgatttttcagggtttttttt +cacgaaaaatctataattttcagaccagaatttggaatttttagacggta +ttttcttggttttaaaagccaaaatttcgtatttttcaaatcgaaaaaaa +tgctCACCGAGAACTGCAAAAGTCTTGTGAGTGCACCGAAAATCGAAACC +ATCTCAGCCAACTTCTGTCGACACATCTCGAATGTTGACGCCGTCGCGAA +GCAGTCGCAAACGTGGATACAAACTTGGACAGGCATGTCGTCTGGCGTCG +AACTCATCGTCACCATAGGGACGCAACGATCGAATGCGGTGACCAGGGCC +TGTGGAAATTAgagatttgagatttttaactATTCCTGACTAtttttttG +GGTGTTCGAGATTACTGCACAACCTGCATTAGAAGGCGCTTtcattgttc +caaggtacctctgGAGtgagagcccttctaatacatgctttacggtattt +ccattttagccgatttttagccgtttatgacgagattttttggattattt +tcagatttatttcaggccaattttaggcgttttgaggctatttcagtttg +attttttgagtagaAATTCATGcgtttatcatttttcagcatcGAAAGGC +TAAATTTCTCGAATATTAGCTATTCCAAATTTCCTCTCCTaagattttct +aggtcaaataCCTCCAATCCACCATCTCGTCTCAATTGCTCGGCATTCAG +TGCACTGCTAATCAGTGTGTAGTTGGCCAACTCGATCGCAGCTGACAGCA +AATCTCCGCCTCCTTTGATGAACAACGCGTCGTCCTTGGCCTCCAGGTTG +ATGGTTTTGATGAGTTGCGAGTAGCCGGCGTACTTGTATTCAGAGAGTTC +TGGaaattgggttactgtaggccaGATATTAGCCaatttcggtcaatttt +tAGGGGCatcattcaaaagtttcatccTATTTCCTCAGAAAacctcaaat +ttcaatttttcagctcacagctcagaaagcaaaaaatgaaaaacctgTTC +GAACCCGGATCGTGAGATTGGTAATAATGCATCGCACAGAGCCATTTGAG +CAgatggctcaaaaatggtcgaaattcggttttttttttggaaattagtC +ACTatatggttactgtagactatTTTTGGCCCCGCAGAGCTCTATTTTGG +GCTCCTACCTTGACTATACCGACTGTATATGATGGACTGTGCTTGTAGAC +ACAACACAATCCTATGCGAATCAGGCATCGTCGAGTTGTTGGCACTCTCA +CTGCTGAGCAATTCATAAGCCGCATTGATCCTCTCGAACATCTCTCTGCC +CTCTGGATTCTTATCCGGATGGTATTTGGCAGCCAGCTTGTAGTACTGAC +GACGTATGAATGCCGGTTTCCGATGCTCCTCATTGCTCAGATCCACTGAT +AGAATCTCGCGTGCCAAGTCGGCAGACATCGTCGATGGCTTCTTCTCCAA +CTCGTTGTACCATGTAGCCAGACAGGAGCGGAGGAAAGGGATCGGATCTC +GAATCGGCCAATCTGGGAACCTCTGTCGATTACACAGATGCCTCAAATAG +TAGACGTGACAGAAGAGCTCCTGAGTCAATTCTGGATAATCAATCAGTGG +AATCGGACAGAATTGATACAACGCTCGGACGTTGGAAGTGAGTCGATGTG +AGAAATCTGCCACGTGCACAGCGATCCTCTCAATCAGATGACGTCGCATC +GCAGTGTTCCAAATGATTTCCGGATTATCAAACTCTCCGAGGAACACCTC +CGCATACTTCTCCGGTCCATACTGCTCCAAATAGAACGTGGCGGCTTCGG +GAAGCAACGTGGCGAGAATCGATTGTCGTGTGCTCTCCAGATGAGGTAAC +GTCGAGCGATAGGCCTGCTTCATGTGGGTGTAATGAAGGAAACGGGCGAT +CGGGAGCACGTTGGATCCATTGTACATTAGAATGAAATAGAAGACTCCAG +AGAGGTAGAGACGGGGGAGGAATGGGTTGTCTTGCATGACTAGGTAGAGC +AGGGAAGCCACTCTTTGAACGATTTGAGGTTCGTAGGTGAGAAGAAGTTG +GACGAGTTGGTAGAGGAGGACGGGCTCCGTGAGCTGCTTCTTGACGGATG +GCATCGGGCGGACGACACAGTCGTACGAGTCCCTGGAACGATATGGAATT +GTAAGATTCAAAgattaaggatctaaggatatacggatctagggatctag +ggatctagggatctaaggatctaaggatctaagaatcggaggatcaaagg +atcggaggattttcagagctaatgatctagagatttaaggattgatctag +ggttcaaagaatctgaggatctagggatctggagatctagggatctatga +atctgaagatctgaagatctagggatctaatgatctagggatctaatgat +ctagggatctggggatctgggaatctgggaatctggggatctaGGCCGAC +ATATCAAAATGAACTAGAAATGACCAAATATTCGCCTAGTGTGCCTAGCC +GAGAAATCCCgagttgagaaagttaggccaccatgttgatATGGCTTAGA +AATGGTCTAATATTCATCTAGTgtgtttctaggtcatttcaacatggtgg +cctagaaaactcatgttgagaaagttaggccatcatgctaaaatggccta +gaattggTCTACATTTCCCCTAGTGGGTTATCTAGGTCATTTCaacttga +tggcctagaaaacccaagtTAGGCCattatgtcatttttcaaacagttgt +ctctgaaaaatttgaaattcaaggaTCTAAAGGATCTAAGAATTCAGGGA +TCTAGGGGTCTATTCGAGAATCCATAATCCTAGGGcttcagaatctccag +aatcttGAATTCAAGAATCTAAGGATTTgaggattctggaaatctaggat +tctgagattcgagAAGCCAGAATCCTTGGTCTTCAGAATCTCCATTCTCA +CCTCGATGGAAAGAACTCGCACATCTGCAGAATCGTATCCAAACAAAGCA +CACTCAAATCCGTGAAATTCATCTGTGTCGCTTGGAATGGTCCCTTCCCA +ACGTTGATCTCCTGCGGGATGTCTTTTGCCATCTGACACACCGTCCATCG +GAACTGTGGCACCGCCGCGAGACTCATCCATTTATCCATTCCAGCTGCCC +AGATCTGGGTCTTCTCAAACACCGTCTTCTCCACGAACAACGTCTTCATC +TTCTCAAATGACAATGGTCCCACTTGTTTAGCCTCCTTATCATGATAATA +CCACTCCTCGGATCCTCCTTCAGCCATTTGCTCAGCGCTCGCCTCGATCA +CATTCGTctgattttgaactttggcTCTTTGAACGTGCAAGTGTGCTAAA +ACGCATAAATCCACTAGGAGGGGCAGGACATTGGCAATGATCAGCTCTCG +AACGTTATCCTTGTTTAGAGCCAACTTGGAGAGCAGCAGGACTAGATGGT +CTCGTTCCAAGGGGTTGGCGCATTTTTGGAGCATCTCCACGAAATATTTG +GCGTCCTGGAATGGTCCGATTGTCATGTGATGGCGGGAATAGGTGATGGA +CATCGCACGAAGGCACAGGCACTTCATATCGGTTTTTGTGGAGAGCAGGA +AGCGGTGATAGACGTTGTTGAAGAATTCCAGGCTGGAAATGATAGGAGAA +TTGGGGATTTTTCGGAGAAAATTCtagcattttcagatttaagtCTCTGG +AAAGAGTTGGAATTGTTGGGGTTAAGGATCTAAAAATCTGACGATTCTGG +AACTCCTGGATCTCGAGAATTGCGAATCCATCTCCAAACCtctgggatct +gggatctaaggatctacggatctacggatctacggatctacggatctagg +gatctacggatctacggatctacggatctagggatctagggatctaggga +tctagggatctagggatctatggttctatggatctagggatctaaggatc +tagagatctagggatatagggatctagagatctacggatctagcgatcCA +GACATTCGAGAACCTAGAATTTTGGGAATCCAGAATATGAAGACTCCAGG +ATCCAAGGATTCAAAGATCGGAGGATCGGAGGAAACAAGAATCCTGCGAT +CTACAGATTCAAAGATCccgaaaaaagctgaaaatttcaaaatatggaTC +AAATCATACaatttctggctgaaaatacgcactattttcagccgaaattc +actattttcacagtcgaaaattcataatttttttgtctcaatTTGACAAA +TTCTAGATCGAAActcatgattttcagatctaCATGTGGAATTTTCCGCG +CTAAAAATTCACTATTTTTAGAGTCGATTCTGAgtcgaaaattcataatt +ttgggTCTGAACTCCTGATTTTTCTGGTCAAAATTAATGATTTTCCGATC +GAAATGTGGGATTTTCAGCGCCGAAATTCgctatttttaggctgaaaact +CATAATTTTCGGTCTTAATTTCACGAATTCGAGATCGAAActcatgattt +tcagatcaaaatttggctttttGAGCGCCGTCATGTTAAGCCGAAATTCG +CTATTTTCGGGACTGAAAACCGTCATTTTCAGTCCAAAAAGTGTTTAAAA +CGGTGAAAATTCGcacttttttcagccaaaattcaCCATttttaaagtcg +aaaaaaactcatatttttgggtctcaatttcacaaattcgagatcgattt +tatgattttcagagcgaactttggaattttcagcgccaaaaagtgttttt +gaaaagGTGAAAATTCGCACTGTTTCCAGCCAAAATTGACTATTTCTAGG +TTGAAAAATCATAGTTTTTAGTCTTAATTTCACAAATCAAGATCGGAATT +CCTGACTGTTCAGGTCGAAATTAGGCATTTTCAGCGCCACAAatgccatt +ttcagacaaaattcacaattttaaagtcgaaaattcaataattttggttc +ttaattcctgatttttcagatcaaaatttcaaattttcagggccaGAAAA +CTGTCAATTTTTATCCTGGTTTTAAGTATTTTCTGGATGAAAAttagcca +ttttttctcaGCTAAAATCATTAGTTGCAGCTTTTTAGGACTAAAAACTC +ACGGATTATGAATAGGTGTCGCATTCTCATCGGCCTCAATCAACAACAGT +CTCAAGTAGTAGTCTCCAATCTTAATCTCCTCCAACAGCGAAGGATATCG +AATCTGGAATTCCGTATGATTCCAAGCGATCGGCAGTCCAGTAGGCGCTT +GTTCCTTCTCACTAGCCAGAGTTCGCTCCTCGTTCTCCATCGAATGCCTA +AACTCCTCTCGCGTCTTCTCATTCCAAATCAGATCCGCCTGCGAGTGATC +TTTCGAGAACTGATAAGCGAAAAGCCTCCAATTAACATTAGGGCGCACTC +GATTCCTTCGTTTCCGAAGGACCACCGGTTGCTGTCGTTGTTGTTGCTTC +TCGTCGATAACTCGTTTCGGTAGGAAGTTCAGCTTCTGCTCCAGATCCCA +GTGCTGCACAATCTCTCGAATCCCGCCTCCGCTGTCACTCTCAGGTGATC +CAGTTTCTCTTTAACCGTGTTCTGCTTCGATTCATTGGTAGCGGCACTCA +AGTTGTTCCTGGGGATCAGCAGATCCTTCTCACTAATCGGCACCTTCTCA +TCCGACTCCATAAAGTTTAGCAGGCCACGTGGCAAGCATCTAACCAGTAG +ATCATTGGCTTGTTGGTTATCAGCAATCCACAAACTTATCAAATGCCCTG +ACAATTGCTTATTCGTCATTCTCCGTAAATCCTTTCCTACTGTAAGCAGC +GCCGTGTGTAGATGAGTCAGAAATGCTCCTTCTGACAGTGCCAACATCTG +CATCGATTTGGAAGTCTCGACGTCCGCCTCCTCGATGATAGCTCTCATCA +CCATCCCTGCGCCTTTGACAATTGTCATACTGGGACACTGGAAGAGACGG +AAGAAGCTACGACCACGTAACGCGACGAGCTTCAGGATATGATCAAAAGT +GTCGCCAGAAGTGGTCTCCGAGTATGGGGAGCAGACGGAAAAGGTCAGGA +AGTTGAGCATAGAGGCGATGACAAGCCAACCGGTGGAGCGATCCACGTGG +AGGACGATAAGATCCAAAAGGTTCTCGACAAACTTCGGACTGCTCATCAG +ACTCTGCTTATTCAATTGCTCAATCCTCAATTCATATTGATCATGCATCG +GATACATCAGTGCACACAGAGCCTCCACAGTAGAATGATCGATAGATTCG +GATTTCCACGAGAGCACACGAACTACAAGACTTCCAAGCTTCTCGCGGAC +TCCCGTGACTTCTGTGAAAGCCTGAAATCCGCTTTTCGATGCAAACAGCC +TTCTGAGACACTGTAGCTGTGCTTCTGTCTTATGCTTGTACTCCTTCTCC +TCCTTTGTATAATTCTCGCCTAGCACTGCTTCAATAGCGTTGACAATCAC +TTTTCCCTTATTTTCCGAGAAGAATCCTTCGTGAGATTTCGAGAATCGAA +GGCCTGAATACGGGACGTTGGCGTTGAAACGGCGGATGGTGTCGCAGCGA +CGAAGGCCTGGGGGCGGGGCGATGATGTGTTTCATGCATTGAGACTCGGC +ATCTTCGTCCAGTGTCGTTGAGAATGGAATCACTCGGAGATTCCTCTCGA +AGCGGTGACCGCACACGAAGACTTCTTGATTTCCAGAAGCACGGATTCCG +TCGAGAAGAGAGGCTAGGATGAGGTCTCGTTCAGCTGCCACGTACGCTCT +TCCGTCGCCGTTCTCATATTCGACGATGAATTGTTGAGGGTCTTTCTCGC +TTCGCACGAGGCAAACGATCTGGAAATATgggttttaggatttttagagt +ttttggaatttcatatttttagaatcttggaatttcagaatctctgaatt +tcagattcctggAATATCAGGACTTGAGAATACCAGAATTCAAGCATCTT +AAATTCTCGGATTCTTAGAATTTacgttttcgaaattttcagattctcga +aatttcaaaatttccgattcttgtttttgagctttttggaaatttcagat +tttcaagtttttgaaatttcagaatttcagattttcagatttttggaatt +tcagaatttaataattccagaactccagaatcttagaattttagattctc +ggattctctgattctagaaatttcagattttcagaatttttcgaatttca +gattttgagatgaaattcttagaattacgacatcgaaattttcagaattt +ttggaagtttagaatttcagattatttaaaatttcagattttcagattct +cggaATATCagaacctaaaattttcagaattacagattctcagaatttca +gattttcaaattcttggaatttcagattttcagaatcttggtgtttcagc +tttttcaaatttcggattcttggaattttctgaaattccacatttttttt +tcaaaaatctgaaattagaagcatcggaatttctgaaattccgaggatat +gtaattttgaaaatgctagaaaaatattttcaaaaatctaaaaattctaa +aattctgaaaatttgaaaactccaaaatttcgtaattaccgattcttggt +ttttgaggttttcgaaatttcagatttttagattctcggAATATTAGACT +TTCAAATTCctggaatatcagaatctaacattttcagaattacagatcct +cagaatttcaaattcttggaatttcaggttctctgaaattctatttttca +ggcgtttttctagaattttcagcccaaaactAACATGTTTCAGCGGGGTA +GCACAAATGACTGCATACGTCGCCAAGTCCCTCTCAATGATACACGTCTC +ACTCAAACACAACAGTCTCCGCACAGGCAATTCGGCTCGTCTCGTGATTT +TTGACACTTTGAATTCTGAATACGACGTCAACTCTTCGTCACGACTACAT +AATCCGAGGCGGGTCTTGAGGAAATCGTCGAGTGAGATGAGTTCTTTGGC +CATTGGAATCGTATAACCAATATTCTCAATTGCCAGACGTCGACATTCTT +TGATTAGCTCTTCTTGATTCGACGAGGCGAACATGTGCTGAAAATAaggg +attttcagacaaaaaatatagcgaaaaatccgattttcagggtctaaaat +tgccaaaaaaaaccCTGATTTTTGGCGAAtttttcgtctagaaaaggtga +taggtttttcagccatttttcagattttaggtttttcagccatttttcag +aattttttgtctgaaattctgatggAACGGCGTTCTGGATTACtgcaggt +tactgtagaaaatcccatattttgtagtttttttctcctgcaaacacaat +cacgtcaaaggttttctacagtaatctacagtaatcttcaatATCATCTC +CCGTCGATTTTCAggcgaaaaattcggaaaaaaaaagtcagattCGGGtc +taaaatgggtcaaaaaccGCCGCAAATTTTGaggaaatctaggtcatgac +ctagaaaaatttaggccatgacctagaaaaatctgggtcatgacctagaa +aaatctgggtcatgacctagaaaaatcttgtttttttcggtttttttttt +catttttttttcagaaaatcttcaaaattctgttttcgGTTTCGTTTTAG +CATTAAAACGTCAATTTATTCAAagaatttgttttaaaaatctgattttt +ggcTCCTTTTTTAGGTCATAAGTCAGTTAAAATGTGACATTTCAGGACGA +GTTTTGactctaaaaatcattttttccagccaaaaatgCTCCTTACCCGT +CTCCTATGCTCGCCGACATCGACCACAAACGCTCCGGGACAATCGGAAAT +CTTTCCGATACTTCGTATATTCTTATACGGATACATCTGCACGACGACAC +CGCGATTATCGATTTGTTCCAATCCGAAGGCGTTGGCACGGAGAGTGACT +TGGATGCGACGATCACTCCAGCTCTGTTTGAATGCTGTcactgtctgaaa +ttttggggaaaataTGAGGATTTCCatgtgtccagatgtccgaAAAGCAC +AGAAAatattacagattttcagctattttcagcttttaccgaacattttt +tgaatttttagggaCATCCAAacggcgccaaattcaaattttgagacgTC +AAAAGATCTCAGGGCCTCCAAATTTATCGTTAAAAACAAAGCTCACCACT +GGATCAAAGACCTTATCAGCGAATTTGGTATGAAATTGAAGACAGTGCGT +CAGAATGTCGGGTGTGTACTCCGATGAGAACTTCATATCGTCCTTTTTGC +CACGTTGTCGATACCAAATCTTGAAGCCAGTCTCCTCTTGACGAGTATCA +TTGGGTTGGAACGGTTTCACTGATATGAAGTCTTCGTAGAGCCACTGGAA +ACATgcgaattcagatttttagaatttttggaatttcaggtttttgagat +tctaagaattctaaaatcaaaatttttggaatttttggattttcagattt +tcagggtcttaggaatttcaggtttgcgaaatttcagaatcatcagaatt +tcagaatttcagattttcaagttttttgagcttcagattctcagattctc +gaaatttcagattttcagattgttctaattcagatttttggaatttcaga +atctcagaatttcagattcctggAACATCAGATTCTCGGatcctcagaat +ttcagaatctgagattttcagaattacaggttctcgaaatttcagatttt +cagattctaagaattccaaaattaaaattttcagaattttggaatttcag +attttcaatttttcgattttttgcaaattttctagaccttttttccggtt +atttttgtcaattcttcttccattttcccgatttttgtctctgaaaatct +taaaagattactgtagaaaacctggtattttggagtttttttaaatctgc +aTTTCGACGTGATTGGGTTTGCAgagaaaaactacaaaactttgtacagt +aatctacagtaacccaggaCACCGTttcatcagaatttcagacgaaaaaa +accagaaaaatcgaaaaatatgttttgaaaatagctgaaaaacctggaaa +tgtcaaaaattcttgatttttgcccattttcagTGGAatttcggtccgca +ttttgccatttttgatgattttccagctcatttcaccgatttttcagatt +tcaaaatgaaaatttagtGATTTCTGACGATTTTCCAGCTAGtttgaagc +caaaaatcagCATTTTGAGACATAAAATCTCAACTTTTGCCTATTTTCAG +TGTAATTCAAGccagagatttcaaaatgagaatttagatcaatttagacc +aatttttaccaatttttatCAGCCTTCTCCCAtattttcttcagatttca +aagttttcagtcaaAAGTGCTACCTGGTTAGTGATTTCCAACGAGTTGGG +ATTATAGGTTGTGATGCCAGCGTTCCGATCGAGAAAACCCGTTTGTATCT +GGAAATTTATCATTTCTACgggtagttttttttcaattttttgtcatttt +tgctcttttttaaaacctaaatttggctaaaaatcgcgaaaattcccatt +tttgactaaaaaatctgacttttttttcgaatttctgccagaaaaagctc +tttttttctgacattttcgagcccaaaaatcgctattttcgGCCATCTTT +TGCTCATTTCTGAGCccaaaaagtcggaaaatagacaattttcgactttt +ttttcgaaaattttgacatttttgactgcgaaaaccgcaattttcagcta +ttttttgctcatttctgACCCCAGAAAGTCGAAAAATAGGCAACTTTCTA +CTTTTTTGAACGTTTTAAATGCATTTGTTACATTTTTGACTGCAAAAACT +GCTCttttcggctattttttgctcatttctgagcccaaaaagtcggaaaa +taggggatttttgacacttttgacTGCAGAAATCGctattttcggtcatt +ttttgctcatttttcctctattttcctATTAAAATCCTCACTTTCCCTTC +CATGAGTGTTTGGTGACCAAGTAGCACGCGACATCGCGATTCTCCGTACA +AAACTGATTGGCCATTTCGTTCAGTTTGACATTTACActgaaaaatagcg +aaaaatccggtgaaaaatccccaaaaaacggcataaataacggaaatttc +gcaaaaaaaatgcaatttggAACTAATTAACGGCGATAATTGCGGTGGGA +AAATTggcacaaaaaagttatctCTCGAGAGAAAAATCGAGTGCGGCGGA +GCGCGTTTTCCATTCCCACGACGTTGACTCATTTGAGTAAATAGACCGGT +TTTTGTCATgtgaaacatgaaaattgataaaaatcctggtttttgagctg +aaaaatcatgaaaattgggtgatttttagaggaaaattatcgattttttg +ggggtttttgttttgaatgaaattgtATACAAAAAGTGTCGAAGGGGGAC +AGAGAGGAAGAGGAGAGACGGACCAGATTACGAAACGAAACACGTTATAC +AATTGATGGAGATCGCGAACGGAGAGGAGGAATTCTGAGAACtttttttg +cgggaaatttgaaattttttgaaaagttttgagagcgaaaatttgaaaaa +ttgcgagtctacaattggttttttgaataaaaattttaattttaaatttt +tttttggattttttcgagaatattcagttattgttttttttctgtcctga +aaaaaattcagccgctggctaaattttgaagtgtgaaaatctgaaaaaat +ttgaatttttaattttttttttcgaaaattttaaatttgcttgaaactcg +attttttaccagatttttatgacaaatttgcgtattttaaaaattttttc +gatgttttgtttcggaaaatcgaCCATCGCATCGGCACAACCTTACAGAT +TTctcattagaaaaaaagggtGTTACAACCTAAgcctcaaatttcaaaca +aaaaggcaaaataatctgaaaactccaatcaaaaagtctttaaattccca +aaTattagcaaattttacactttttttagcaaattttacactttttatta +gcaaattttacacttttttcactgcaaaattttcagaatattccgttttt +tgttctatattttAGGCCTGAGGCTAAAACACCTTTTTTACGACAAGAAG +TTTCATTCTAAGCCTTTGTATGAACAAAAAACACGGAACATCCTGAtcat +tttcagggaaaaaagtgaaaaaatagaggtgggcGGGATTGCGCTCCACC +GAAATGAGCAGTTTCGTTTGTGAAATTCCGTCGctgttctggaaaattcg +aatggaaattcgaaaaataccctttctcttttttcgaggtttttctaaat +tttcagatttttctcgcACTTCTGTCGCTgaaaaaaagcactttataacg +aaaaatctgaaaaaaaggaaaatccgggaatttgaaaaacctcaattttc +agattttcagacgcATTATCTTTCACTTCAgacttattttcagaaaaata +ctaaaattatTAATTCACTCTATGaagaaaaacctgaaaattccatCTAA +AATCTAGAATAACCCACTCAAATTGATGAGAcacaattctcattttttga +aaaaaaaaacgttgctCGTCAATTAAAGTGCAAAAAATTGCGAACACCAC +CACGCAAAATCACACACACcggagagaaaaaatggagggagatttgaatt +tttcaactttttcagagaaaagtgattttcaggCAATAATTCCAAACAAA +ATGGACACCCGGACACACAAAcagacctgaaaaaaacaaattttacacat +ctagaatttccaatttttgtgacCATTTCCTGTCATTTTCTGTccttatt +ttccaatttcctgcTTTCCCACACATTCCAAATTAGGCACATAGGCATAT +AATACGCCTCCTTTTCCCCCCTAgtttattccaattttccatgGCAACCA +GAAGCAGACACCTGCAGAGGTGAAACTAGCgagagggagaaagtgtggga +gatgaagagacgcagagaaagagagagggaggaaatagggagaaCGTGCT +CTCATTATGCGCTCTTTCAAGAGCCCAAGAAGCTGTTGTGCACTTAGATT +TCTGCAAAATAcctttattttcattttgcaagaattttcttagattttta +acctttataaaatttaaattcaaaatttgataaaatgtaaATTCGCTCTA +CTgttaatctaattttttttcaaactttcttttttaaaaacggattaaac +ttgcgtttttttGTGAATGaaaaataaggcaaaaagtagtttttccttca +aaaaaatttttaacataaaaaaaagatttttagcaaatgcgctctaatga +aaaaaggtttttgaaaattatcattagagcgcatttccTCAGTgaatttg +tttgtttttaaaaacttcccATTTCCCTATAATCGTAGAAACAAAATAAA +CAAAGCCtgaatatcaaatttccaattttcatattctaaattttctagaa +ttttccagaaaaatacaaaattttggggacaatttttttcagaaaaataa +ccatggcatctgaaaataaggaccaacgaaaatcgtattttctcCGGGTG +GCGTCTTATTTGCTCGGATTGAATATTGTTgaggaaaagttgaaaaatac +agaGCCATTGGAGACTTTTCTAGACTCAAACACCAATTTATTGGTTTTCT +CGCGGTCTGAACAGGTTGGTTTTGTTAGAATTGGATTCAGCTTgttgaaa +gcttcaaaatgagcctaaacacgactatattCCTTTAAAagttgggtccc +accacgaaaggtacagtaatccccaaaaaaaaccgaaattgaCCTAGATA +TGTCGCGgttaagctcattttgaagctcatactgtgctgaaaaataataa +aaaaatttcatgaagaaatatccaaaaataagcaaattataagaaattta +agatttcctaaaattttcaaaaaatcaatttgtgtcataatttttgtatt +tttgattttctttgaaCGAACTCATCGTATTTCAATTCAGTTTGAtgagc +gcttcaaaatgagcctaaacacgactatattCCTTTGAAAGTTGGGTacc +accacgaaaactacagtaatctcgaaaatttccaaattgacCTAGGTATG +TCgagtttaggctcattttgaagctcttgacacGCCTAAAACGATTTTAG +TAATTTAATGTTTAAATTTAGAAACATAAGGGAGATataagaatttttag +attttctttaaaatttttttgaaaatcaatttttcgccacaattcggtta +tttttgaacttttcagactgaaacctattttttctaattgggCTCAataa +atgcttcaaaatgagcctaaacacgactatattCCTTTGAAagttgggtc +ccaccacgaaaagtaccgtaatcccacgaaaaatcaaaatgcagctagac +tagtcgtgtttaagctcattttgaagctctgaacaaGTTGAAAAGAAATA +GACTATTGTTGAAGagcaaatctcaaaattaaagaagttttcgaagtttg +aaaatttacgaaaaaaaaactcccaaaattaaatgttttcagaaactgGA +ACTCTCCAACAAAATGAAGTCTTCTGCTCCATCGGCCAATGTCCTCCGAG +TGGTTTTCTACAAAACGCAGTCTGTCCCTTTAAACAATGAGAACTTCAAA +AGTGTGGTCAATGTGATATCAGCCAATGGAACCCTGAATCATGTCTTTTT +GAAATCCGTTCAGAATGTAACAAACattctcattagagcgaattttcata +attttgaaattctaggttTTCGGAAAAGAACTCACCGAGGGTAACAACAT +GCAACTGATTGCGGCGGTCAATGAACTTGAGGAGAGTTTGCTGGCTACTG +TGGAAATGAGTGGaggtaagtgcgctctattgataaattTGTATTCAgct +cgttgagagcttcaaaacgagctcCAACACGACATATCTAggccaatttt +gaatttttcgggattactgtagttttcgtggtgggatcCTATTCAACGGA +TTAcggtcgtgtttgggctcattttgcagcattttttaactttaatgaaa +actttttaatttcGTTAAGAGAAAATCCAAACTATCGAAATAATGACAGA +AAAACGAtagtcaaaactttttcagaaaatctgaaatttcttaaatttcg +cctgtttttgaaatattgataTAAAATTATTGTGTTCTGATTCAGCgtgt +caagagcttcaaaatgagcccaaacacgactagtctagctacattttgat +attttgtaggattactgtacttttcgtGCTGAGACCCTATTCAACGGAAT +ATGGTaatgtttaggcttattttgaagggTTTAAAACACCAAACTGGAAT +AAAAAACTTCGATTTAGAAcattccaaaataaaataattcaggcgaaaaa +ttgattttccaaaaattttcagaaaatcataaatGTCTTTAAATTTGCTT +ATTGCTTTTAAATTCaaccaaaaattattttgattttttcagctcgttga +gagcttcaaaatgagcccaaacacgactagtctagcacacatttgatatt +ttgtagggttactgtacttttcgtggtgggacccaattTTCTTATATTCA +AAAGGAATgtggtcgtgtttgggctcgttttgaagtttcaacttcaaaat +ttcaacatttcacctcaaatttcaattttctgactttAGGAGGTTCTCTA +CACGATGAGATTCGAAGTTGGAAAGGACAATCGGGACGGGCGGCCCAGGA +CTATAACGATGCGTTCAAACAACTACAATTACTTGTGGAGACGATGGAGG +AAAGACGAATTGATGAGTTATCAGAACTTGTAGAAACATTTGAAGACACT +TGTGATGAATTATGGAATTGCGGAGTACCGTATCCCCAGCCAAGGATGAA +GATGCTGATCGAGTACGGATCGAGTTATTTGTGTGAGGCCATTACTTTCA +AAGTATGTGCCTATTTTAAGattttgttttggaatttctaggaaTATCCA +CTTAACAGAGCGTTAAGgctcatttttgtatttttcaacttttttctagc +ttttctagttcttgagatataaTCATATGAAGGTTTTCACAGTCTGTTAA +GGGTGTCttaattttgacctaatttatctcacttcttttgaaagatatca +aaaagtggtcaactgataaaatgtttatcataatatcagcaacattttat +caattgattacTTTCcaatatctttcacgggaagctagataaattgaatc +aaacTTTTAATATAAATGTTTGGTtatgaaaaccaattttctgtCCAAAC +TCTGctatttctgaactttctgttttgaaattgtaatATTCTAGTTTGTC +TAGTTAagctcttcaaaatgaatctAAACACAACTATATCTCTTCtgaat +tgaggaaaattggggTCCCAATacgaaaagtacagtaatcccacaAAAAC +TCCATAATTTTTCTATACTaggcgtgtttaggctcattttgaagctctta +atgTGATCAAGAATATGAAATTGGCTGAATGtcagaattttgggaattaa +GGCAATTATAAAGAGTTTATAAAAATTAGCTAGATGTTCTAGTGTTGGAG +ATATGTGTTTGCGCTCAAAGACGACATTCGAGTTAAAAGAAGGAGAATGT +CATCTTTAAGcgcgtatatctcaaaaaccaataaatttagaaaaacgttg +tcaactagagaaatgtacaaaattttatgggctacacttttgtagtttac +aaaatgAAGCTAGCTatcttagtttttgagatatttacCTCCAAAGTTAC +AACACTcttcttttggaatttgaagtAGATAAACGCTATTTTTGAGcgcg +tatatctcaaaaactaatgaatctataaaaaagttgtcaattgacaaaat +gtgtgaaatgttATGTGctatgtttttgttgtttgccAAATTTAGCTagt +tattttggtttttgagatataaccCTTCAAAACTAGAATACACTTTTATC +CCGCGAGTCGAGTCATGAGTCAGAGATgccttaaaattgaaaacctaTAA +CAAATTGCAGATCGATGACTCAGCGATCTGGCGAGACGAAAAAGTGTCGG +ATCAGTTGCGATCAGCAATCGATGTGTGTGATCAAATGCTGATCGTAATT +CGTCTACTAACATCTCAAACCTGGAAACGAAACGTCGAGCACACATGGGA +AGGCGATCCGATGGAAATGAAGTTTCTCAATGGTTTCAAAGAACGACTCG +ATGAAATTCTGTCGCTTCGAAGTCTGGGAGGCCAGTTGGAAGGACTTTTG +GAAGAAAGGGGCATTCGAGAGGAGACCGAAAAAACGATAGAGACGGCAAT +GAGAGGAATGGCACCAATGGCATATAATCCGTTTACGGAACCCAATTGGA +AGAGTCGACTGCTGGTGGCGGAGAGGGCGATTGAGGGGACAATTGATAGG +ACGCTGCCGATTTTAAAGCAGAGACTTGCACCGAGTAATGGAGATAGTCA +GAGTGTAAGTAGCCTGGAATTTCACAAGGTCATCGGGGACCAATAAGGCG +TTTTAAGCTCGGAAGACTCAAAAACCCCTAGAGTCACTCTCCGGCgcata +actcggttcaaaattgaaattcgtgtttgaattaaaaagtgaaacgTAGA +GTTTGACAATATCTACAAAATAATATTGAATTCGACTACTTTGGGATGTC +aagttctgaaataaaaaattttaaatagcAAAGTCCGCCAGAACGCGGGC +CCGGCTACTCTGCGGCCTCTGGTGAAACACTCGACATTTCAATATAGTAG +GTttgaatatcattttgtagatcttgtcAAGTGCTAAATTCTAAGTTtag +ttttgttcaaaaattccatttttgcgCCAAGTTATGAGCCTCTAAAGTTT +GATCTCCCTTGAAGCGCGCGCtgtcgcttctctgcgtctccccttTTCCT +CTactatctcaaaaactattgtcggaataaaaaaagtgagactcggtgtt +tgcgtactttgattcccgcctccccccaccgacgctccgcccatcgcttt +gcaagtgcggcgtggtgttttggCGCTACTTGGGAGATCATCGGatttaa +tgagattttcatagaaaatatgaTCCCCAAGTGGCGCGccaaaacaccac +gccgcacttgcaaagcgatgggcggagcgtcggtggggggaggcgggaat +caaagtacgcaaacaccgagtctcactttttttattccgacaataaaata +gctatgaaaaagttgtcaactagtaaaatgtgtaaaattttaaaatctct +atttttctagCTTACAAAAGTTTTGTAGCGTGTTTAGTTTAAGAGATACT +AGCCCCTGAAGTTGAGGCGCCATTCAAGTTGTACAGACAatattgaaact +tttgaatctcATAGAATAATAGCGCTAAActaaaattttaacaaaatgtA +GATCAAAATGTTTTACATATTTTGCTAATTGGCAAAATTTAGTTAGCGTT +TTTAGTTTTAGATGTAGACACTTTTAAATTGTTATCTACTTTGAAGCGCG +TTGTTATCTACTTTGAAGCTCTGCCGCCTCTCTGCGCCAAAACGCATATC +TCAACAACTAAAAACgctattaaaaagttgtcaactaacaaaatatagcc +cacaaaattttacacattttactaatttttaactttttgctAGTTATTTC +ATTTCTCGAGTTATAGGCGTTTAAAGTTTGACCTACTTTGTTGCGCGCCC +TATCGCACCTCTGCGTCTTTCTTCGACTTCAAAAGCGCGTATCTCAAACA +CTAGAATAGCtagtcaaattttaaaaactacaaaagtgtaGCCCATAAAA +TTatatacatttttctagtttacaacttttttctagctattttaaCTCTT +GAGTTATAGGCTTTTAAATTTTGACCTACTTCACTGCGCGCGCTCTCACA +TCagttttctgcgtctctctttccgtttaaaggcgcatatctcaaaaact +agaaaagctatcgaaatgttgtcaactacaaaaactttcaaaattttatc +agctacttttttatagtttacaaatttcagcTAGCTATTCTAGTTTTCAA +GATAATCGTTTCCAGATCGTTCTAAGCctggaaaagctgaaaagcTTCCT +GTGCCGAGCCAACATCAAGGAGAAACTTCAACACGAGCGGGAAATGTTCC +TGAATCGTTTGATATCAATGCTATCAcagaaaaatcaggaattcagCGAG +AAATCTCTTCAAGTCGAcgctaaaaattttcaatttctcacaGAAGTCGC +CGCGAGAATCGTCTGGATTCGGCAGCAGACAAGTCAGGTAAAGGACATat +ggacaaacagacacacagcttttttttttaaatttctttagATGGAAAGT +ATCAGATCGCTGTCGAAAATGATGTTGAACGATATCTCGAACTACAATCA +ATTCGCACAAAAGCTGgatgaatttattgaaaaactacagtatgccGAGA +AGGAGTGTTTCGATGATTGGTGTCGAGAAACCGTCGGGTTGATTGATAAT +AAAAATGAGACGATAAATCTAGAAACGACTGGAAAGATTATGTATTTGGA +AGCGTCGAATCGAGAGTTGAATGTGAACTATTCAGATCGTCTTTTGAGAT +TGTTGAAggcatggcctaactttttttctaggccatgtaatctctttttt +ccaggaagTCCGCCAACTGAGCAGTTTGGGATTCAACATTCCATCGAAGA +TCCTGTCATGCGCTAACAATGGAGAGAAGTACTATCGATTTGGTGTTATC +CTCAAAcagattgctcatttttataaTACCATCGATCAACAGATGATTCC +GTCGCAACAGGTAAGCATGATTAGCTTTAGAAGCGCATTTCTCTAAAACT +AAAATAGTTAACAAAAAGTTATCAGCTAttaaaatgtataaaatttttat +agactATATTGCATTTGCTaaaaaaaTTCAGCTAACTATTTTAGTTCATG +AAGTATTAGGCTTCGAAGTTAGGGCACATTTTTGTCCCGCGAGTCCGTTT +AAGAAAAGTTTaccttttggaaatttttggattttcggctgtttttttca +aaaatatggaaaaattggatcatgacctaaaaaaatctaggtcatgacct +gggaaatttaggtcatgacctgggaaatctaggtcgtgacctagaaaaat +taggtcatgacctaaaaaaatctaggctatgacctaaaaaaatctaggct +ATGACCTgtaaaatctaggtcatgacctaaaaaaattgagccatgatcta +gaaaaattgggtcaagtttttagtttttgagttatacGCTTTCAAAGTTT +AAGCATCTCTGACTCAGGACAAACGTGCATCCTAGTTTCGGAAgtttata +tctcaaaaactacaatagctagcaaaaatttgtcaactacaaaatttttt +gaaattttaagagctatATTTTAAGACTTAACACATTTTAACTAGTTATA +TTAGCTTCAGAGATATTCGAGTTAGAAAGCGCGCGCTCTGGATTCTCTTT +GGTTCCAACTTTCTTTTACTTTGTAGACgcatatcttaaaaactaagaca +gctatcaaaaagtcgctaactagtaaaatgtttaaaattttatgggcttt +atttttgtagtttacaaaatttaccTAGCTatcctagtttttgagatatt +catGTTGAAAGACAACccacttgaaaattttatatctcaaaaactagaaa +agctatttcaatttgattttcagtctcTCATGCTGGAAGAAGCAATTGCA +TTTGAAAAACTGGTTATTCCAAGGAAGGATGCCTCCAACTCGGCTTCGAA +AGTAACATGGAACGATCCAAAACAACTGGAAGAGTTCATTGTCCAACTGC +AAACCGCCGAACAAAAATTGTCGAATCGAAACCGTCGGTTGCGAAATGTT +CATATGGAATTGATAGAAATGGTTGAGAAATTGATGGATTTGAATATTGT +GAAACAGAATAATGAGTGGAAAGAGATTATTCTGAAGATTCGATCGAAAA +TGAAGGAGGAAGAAGTTGTACATGGAGCGGCGAGGAATAATATGAAGCCG +TGGTTGATTCATTGGGATTTTCAATTGTATAAGGTGATTTGGCTCTACTG +TAGAATTTGGGcctcaaaaataaatatggtCCTTGAAGACAATTTTGGTc +cgaggtttttgaaaaattcggaacttcagaaattcagaaattcagaaatt +cagaaattcagaaattcagaaattcagaaattcagaaattcagaaattca +gaaattcagaaattcagaaattcagaaattcagaaattcagaaattcaga +aattcagaaattcagaaattcagaaattcagaaattcagaaattcagaaa +ttcagaaattcagaaattcagaaattcagaaattcagaaattcagaaatt +cagaaactcagaaattcaggaaatcaggaaatcagaaattcggaaattcg +gaaattcagaattttagaagttcagagaatcagaatattagaagttcaga +aattcagaaattctaaagttctagaattctacaaattcaaaattttgaaa +attcaaagttccagcaattcagaaaattaaaaattcgggaattcaaaagt +ttccagaatctcaaaatcttagaaatcaaatattctgatatttttttaaa +aattccagaaaagtcTAAATGtacagaaattctaaaattctaagattcta +aatttctagaattctgaaaattcaaaaatccagcaattcggaaattccta +tttttcttagggttttcagaatttcaaaagttctttaaaaatttcaaatt +gttcaaATCTTCAGGCTCTTCTAATCCAATACGAATGGGGAATCGAAAGT +ATCCAATCTCAATTATCCACAATTTCCGTCAGTCTAGTTTTTGTGTaagt +gtcgatttacgggctCTTTGATTCCtcgattttcggtttttcagcGATCA +AAAAATCCAACTGCGTCCGGCAATCGAAGAAATCCGTTCCAAATATTACA +AAGAGCTCTGTCGATTTTTAAGAATTCCAGACAAATTTCGAGGAGTTCAG +GAGGATGAGACAgtaagtgcgctccattgataatttctgtttttctgaat +ttctagaatttcaaaatttagaatttctgaatttctgaatttagaaaaaa +ttgtgttttagTCAACCAAATTCTACGCCCAAATGATCGAACGAAGTATG +CATTTGTTGCCATCAGTCTACGAGAAAGCTGAGCAATTGATGCAAAAAGT +GGAGACTTGTGATGCCATTTTCGTGGTATGCTTATcggtttgtccggatg +tccgcaattgaaaaaattttcaggattggCTAGTCATCTCCCAAGTGGAC +CTCGAGGAGCTTattgaggaaaatttgaaaaccgcAGCGGATTGGGAATC +GCAgtttaagattttgaaagcCAAAGCAAGAGAGGCCGAACGTTTGCCAC +AGTAagattggattactgtactttagaaaattcgaactGCAAGTCATTAA +GACTTTGGTTCAATTAGATTACCGTACATTTGTTCTAGCAAAGCATTTTG +TTCATCACAGAGCGCACAGGGTTTGTTTTTCTATCTTTGCAAACTCGTTC +TATTGATAAGGGGCGGGGCGAagctttttctaattttcaaaaatgaaaaa +attctcccCTAAAACGAGAGATCTTGTTTCGGTGAAGAGACTCAGAACAT +TTCTGTGAAGAGACGAAATTTcggtgaagagacgcagacaacgaaacgaa +acgtttgatcctcagccatcGATTTGGCTGCGTTCTCATTAAAGCGCATT +CACAAAGATAGTAAAACAAACGCTGTGAGAGCGTTTGCGAGGCTTGCAGT +TCGGTTTTGTTAGCTGCAGAGATTACTGTATATTTCTTTCAGTGAACTCA +AATTCGAGTGCATATTGGTGAGTACTGCTGGTGTTAAAACTGCAATCGAG +GATGCGATTCAGAGATTGTACGATGCGCTGACATGGACTTTAAGGTAAGT +AGGACATCTGGACACGCAAACACACagaaaacccaaatttcagacactCC +ATCTCCACGACGTCCACCTCTATAAGCACATTTCTCTCTCAAGCTATCGA +AGTCCTGAATACAGTACCCGGATCCTTGGATGAAGTCGCCGAGGCCAATG +CGAAACACGTCATCTTTGCTGAAACGAATCgtcagctgaaaatggaatgG +AAAGTCATGGAGGAGCAATTGACACTGTTGAGATCAGTTGCTGGTCAAGG +AATGGAGCAGATTGATAACTTGGAACAAACATGGGATCGATTTGAGCTGA +TGTTAGATGCGCATCAAGGAGTTATTAAGGAACAAGTCGAGGCGTTGAAG +GTAGTTGACCcctaaaagaagaaaagtttgacccaatttatctgggttct +tgtaagagatatcataaacgtgtcaactaataaaatgttggagatattat +gataaacattttatcagttgacaaatttttcatagcttttaagggaacag +agataaattaaTTAGGTCAAGTTTGGGTCAAAATTGGGTGTAGGTAACTT +CAAGCttgcatatctcaaaaactaaaatttctagacaaaatttgaaaact +aacaaaatgtagctcatgaaattttatacattttactagtttttaacttt +ttgatatctcttctagcaacaatcaaaaatttgacccAAAACCGCAATTT +CCTTCCAGACCAACGTTGAAACATCAATCAAGGGAATGAAGGATGAGGCG +GAGAAGCTGAAAGCGAGATGGGACCAATTCAAGCCAAGAAGTGATGCATT +ACAAGGCGATCGAGAGGAAATGCTAAAAGCGATTCAGTTTATTAAAGAAA +AACGAGTTCAGTGGCAAGAGCTGAGTGAtggaagagagaaaattgaGTGA +GATGTTTTGGTTGTTTTACTGTGAATGTTCTTGAGGCACATTATCTCCTA +TAAGcgatgttaaaaatttttcaactaaaaaatgtttctgataacttgat +aaacattttattagttgatcattttttgatatctcttaaagaaattgaga +taaatgatCTTAAAGTCGGCAAGCACAGTTGTGGCTCAGTCAACGGCGAC +GGCCGCGTCGCAGACCATAACGGCACGtattttgagcctaattatctcgg +ttcctataagcgatattaaaaatttttcaactaaaaaatgtttctgatat +cgtgataaacattttattagttgatcactttttgatatctctaatagaca +ttgagataattaagcttaaagtaGGTAAGCCCAGTTGTGGCGCAGTCAAA +GGCGCCGACCGCGTCGCCAGTGGCGgcttttttgagcaaaattatcttgg +ttgctttaagagatatcgaaaatctgtcaactgataaaatgttgctgata +atgtgataaacattttattaattgaccactttttgatgtctgttatagaa +attgagatagtCAAGCTCAAAGTCAGCAAGCACAGTTGTGGCTCAGTCAA +CGGGGCCGACCGCGTCGCCAGTTGCGGcgcattttttgagctaaattatc +ccagttcccataagagatatcaaaagttggttaactaaaaaaatgttgct +aataatgtggtgaacattttattagttgataactttttgatatctcttat +agaaattgagataatgcAGCTCAAATGACAAGTAAAAAGTAGCGGTCTTT +CGTACATGCTTTGCTTCGCTATGATACATATCTCGTTAGGGCGCATTTGC +ACAAAAATGTTGTCAGGTACAAAAATGGAGCTCTTTTCCTGTTAAATATa +atccaaacttttcaaaacaataGAACAAGTACTAAGTACGTTTGCAGCCG +CTCAAAATTAGCACATGGGTGAAACGTAAGGATCGAGGCCGCTACCTAAA +TGAACCTCGATAGCTACACTTCAAGCCTAATAAACTCAgttaatataccg +taaaacctctaatagaacgacacccgaatcgtccactttgagcctatata +tctattttctgtgaaagatannnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnaaaaTTTAGTTAGCGTTTTTAGTTTTAGAT +GTAGACACTTTTAAATTGTTATCTACTTTGAAGCGCGTTGTTATCTACTT +TGAAGCTCTGCCGCCTCTCTGCGCCAAAACGCATATCTCAACAACTAAAA +ACgctattaaaaagttgtcaactaacaaaatatagcccacaaaattttac +acattttactaatttttaactttttgctAGTTATTTCATTTCTCGAGTTA +TAGGCGTTTAAAGTTTGACCTACTTTGTTGCGCGCCCTATCGCACCTCTG +CGTCTTTCTTCGACTTCAAAAGCGCGTATCTCAAACACTAGAATAGCtag +tcaaattttaaaaactacaaaagtgtaGCCCATAAAATTatatacatttt +tctagtttacaacttttttctagctattttaaCTCTTGAGTTATAGGCTT +TTAAATTTTGACCTACTTCACTGCGCGCGCTCTCACATCagttttctgcg +tctctctttccgtttaaaggcgcatatctcaaaaactagaaaagctatcg +aaatgttgtcaactacaaaaactttcaaaattttatcagctactttttta +tagtttacaaatttcagcTAGCTATTCTAGTTTTCAAGATAATCGTTTCC +AGATCGTTCTAAGCctggaaaagctgaaaagcTTCCTGTGCCGAGCCAAC +ATCAAGGAGAAACTTCAACACGAGCGGGAAATGTTCCTGAATCGTTTGAT +ATCAATGCTATCAcagaaaaatcaggaattcagCGAGAAATCTCTTCAAG +TCGAcgctaaaaattttcaatttctcacaGAAGTCGCCGCGAGAATCGTC +TGGATTCGGCAGCAGACAAGTCAGGTAAAGGACATatggacaaacagaca +cacagcttttttttttaaatttctttagATGGAAAGTATCAGATCGCTGT +CGAAAATGATGTTGAACGATATCTCGAACTACAATCAATTCGCACAAAAG +CTGgatgaatttattgaaaaactacagtatgccGAGAAGGAGTGTTTCGA +TGATTGGTGTCGAGAAACCGTCGGGTTGATTGATAATAAAAATGAGACGA +TAAATCTAGAAACGACTGGAAAGATTATGTATTTGGAAGCGTCGAATCGA +GAGTTGAATGTGAACTATTCAGATCGTCTTTTGAGATTGTTGAAggcatg +gcctaactttttttctaggccatgtaatctcttttttccaggaagTCCGC +CAACTGAGCAGTTTGGGATTCAACATTCCATCGAAGATCCTGTCATGCGC +TAACAATGGAGAGAAGTACTATCGATTTGGTGTTATCCTCAAAcagattg +ctcatttttataaTACCATCGATCAACAGATGATTCCGTCGCAACAGGTA +AGCATGATTAGCTTTAGAAGCGCATTTCTCTAAAACTAAAATAGTTAACA +AAAAGTTATCAGCTAttaaaatgtataaaatttttatagactATATTGCA +TTTGCTaaaaaaaTTCAGCTAACTATTTTAGTTCATGAAGTATTAGGCTT +CGAAGTTAGGGCACATTTTTGTCCCGCGAGTCCGTTTAAGAAAAGTTTac +cttttggaaatttttggattttcggctgtttttttcaaaaatatggaaaa +attggatcatgacctaaaaaaatctaggtcatgacctgggaaatttaggt +catgacctgggaaatctaggtcgtgacctagaaaaattaggtcatgacct +aaaaaaatctaggctatgacctaaaaaaatctaggctATGACCTgtaaaa +tctaggtcatgacctaaaaaaattgagccatgatctagaaaaattgggtc +aagtttttagtttttgagttatacGCTTTCAAAGTTTAAGCATCTCTGAC +TCAGGACAAACGTGCATCCTAGTTTCGGAAgtttatatctcaaaaactac +aatagctagcaaaaatttgtcaactacaaaattttttgaaattttaagag +ctatATTTTAAGACTTAACACATTTTAACTAGTTATATTAGCTTCAGAGA +TATTCGAGTTAGAAAGCGCGCGCTCTGGATTCTCTTTGGTTCCAACTTTC +TTTTACTTTGTAGACgcatatcttaaaaactaagacagctatcaaaaagt +cgctaactagtaaaatgtttaaaattttatgggctttatttttgtagttt +acaaaatttaccTAGCTatcctagtttttgagatattcatGTTGAAAGAC +AACccacttgaaaattttatatctcaaaaactagaaaagctatttcaatt +tgattttcagtctcTCATGCTGGAAGAAGCAATTGCATTTGAAAAACTGG +TTATTCCAAGGAAGGATGCCTCCAACTCGGCTTCGAAAGTAACATGGAAC +GATCCAAAACAACTGGAAGAGTTCATTGTCCAACTGCAAACCGCCGAACA +AAAATTGTCGAATCGAAACCGTCGGTTGCGAAATGTTCATATGGAATTGA +TAGAAATGGTTGAGAAATTGATGGATTTGAATATTGTGAAACAGAATAAT +GAGTGGAAAGAGATTATTCTGAAGATTCGATCGAAAATGAAGGAGGAAGA +AGTTGTACATGGAGCGGCGAGGAATAATATGAAGCCGTGGTTGATTCATT +GGGATTTTCAATTGTATAAGGTGATTTGGCTCTACTGTAGAATTTGGGcc +tcaaaaataaatatggtCCTTGAAGACAATTTTGGTccgaggtttttgaa +aaattcggaacttcagaaattcagaaattcagaaattcagaaattcagaa +attcagaaattcagaaattcagaaattcagaaattcagaaattcagaaat +tcagaaattcagaaattcagaaattcagaaattcagaaattcagaaattc +agaaattcagaaattcagaaattcagaaattcagaaattcagaaattcag +aaattcagaaattcagaaattcagaaattcagaaattcagaaactcagaa +attcaggaaatcaggaaatcagaaattcggaaattcggaaattcagaatt +ttagaagttcagagaatcagaatattagaagttcagaaattcagaaattc +taaagttctagaattctacaaattcaaaattttgaaaattcaaagttcca +gcaattcagaaaattaaaaattcgggaattcaaaagtttccagaatctca +aaatcttagaaatcaaatattctgatatttttttaaaaattccagaaaag +tcTAAATGtacagaaattctaaaattctaagattctaaatttctagaatt +ctgaaaattcaaaaatccagcaattcggaaattcctatttttcttagggt +tttcagaatttcaaaagttctttaaaaatttcaaattgttcaaATCTTCA +GGCTCTTCTAATCCAATACGAATGGGGAATCGAAAGTATCCAATCTCAAT +TATCCACAATTTCCGTCAGTCTAGTTTTTGTGTaagtgtcgatttacggg +ctCTTTGATTCCtcgattttcggtttttcagcGATCAAAAAATCCAACTG +CGTCCGGCAATCGAAGAAATCCGTTCCAAATATTACAAAGAGCTCTGTCG +ATTTTTAAGAATTCCAGACAAATTTCGAGGAGTTCAGGAGGATGAGACAg +taagtgcgctccattgataatttctgtttttctgaatttctagaatttca +aaatttagaatttctgaatttctgaatttagaaaaaattgtgttttagTC +AACCAAATTCTACGCCCAAATGATCGAACGAAGTATGCATTTGTTGCCAT +CAGTCTACGAGAAAGCTGAGCAATTGATGCAAAAAGTGGAGACTTGTGAT +GCCATTTTCGTGGTATGCTTATcggtttgtccggatgtccgcaattgaaa +aaattttcaggattggCTAGTCATCTCCCAAGTGGACCTCGAGGAGCTTa +ttgaggaaaatttgaaaaccgcAGCGGATTGGGAATCGCAgtttaagatt +ttgaaagcCAAAGCAAGAGAGGCCGAACGTTTGCCACAGTAagattggat +tactgtactttagaaaattcgaactGCAAGTCATTAAGACTTTGGTTCAA +TTAGATTACCGTACATTTGTTCTAGCAAAGCATTTTGTTCATCACAGAGC +GCACAGGGTTTGTTTTTCTATCTTTGCAAACTCGTTCTATTGATAAGGGG +CGGGGCGAagctttttctaattttcaaaaatgaaaaaattctcccCTAAA +ACGAGAGATCTTGTTTCGGTGAAGAGACTCAGAACATTTCTGTGAAGAGA +CGAAATTTcggtgaagagacgcagacaacgaaacgaaacgtttgatcctc +agccatcGATTTGGCTGCGTTCTCATTAAAGCGCATTCACAAAGATAGTA +AAACAAACGCTGTGAGAGCGTTTGCGAGGCTTGCAGTTCGGTTTTGTTAG +CTGCAGAGATTACTGTATATTTCTTTCAGTGAACTCAAATTCGAGTGCAT +ATTGGTGAGTACTGCTGGTGTTAAAACTGCAATCGAGGATGCGATTCAGA +GATTGTACGATGCGCTGACATGGACTTTAAGGTAAGTAGGACATCTGGAC +ACGCAAACACACagaaaacccaaatttcagacactCCATCTCCACGACGT +CCACCTCTATAAGCACATTTCTCTCTCAAGCTATCGAAGTCCTGAATACA +GTACCCGGATCCTTGGATGAAGTCGCCGAGGCCAATGCGAAACACGTCAT +CTTTGCTGAAACGAATCgtcagctgaaaatggaatgGAAAGTCATGGAGG +AGCAATTGACACTGTTGAGATCAGTTGCTGGTCAAGGAATGGAGCAGATT +GATAACTTGGAACAAACATGGGATCGATTTGAGCTGATGTTAGATGCGCA +TCAAGGAGTTATTAAGGAACAAGTCGAGGCGTTGAAGGTAGTTGACCcct +aaaagaagaaaagtttgacccaatttatctgggttcttgtaagagatatc +ataaacgtgtcaactaataaaatgttggagatattatgataaacatttta +tcagttgacaaatttttcatagcttttaagggaacagagataaattaaTT +AGGTCAAGTTTGGGTCAAAATTGGGTGTAGGTAACTTCAAGCttgcatat +ctcaaaaactaaaatttctagacaaaatttgaaaactaacaaaatgtagc +tcatgaaattttatacattttactagtttttaactttttgatatctcttc +tagcaacaatcaaaaatttgacccAAAACCGCAATTTCCTTCCAGACCAA +CGTTGAAACATCAATCAAGGGAATGAAGGATGAGGCGGAGAAGCTGAAAG +CGAGATGGGACCAATTCAAGCCAAGAAGTGATGCATTACAAGGCGATCGA +GAGGAAATGCTAAAAGCGATTCAGTTTATTAAAGAAAAACGAGTTCAGTG +GCAAGAGCTGAGTGAtggaagagagaaaattgaGTGAGATGTTTTGGTTG +TTTTACTGTGAATGTTCTTGAGGCACATTATCTCCTATAAGcgatgttaa +aaatttttcaactaaaaaatgtttctgataacttgataaacattttatta +gttgatcattttttgatatctcttaaagaaattgagataaatgatCTTAA +AGTCGGCAAGCACAGTTGTGGCTCAGTCAACGGCGACGGCCGCGTCGCAG +ACCATAACGGCACGtattttgagcctaattatctcggttcctataagcga +tattaaaaatttttcaactaaaaaatgtttctgatatcgtgataaacatt +ttattagttgatcactttttgatatctctaatagacattgagataattaa +gcttaaagtaGGTAAGCCCAGTTGTGGCGCAGTCAAAGGCGCCGACCGCG +TCGCCAGTGGCGgcttttttgagcaaaattatcttggttgctttaagaga +tatcgaaaatctgtcaactgataaaatgttgctgataatgtgataaacat +tttattaattgaccactttttgatgtctgttatagaaattgagatagtCA +AGCTCAAAGTCAGCAAGCACAGTTGTGGCTCAGTCAACGGGGCCGACCGC +GTCGCCAGTTGCGGcgcattttttgagctaaattatcccagttcccataa +gagatatcaaaagttggttaactaaaaaaatgttgctaataatgtggtga +acattttattagttgataactttttgatatctcttatagaaattgagata +atgcAGCTCAAATGACAAGTAAAAAGTAGCGGTCTTTCGTACATGCTTTG +CTTCGCTATGATACATATCTCGTTAGGGCGCATTTGCACAAAAATGTTGT +CAGGTACAAAAATGGAGCTCTTTTCCTGTTAAATATaatccaaacttttc +aaaacaataGAACAAGTACTAAGTACGTTTGCAGCCGCTCAAAATTAGCA +CATGGGTGAAACGTAAGGATCGAGGCCGCTACCTAAATGAACCTCGATAG +CTACACTTCAAGCCTAATAAACTCAgttaatataccgtaaaacctctaat +agaacgacacccgaatcgtccactttgagcctatatatctcacttctttt +aaaagatatcaaaaagtggttaactagtaaaatgtttatcaggatatcag +caacattttactagttagccactttttgatatctttcacagaaaatgaga +tatataggctcaaagtggacgatccgggtgtcgttctattagaggtttta +cggtaagagatatcacaaatttttcaactaatgaaatCTTTCCCATAtca +tcacaaacattttcttagttgacaggtttttgatatcttttacaggaact +gagataactGAGATCGATGTTGACCCTTTCGTAAAATTCTGTTAGAGTAT +acgacaattgagctcaaaattagcgcctaaatttgaaaatgagcaGCTTA +ACCCctagaaccttccagaaaAGAATGCGGTCAATTTGGACTGGAACCTC +CAAAACTGGATCTAATCGACGAAATCGACGATGACATCAAACAATTTGAA +GTCAATTGGCGATTTATGAAATGTTCAACAATGACCTAGACACACTTTCC +CAGGAGGAATGGATCGTTTTTCGATCGAAAACCTAtctttttgatgaatt +tttgggaaaatggatggaaaaattgaagggaGGCTCGCAGACGCATATGA +GTGTTCGGTTGATGAAGGATGTCGAGCATTTTAAAGAAGTGAGCAGTGCG +CTGAAGTTCTGCAGAGGTGATGTGCTGAGTGCGGATCATTGGCACGAGAT +GTTTCGGTTTTTGGGATTACCAAGGtattgatttttggggttctgggttt +ggggggggggggtcttaATGTTATTTGGTTGCACAGATAGCAGTAACCTA +ACAGGAGGGTACAGAGAAACGAGGCTGCctattttctctgcgtctcctcc +tGGCTTGTTGGGCCCTCCTGATGCAACCACCTGTAACTCAAAAGCTAGAA +TAGCTAGAATAAAATTGTTAACTAACGAAATGTGTATAATATTATGagct +atatttttgtaatttacaaaatttagcTAGCTAAtttttttATAGAAGTC +CTCAAAGTTTGAACTTATTTGTGGCGCGCGCATTTGTTTCTCTGAGCTTC +AAACGCatgtaactcaaaaactaaaataccgtaaaacctctaataaaacg +acacccggatcgtccactttgagcctatatatctcacttgttttgaaaga +tgtcaaaaagtggttaacaagtaaaatgtttatcaggatatcagcaacat +tttactaattagccactttttgatatctttcacagaaaatgagataaatg +ggctcaaagtggacgatccgggtgtcgttctattagaggttttacggtag +ctagcaaaaaactgtcaactagtaaaatgcaTAAAACTTTATGAACTATA +TTTTGcctgttgacaaattttagccagctttcttagtttttgagatacat +gTCCTTAAAGTAAAGGCACACCAGTCTGAAGGTGGAAGCCGCACGCTCTT +GTTTCTCTGCGCTTCGAGCGCGTATGCCGCAAAAGCTAACCGACTTAGCA +TAAAGTTTTTTACTAATAAAATTTGTAGAATTTCATGagctatattttat +tagtttacaaaatttagcTAGCTTCTTTAGTTTTAGAGATACAAGCgctc +aaaaattgtgtttccAGAGGAACCACCATCGAAAAGCTAAAATTCGCGGA +TCTCCTCTCCGTTTCCAAAGCTATCATTGAAAATGCGGACCAGTTGAAAC +AGTTGAACTCTCGTGCTCAAGGAGAAGTTGCCATACGAGATGCGATTCAA +GAATTGACACTATGGGCTGCTCAAACCGAATTCACATTGGCTGATTATAA +ACATTCGAATGGGCAGAacttgaaaatcatcaaagaATGGAAGGAGTCGA +TTAATTCGGTTAGTTTAGTTTGGGGTTCGAACAGCCATAGGATAGTTTCT +TGTTAGCATCCGGAATGAGTGATGACATTGTtcggtttctgtgaatttcc +aaaaattaagaCGCTGTTCAAACAGTTTGACGCTAGAGACACAGCTGAGT +TGTTGAGATTCAAATGTGTGAGAGAATGAGACACAAATGATGGATAGAGT +GAACAGAAGAATGGTCCATTGACCACACAGTCAGAGcaccagaaaaatcg +aaaagaggCATTAGTAAGGGAAAATCAATAGGTATTGTCTGTAGGCACAA +AAGAAGATGTGAGAGCGAGAATCAATCAGTGGTCAAGACGAGCAGAAGAA +TGTGTCCTTGAGAGGTCAAATGTGCTCTAGGGAAACTACTAATATGATGA +CAAAATCTACAAACAAGTTGTTCTAGccaaaaattcttttcttcgaattt +gcggttttaaatttttttttcattttggattAAAGTTGAATCCTTTGAGT +TGGACTTTCCGAGTTAATAACAAGAAAGTTCGTGTTTTAAGCAGCTAGAG +GGGAAATAATAACTTTAAAGACACACGAGAACCTTTTCTAATCGAAAACA +ATGCGGATTGCAAGAAagcgatttttggaatcaactGACTAGAGAAGTGA +CAAGTACaacattagaaaaaaagaaggaaatagGAATTGTATCATTTATT +TCTTTATCACAATACTCGCCATGAAAGTAGAAGATGATAATACTATAGAA +GCTAATCAGAGCTAATTAGCATTAAttagttttgaaataaaacaaaaatt +aaaaatgacttTGAACCACTTCCATTTTGATTGTGTACGgaggaattctt +gaattctgatcTTGTTCGCAGGTAACTTTAAGTTGCAGTTGATGGGGGAG +TGGAATGATGATGAGGCTGGAAAACAagagaaatctcaaaaaccagacGA +CGTGAGCAATTTCTaactgttttcattttcaagttACCAGCAgggttgca +aaaaaaatcacttaaaGAGAACGTTTAGCCTTACCTCTCCTCTACAGCAG +CATTCTCGAAGCGAGCAGCAATAGCTCTCATCGGATCTCCCTCTGTATCA +TACCATCTCACTTGGTTGAATTCATAACATGTCCCGAGTGTCCCCTTTGC +GTTGATCAAGTTCTCTACAATCATTGCATATTCTCCTGGCTGTATCACGT +AGCCAATGGAGATCACAAATTTCTTATTCGGTACTTCACGACACAATGCC +ATAACATCGACTTCCCAGTTGTTGACCAACACCAAAACTCCAGCATCTCG +AACTTTCGGATTTCTACCGTCTCCCAATTTCAAGCCATCCGTCTCGAGAC +GAGTGAACGGGCGGTTTGGATGCCCCAGAATTGTTTCGACTCGTTGTAAA +ACTTCTGACAGGTTTCCGGAAGTTCCAAACCCTTGAACATCAAACTTGAT +GCCTTCTGGAAGACCAATAACTAGACCGTTACTTTCACGCGCCCAGAAGC +CGAGCGATCTGATTTTCGTAACCAATTGACGATTTCCAAGGAATTTGTTG +ATCAGATACTTCTGTGCCTCCCTCAAAGTTCTATCGTGTTTAAAACGTTC +GATGTAGACAGTACCATCTGAAGACTTCCTCGTGAACTGGAAATAGGGTA +CTTTAGAAAACGCATGAAGTTAATACAATTACCTGAATGAACATGTCATA +TGGTAATGGACGGTCATCTCGTTTACATTGAAAACGTAGCACATATAATT +CGTCCTTCTCCAATGCCATTTTCATATGTCGAATTTCTTCATTGATTGCT +TGGAGTCGCACTTCTCGACTAACCCCCtggaatcttcttcttcttctgtc +aaGCTCTTCTGGTTCTAATTCCAGTGGATACTGTGGGAGATTTTCAACCT +CTTCTGGACCATATTGAAGATCCCTTCTCTCTCTTTCCATATCAGCTAGC +ACTTTCTGATCTCTCACCACATTTGCCTCTGCCAATTCAAGATTCATGTC +TAAGTCTGCGGCAGGATCGTAATCTCGAATAAGAATATCCCCAGGAGTTA +GTTCTGGAAGGGAGCGCTTCTCGAATCCAAACCTATCGAAATCGCATTTA +CATCCACCTCTTCGCTGTTCCTCTTTGATTATTTCGGGAGTGGGACCCTC +ACGGGGTTTGCAAATAATACCAAGACGGTATTTGGTGTCGTTTATTTTGA +CGCTcccttcagaaattgagagTTTAGAGATATAAAGTGGAACAGCTTTC +TCGGCAAGACTTATTTTCGGAAGACGTTCGGCAAgtcgaaatctgaaagt +tctcAACGAAATCACTTAATTCTTTTTCGTAAAAGTTACTCACCTAAAAT +TCACCTCTAACTTTTGAAGTACACATTTCAAACAATCATAGGATAGTTTC +TTGTTAGCGTCCGGTATAGCTGATGACATTGTCTGTAAATAGGTTTAATT +CATTTGTAGAGGCTTTCATAATCTACATTTTATTACTAGAAATTGTTCGA +GTTGCAGGAAGGTTATGATACATAAAGACCCTTTACCTCAGATTCGAGGT +ACTCTAGTGAGTTTCGGCTTTTTAACAAAACAATTATTAAAAATGAGTAT +GTTGGgttagaaaaagagaatgagaCACAAATGTTAGTTAAGGCAGACAA +AACAATGGACCATTTACCATAACGCGAGAGTCAGGGCATCGGTGAAAATC +GAAGAGGGTGACTAGCAacggaaaatcaataattgtcTCATGTAGAGACG +TCAGCACAAAGAAGATGTGCGAATGAGAGTCATACAGTGGTCGCTGAAGA +ATGAGCAATGTGTCCTTGAGAGGTTCACATCGGCGGGTTAAACATCTATG +GCCGAAAGGTGGGATAACACTAAAACGTGGGCGTTTTGAACTATCGAATG +CTGAAACTCCTCCAATTTCATAGAGACCGTCTCCAGACGAGCCAAAGGGC +GGTTGGGATGCTCCAGAAGATTTTCGGCTCGTTCCAAAACGTTTGAaaga +tttccaaaagttccaaaCGCTTGAACATCCAACTTGATGCCTTCTGGAAG +GTGAATAACTGGCAATCTCAATTGATTCGGCCAGAATCCGAGCGTTTGAA +CTATAGAGACTAATTGGCGGTTCCCAAGGAACTTGTTGATTAGATATTTT +TATGCCTCGTTCAGACTTTTGTTGTAGGTGACACGTTCGATGTAGACAGT +ACCATTCGGAGACGTCTTCGTGAGCTAAAAACAAACTCTAAAATCACTAA +TTGGTACCGTATTACCTTAAtctcaggtaaacgattctgaattagatctg +acttcattcggaattagatctgtattcgttcgtaaatagaagtggcatga +tctaatacagaatttagctgatctaattccgaacgaacaccgaatgaact +acgaacgaattatatctaattccgaacaggacggcgggatttcggagcat +cgtagcgcgcgcttttcaatttttgttttcttttcaacgccattcacttt +atttataataaaatttattaaaaaagaaaacagaacaagtatgagaaaaa +gaaaaacatagattaaaaTGTAGTTATAGGAAATCGGAACGAAAATGAGG +GGTGTGATACAAATGAATGAATGggatcagcaaaaaagaaaacgatgaga +tcaGCGAGAATAATGGGAACTatgagataagaaaaagtgacaaaatttat +gaaaaaaaatctcaattcgaattcttccgctcgtccatattttcgatttt +gaaaattctcttgtCATAGTTTCCGGTTGTAGATAAGATGGATATTCTTT +ATGAAATGAATGTtgatttaactgaaaaaagaagattttggCTTTGTGAT +GTCGCTTTGGCTTTGTGATATAATCGCTTTGGCTTAGTGATATAATATTT +TGGCTTTGTGATATAATAAACTTACTTGATCCATTTCAATATAATTTCCG +TACTCAAATCTTTGCAAATCCAAATAAATTCATTAGAGCAGTTGTTTTAT +ACaacaaatcccaaatttttgaatcgtttTAATCGGGTCATGACACATTC +GGTTGAGAGCCTGCAATTTCACGCATGTTTCTTTGTCCACCAGACTTTCG +AAAACTAACCTGCTCATGACAAGACACGGCTTCCGAAAGTAAGGCCTTCT +CGACTTGTGTAAATTGAGCTCACTATCAGAGCAATttatcatctcttttt +tcttgtttttttcggtGATCCCTTGCATCGTTTTTACGTAATCCTTCAAg +ctgaaaaaggcaaaaattatCTTACCTGCAGAGTTTTCTCCgaatttaaa +atcttcaaaatcgtcGTATTTTTGTCGATTCATAGATTACTGTCTTCTAT +AGAAGTCGTATAtataaattgaactttgaatattcagctgttcctaaaaa +aattcacctaaaattttgcaaaaacgtgcacaacacattaaaatatgttc +cagaaaatatagtttaaataattgagcgaaaaaaaaggcaaaagttGAGA +GAAATACCCATTTTcctgacgaaaaaaatttaggacaacaaaaaaacaaa +acaattcatcCGCGGCAGCTGAGTCATTGatggcgcatttctcgtggcAA +CTTCGGTATTAGATCTAGTCCatatctaattccgaatgaactcagatcta +attccgaatttcgagttattcgatctaattccgaaagaagccagatctaa +ttccgaatcgtttacctgagaTGAACATTTCGAATGGTGATGAAAGATTA +TCCCTTTTGCACTGATAAAATTTCACTTGTAATTGACTATGTTCTAGGTA +GATTCTGATGTTTCGAAGCTGTGTATCTAGATCGTTTAACTGCTCTTCGC +GGTTCTTCCGGTGACCGGCTCTATTGACCACAACGGATTCGGTGATCTCC +acctcttccttcttcttcttcagttcATCCAAATCGGATTGTAATCTTTT +CACCCATCTCTCCGCACCCTCCAAAGTTTGCCGACGTCTCTCCTTATCCT +CTCGGACTAAAATATCGCCAGAAGTGATTTCCAATCGCTAAGCGTGATCC +TTTAAACCGAATCTATCGATATCAAATTCAACTCCACCTTTTTGGTTCTT +GAGTTTGATTGAAGATGGAGTGAGACCTTCACGAGCTTGACGAATAACGC +CAAGACGGTATTTGGTGTCATTCAATTGGAAGCcggattccaaaaataaa +agtttggAGATGTGAAGTGGGACAGCTTTTTCAGCGAGACGAATAGTTGG +AAGACGTAGGGCCAGTTGGAATCTGAGAAGCAATTTTTTGGAGGGCGGGG +GAGGGGTGGAGGGGGTGGACTTCATCTGAAAAGACTCACCTGAAATTTGG +CTCCAGCTGTTGAAGTACAGATTTCAAGCTATCATAGGACAGTTGTTTAT +CAGCGCTCGGGTAGATGGTGGTGGTGTTCAAAGACATATTTTGGTtctga +aaactaaaagtttcaaaaaaaatatcagcTTAAATGATAGATTCTTTGAA +GTTGATGGATAGAGAGGTTATAGTTAACTGTAGTTCTCTCTAACCcaaat +taataaaatttaaacatttggaattttatatGGTTTTGTAGCTATTATTA +AGTTCCACATTTTGCAGTTCGAATTGACTGTAAATCTTGAATTTGCAAGA +AGCTAGCCAGGAGAGGAAATGAAAAGTTGGGATTCGTCATGCGTTATGGT +GTGGGCAGCAAACTACTCGGACTAGCCATTGTACAAATATCATGTTGTTT +gctgtgaaaatttgggaaaaagagagagagagagagagagagagagagag +agagagagagagagagagagagagagagagagagagagagagagagagag +agagagagaggaaaacgttcagccaatttatctcagtttctgtaaaagat +gtcaaaaaatggtgaactggtaaaatattattgctattatgataaacatt +ttagcagttgacacatttttgatatctttcactggaGACGAGATAACTGG +TCACAAAGTGAAAGCATAGTGGTGGCGCAGCTATAGGCGCCTACCCCGTC +GCCAGTAGCAGCGCacgttttgagctcaattatctcggttactgtaagag +atagcaaaaaatgtttaactaaaaaaatgtggaacattttatgacaaaca +ttttatcagttttctaatttcagttGTCTCTTATAAGagcctagataatt +gagctgttAAAGCAATTATACTATACCAAACAAATTATCTGTCAGTGTAT +CCATATGTTCATGTTTCAGCTCAAAGACAGTCAAGCTCTGCTTCAATCGC +TCAAATCCTCACCCTACTATTCTCAATTCTCGGATAAGACAGCAGTATGG +GAGACGCGTCTTGCCGATTTGGATGTGTTCCTGGCACAAATGAACGAGAT +TCAAAGGAAATGGATTTATCTAGAGCCAATTTTCGGGAGAGGAGCGTTGC +CATCCGAAGCTTCGCGATTCTCGAGAGTGGACTCTGAGTATCGAGCAATT +TTGAATGGTAAGAATTAGAGCCGAACTGCaaaaaagcttcaattttttca +gacgtATCCAAAGATGCTAGATTAGTATCGCTGTGCAGCAGACAGTCGCT +GAAAAAGTCGTTGGAACAAATCGTGGATCAATTGAATCGATGTCAGAAGG +CCTTGAATCAGTTCTTGGAGCAAAAACGAACCGCTTTCCCGCGATTCTAC +TTCATTGGAGACGATGATCTTCTAGAGATCCTTGGCCAATCAACCAATCC +GCAAGTGATTCAAACTCATATGAAGAAGCTGTTCCAGGGGATCAATCGAG +TCGTTTTCTCATCAACCGGAGAGACGATAACATCAATGGTGTCAGCTGAA +GGAGAGACTGTACCTCTGTCGAAAAGTGTTCGAATCGTTCCACAGGTGGA +AACATGGCTCCAAGAGTTGTCGGACGAAATGAGGAGAACGTTGAAGACGT +TGACGGCTCAGGCTGTAGCAGATGGACAAATTTCATTGGGAAAATACCCG +TCGCAAGTTTTGTGTCTCGCTGAGGAGGTCAAGTTTAGTGCCAGTGTTGA +GAATGTGAGTATCTCGAGTAGagtttgaactttgagccagattatatcgg +ttactgtaagagatatccaaaacgtgtcaactgataaaagtcttgtgatt +ttatgataaacattttatcagttgagcactttttgataacttttacaaAA +AGCAAGATAAATTGAATCGAAATTGGGGAGCCTTTAGGTGTGGTGTAGAA +GCATCGtcccccatttttcactttgatcCTGTTTTCAGcgcctgtggaag +atatcaaaaaaatgtcaactaacaaaatttttatcattatatcagtaaca +ttttgctagttgataactttttgatatctcttacagtaaccgaaataACA +TGGCTTAAAGTGGGTGAACATGGTGCAACTGTATTAGACAGTTTGAACGG +TAATTGCGAACGACCGTATCTTCTGATAGCCTTAATACCTTTTGACAAAt +ttaaactaaaaattgagaactaCAAGATGATAATATTTAGAGAGCTGTAG +TTTGTCTAATTCTCTAGCTACATAATCGAGCTACACGCTAGCATCGAATA +TGAGGAAcctccactttgagctcaattatctcggattttataagagatat +caaaaagtaatcaaatgataaagtttttttgatgaactgataaacatttt +attagttgacaaatgtttggtatttctttaaaaaatcgagaaaattgagc +tcaaagtggttGCGCAGCCAACGGAGCTGTTAGCGGCACCAGTATCGGCT +CGTGTTTTGAgattaattatctcaatcactgtaatagatatcaaacatct +gtcaagtgataaaatgttattgataaaatgtttatcatataatcacctaa +attttatcagtagactcatttttgatatctcttatagaaattgaaataat +tggcCCCGAAAATAGTAaactaaatatttttcagatcctcAACTCCTCAT +CCGACCTGTCTTCATTAAAATCGCAACTTCAAGAGAAACTGAAATCTCAT +ACGAACATGAAAGTCGATGATAAAGTGTCGGATCTCAAATTGAAATCACT +GATTCTCGATCTCATCCATCATATCGATGTGGTCGATCAGTTAATGGACA +ATAAGGCGAAAGGAATAAATTGTTGGACTTGGCAAAGGCAATTGAGGTTC +TATTTGGTGAATGGAGGAATCGTGTTGAGACAGGTGAGGGATGGACCTGT +CTGTGTTTAACCTTGTCTGTCTGGCAAAAGATGGGCAAGTGTTGGGCAAA +TACAAAGCTTCAAATTTCAGGTGTCCAGTGAGTTCGAATACACCTACGAG +TATCAAGGAAACTATGCGAAACTTGTGCATACACCGCTGACGGATAAGTG +CTATTTGACTTTGACACAAGGTAtgtggacatctggacatatagataaat +aaataaatttggtttttgggaTTGTCTACCGAAccaaaaattcgttttcc +CGCGAAGCCTGTCATAGTGGGCGCTCTGTTGGTACTGCCAACTTTGACAT +CATTTATCTCGACTCTCAAAAatggtatcaaaaatctgtcaactgataaa +atgttaatgatgacatgataaacattttgttagttgaccactgtttgata +cctcttacgagaacagagataattaggctcacGCGCCGCTACTGGCGCCG +TTGGCTACATCACCACTGTCGATCGAGTTcgagctcatttttctcgattt +ctttaagagatataaaaaaaatagacaactgataaaatgtgtaagataaa +atgatgaaaatttggttagttggccactttttcatatcttttacagtaac +cgagataaattttgACAAAGTTGAGAGCCAATGCTTGCGTCGGCGTGCCG +ACGTCTTAGCTCACAAGCTCAATCTCCTGAGGCTCTTCAATAACGAAACA +AAAGCAATTGAAAGCTTTTTGCTTATGTCCCACTAACTGTCCCAATTCAT +GTCCATTGTGTCCCACCAGCTTTTACATCGAATTCAGACAAATCATATTG +GCTTcctttctaaaaatcttacaGTTTTAAGAATTAGCTGTTTCCAGCTA +TGTACATGGGACTTGGAGGTAATCCATACGGACCTGCTGGTACCGGAAAG +ACAGAATCCGTGAAGGCGTTGGCGGCACTAATGGGTCGTCAGGTGTTGGT +ATTCAATTGTGACGAAGGAATCGATGTGACGTCGATGGGACGAATATTCA +CTGGAATTGTCGAGTGCGGAGCGTGGGGATGTTTCGATGAGTTCAATCGA +TTGGATTCGGTGAGTGTCTATTTCGCAGCCAGACGTTTCGCAACTACTTG +GTTTTTCggcctatttatctcggtccctgtcaaagatatcaaaaagttgt +caactaatgaaatgtttgcgatattatgatgaagtttttatcagtttact +acattttgatatcttgtgtaggagccaagaaaaattagcttacACTTGAC +AGGGTTCTTTTTCAGACTGTCCTTTCCGCGGTTTCAATGCAAATTCAAAC +CATTCAAGGTGCAATAAAATCGCGAGCTGGCTCATGTACCTTTGGAGGCA +AAAATGTTCAAGTCAACCCgaattcggcaattttcgtAACCCTGAACCCG +GCTGGAAAGGGTTATGGAGGACGGCAAAAAATGCCGGATAACTTGAAACA +GTTGTTCCGAGCGGTGGTTATGGGAAAACCAGATAACGAGCTGATTTCGT +CTACGATTTTGTATTCGGAAGGATTTGTGGATGCTACGTCGTTGGCAAGG +AAGATAGTGTCCGGTGaggattttgagctcatatatctcatttcctgtga +aaaatattcaaaagtcgtaaactgacaaaatgtttagcaTATTATTAGAA +Accttttattagttgacaactttttgatatctcttatgggaagtgagata +aattgagctcaaagtgcaggcATAACCAACAGCGACGACCGCGCCGCCAG +TAGCGGCGCATGCTTTGAgattaattatctcagttcctgtgagagatact +aaagatgtgtcaactgaaaaaatgtttataacattattataaacatttta +ccagttaacaactttttgatatctcttataggaagtgagataaatttagc +tcaaaatgtaaGCATAGCCAACATCGCCCACCGCATCACCAGTAACGGTG +CAtgctttgagctccattatctcggttgctttcggagatattgaaaatgt +tcagtctgataaaatgtgtatcacATTATCatttatattttatcagttga +caactttcaaatatctcttacagtaatcaagataaattggtACAAAGTTA +GGGTATCTGCATGATTTTATGCTTTGTAGGTTTCGTTGAGCGTTGAGCTC +TAGACTTtggtttttgatttaaaaagaaattccaaGCTTACAGTATTCCA +ACTATCCCGTCAAATGCTCTCCAAACAACAACACTACGATTGGGGACTCC +GAGCTCTAAAAGTGGTCCTAGGTGGATGTGGAGCTCTTCGACGAGCTCAG +CCGAACAAGAATGAGACGGATTTGGTGGTCCAGGCGCTTCTACTGAACAC +ACTCTCAAAACTGACATTCTCTGATTCGGAAAGATTCAATTCTCTGATAG +ACGACATTTTCGCAAATGTGACGAAGGAGATGACAAAGTTTGAGGAGCTC +GTAGAGCCATTGGGAGTGGCCGCAAAGGAAATAGGAATTAGTTTGGGGGA +AAAACAGATGGAGAAGGTTTTCCAGGTGAGATGGGAATATGGAGATCAAa +ctttgagcgcaattatctagattcctataaaagttatcaaaaaacagtca +actaaaaaaatgtttctaacattatgacaaacatttctTTAGCCGACaga +tctttgatatcttttataggaaccgagataatagagctcaaagttagcgg +tctcaaaaaaaaaaagttaaagttaaagctcaaagttgatgtcAGACAAT +CCCAAGAAAAAGGCGAGGAAGCCCACTAATCCATACGCCTTCTCACTCTA +ACCCTTCAAGCTTCCGGGTTGTGTAGTGGCTAGCGCGCCACACTTTTGCC +CACGAGACTCGAGTTCgagtcccccccccccccccccccccccccgaggC +CAACTACtggtatttttctttttgctacattttataattttcagctctac +gAGCAAATGCGTCAACGTATCGGAGTGGTGGTTGTCGGTGCCGCTGGATC +TGGAAAATCCACAATCTGGAAGGTTCTTCAACGAGCACTGATCCTAACGA +AAAAGCCCCTGAGAGTGACTCAATTCAATCCAAAAGCTGTGAATCGAAAC +AAGTTGTTGGGTAATATGGATATGGACACAAGAGAATGGACAGATGGAAT +TATAACAATGGCAGCGAGAGAAGTGCAAAAAGATACTACAGTACACCATT +GGATTGTGTGTGATGGGGATATTGATCCGGAATGGGTTGAAGCGTTGAAC +TCGGTGTTGGATGATAATCGATTGGTGAGTTGGGGCtagattatctcggt +tactgtaagagatattaaaaagtaatcaattgataaaatgtttatcatga +aatgacctacattttattaattgacaactttttgatatcttttacagtaa +ccgagataattaagctcaaatcAAAAGCATAGTGGTGGCGCAGCCAACGG +CGCCTATTGCGTGCTTTCAcgctaattatctcggttactgtgagagaaat +caaaaagtggtaaactgatagaatgtttatcttaaaggaggcgagacagc +aaaaatttcgggggacagttcgggggacgaaatcccgcctcgcttatgta +gaccatcggtcgtcagccgccttcgcgcccccgtagctcagccggtagtg +gcgctgtacccctgagctgcctgtcatgggttcaacccctcatgggggtt +ctctatgcaaaatatcaggaaaactttttttttgatgtctggcctccttt +aaaattcctaacattttatcagttgacaactttttgatatttattacagg +aaccgagataatcaatatcttctttttcagctcaCAATGCCGTCTGGAGA +GCGAATTCAATTCGGGTCCAACGTGAATTTCCTCTTCGAAACCGACTCTC +TGCAGTTTGCCTCaccagctacagtatcccgaaTGGGAATGATTTACATA +AGGTtagtgaaaataaaaaaaaatctaggtcatgacctagaaaaatctag +gtcacggctcaaaaaaatctaaatcatgacctaaaaaatctaggccataa +cctaaaaaatctaggtcatgacctaacaaaaaaatctagatcatgaccta +gaaaaatctaggtcacggcctggaaaaatctaggtcatgacctaaaaaaa +tctaggtcatgacctaaaaaatctaggccataacctaaaaaatctaggtc +atgacctaacaaaaaatctagatcatgacctagaaaaatctaggtcatga +cctaaagaaatctaggtcatgacctagaaaaattcaggtagtgacctaaa +aaaatctaggtcatggcctagaaaaatatgaaatctaggtcatgacctaa +aaaaatctaggtcgtgacctagatttttaaaaaaatttctcaatttttag +cgaaGAAGACGTGAAACCTCAAGGCATCGTTGCGAGTTGGCTCgcaaaga +attcagaagacgtgcacGCTGAAACAGCCACGTGGCTTGAATCTCACTTC +TGGAGATGTTTCAAATGGGTTCAAACGAAGCAAATACCAGGAATCACCAG +TTTCGCTTTATTGAAAAACGGGCTGACGCATTTGAAATCAGCCAAAACCA +AAACGCATTTTTTGGTGCTCCTATTCAACGGATTCATGCCCTACGTCGTG +CCAGAATCTCGAAATGAATTCGCGAAAAGTGTAGTTTTccaagggattac +tgtagctgaccCCAAGAATATTTGCTACGACGAGCGGGTCGATGGAGTCA +TGACGTATTCAGATGACGTGACACAGAATGTGACGAAGGAAGAAGTCGAG +AGAGAAGATTTGAGACCATTTGTACAAACTGCCGATATTCAGAGATATTC +GGATATtgtgagttttcttttttttggaattttcaaaattttcaaaaatc +aattttttgaaaaaatttctgagattcatCTTTAGCGCATTACATATTCT +GCTTCAGCTCGTTGAGAGCGTTAAAATGAGCCCCACCACGACCTATCTgg +gtcaattttgattttttgttagattactgtagttttcgtggtgggaccca +actTTCAAAGGAatatagtcgtgtttgggctcatttttaaGTCCTTAGCG +AGCTGAatgaaaacaattaaaaattgcTGACGAATATCacaaatttcatg +aatataatgaaaaactgattaaaaaacagaaaaacagaaaaaaaattttt +ctgaaaatcttcaatttttcaaatttagttttttctgaaaattccaattt +caaattatttcaatCTTGCTCAACTTATCGAGAGCTTCAAATTAAGCCTA +AACACCACCTATCTGGgtcgattttgatttttgtggaattactgtagatt +tcgtggtgggacccgaTGTGAACCGAAcctaggcttgtttatactttttt +tgaagctcaaaacaagagaaattcaaaaatatatgtttctttcaaaatga +ggaaatttatactgagttactgtagtttcaaaaaaatattccagatcGGC +TCGTGGCTCCGCCCCGGGAACCGGGAAAGCTTCCTAATCACGGGAACAAC +GGGATGTGGAAAACAACAACTTCTCAAACATTGCTTTCAAAACGATCCAG +AATCTCAGTTGGCCAGTTTATATTGCTCAGCGCAGTCTAGCTCCGCACAC +TTGCTGCAATTGATTCAACAGAACTGTGTGCAGGCTAGTAATCCGACGGG +ACGCGTGTGGAGGCCAAAAGATCGGCCGAATATGATTCTTTTCTTGAAGG +GCATCAATTTACCAGCACCGGATAAGGTATGGTTTTTGTGgtgatttgga +aaaaaaacaagttttcaaaatttcgatgaaaagAAGCTAACTTTGGAGTC +CTGAAAAAGTAGCCCACATTATTtcgatttatctgaaaattacagagtat +actaaacagaaatagagcttcatttttgtaattgacaacttttttgtgca +aacgCGCCCTAGCGAGATACGCCTGCGTTCCTAAGTATCCTCTTCCGCGC +GCCGTCGAAGATGATAGCTACACTttcacgtggcatatctcgtTAGGGCG +CATTTGcacaaaaagttgttaactacaaaaataaagcactatttttgttt +actatacactgaaattttcagataaatcgaAACATTCTGAAGTACTTTTG +TAGCTGGCGCCGCAACCACTGACGCCGCCACCATCTAGCGATGGCTGTGC +TGCGTAGCTCAGCTGGCAGCAACGCGGAACCTCCAACGGCGAGCTCACAA +ACTCAACTTTTTGAGGGGCTTATagaacaagtttttgaaaaaaagtctaT +TAAAATTCCATGTTCCtttaataaaaaagttttcagtacGGCACCAACGA +ACTCCTGGCACTTCTCCAACAACTTCTAACCTATCAAGGATTCTTCGATC +ACAATTTAGAATGGGTTTCAATCGAAAACATTCAATTCGTTGGGTCCATG +AACCCACTCGGCGACGGTGCATCCACAAATATCTCCAATCGCCTCTTCTC +CCTTCTTCGATGTATCTCTCTGAACAACACGGACACTCCCCAGCTGACTT +CTATCTACCGTACCTATCTAACTCCAATTCTTGAAGACGTTGGAgaacga +aattcagaaacactCGCTTCTCGAATGGTTGATGTCTATACCAAGGTTCA +ACAAAGCTTCAAACCCTCTGACAGTATCGTATTCCAATTTTCGCCCAGAG +ACCTTACCAATTGGGTAGTCTCACTTTTGAGACATGAGCTGGATCAAGGC +AAACTGGAAGGAGTGATTTGTTTCGAGGGAAAACGAATATTTGCGGATCG +ACTGCCAACCGAAAACGATAAACAGAAATTTGAGGATATTCTGAGAAATG +TGATTCCAGTGTCGCAAAGTGCAGGTGAGGATTCTACTCTAGAAGAATAG +CGcccaacttcgagctcaattatctcaatccttgtgaaagatatcgaaca +GTGATAAACatataaaatgtttgtgatattatgataaacattttatcagt +tgacacatttttgatatctttcacaggagacGAGATAACTGATCACAAAG +TGCAAGCATCGTATTGGCGCAGCCTACGGCGCCGACCACATTGCCAGAAG +CGGTGTGtgatttgagctcaattatctcagtccTTGTCAACTCaaacagt +tgtcaactgataaaatatttttgcttttatgataaacattttgttagttg +actactttctgatatctttcacaaaaaatgagttaTGTAGGCTCAAAATA +GACGAGAGTATTTACGGGCTGTCTTAAAACCCTAGCCATCAACTTtgacc +aatttatctcggtttctgggaaagttatcaaaaaatagtctattgatgaa +acgtttttgattttatgataaacattttagtagttaaccacattttgata +tctctcacgataaccaagataattaagctcaaagttgacggtcagAGATT +CTACAGTAagatcaaaacatttttcagacaaagtcTACGTCACAACTGGA +TCCGTTGTACCTGGAGAGAGTAACACAGGTCTTCCACTAACTCCGATCAA +CATGAAGGAATACAATCAACTCTTGTTGAAATCAATTAATCGATTCAGTG +AGTTAACTTTAAcacaatttatctcaatttctgtaaaaaatattgaaaag +ttgtcaattaagaaaatgtttgtgatattatgatacacatttcattagtt +gactacatttttgtaacttttacaggaaccaaatTAAACGAACTTAAAGC +CTGCATTGAGgtcaactatctcggttcttataagagatattgaaaatgtg +taaacttataaaatttttaccaTATTATATGCAACATTTTAgcagtggac +aactttttgataacttttacagaaaccgagataaatggttTTCTTTGCAG +CCTTCGAAGTGGCCAACTTCAATTCGCCCCTTACCAGTCAATTATCCTAT +TTCTGTGCATGCCTTGATCGTGTTCTAACCACCCCCGGTGGTCATTTATT +CCTACCCGGACGGACTGGATTTGGACGAAGAGATGGTGTTCGACTAGTTG +CTCATATGCACAATATCCAAGTGTTCTCGCCGGCGGTGACAGCGAATTTC +TCATCGAAACAGTTTGATAATGAAATGAAAGCGGTAAGTGGGTTTTCAGG +TCCCACCAAAGttgttcaaacttttttggattggtctaaaaatttcagag +aatactAACCAGAAATATGGCTTAAATTGTGTAGTTAGCatctttttttg +ggaaaacgcGCTCTAGCGAGATATGTCTGTTTTTCTTAAGACGATCTCCG +CCGTGGATGATAGCTGCAATTCCACTTGCCATAATTCGCTATAGCGCATT +TGCGCAAAAAcgttgttaactacaaaaatgaagctctgtGTTTGTTTaaa +atactctgaaattttcagagtaatcGAGCTGTTGTAAATGTGTACCTGAT +AGACAGGCTTATGTCGTTTTTCACTCTGTCTTCGAGTATCGTAAatactt +gagctcaattatctcggttcctttgagtgatatcaaaaatttgtcaacta +ataaaatgtttatcacaatatccttaatatttttgtagtttgccaaattt +tgatatctcttataggagccgagataattaagctcaaagtgtaagATTAA +GTTTCCAGGCCATCACCCAAGCTATCACGAACAACGAACACGTCGTTCTG +ATTCTTGAAGATCATCAACTTCGGAAAAATGTCTTCCTTCAAGCCATAAA +TTCTTTATTGGCTAGCGGAAATGTGCCCGGATTGTTCACTCAACAAGAAT +TGGATGGGCTAGTGGCGCTGGTGTCTGAAGCAGCCAATCAGGCGTCGTTC +ACAGGGGCATTGCAACAGTTTTTGGCGCATCGtgagtttcagaattgatA +TTTGTTCACCAATTAAAATGGatttaatagaaaaaatgaagagctgcaaa +atgaaaatatttagattactgtatcttgtctgtaaacaaagttacagaca +agTTACAGTCGAACACAGCGACGGCCATGGCGGGGACAGAATTACTTTTT +AATTTGtttctataactttgttcacagaTTACATACAGCTTTgcaaataa +tatcattttgtagcttttgagtttttctataACATCCTTTttatttgatc +aaaaaataacataCCTGAAGAAAGTTTCGAATGGAAAATTACCGTTAACC +ATATAATGGTCCAACCCCTTAACAAACTTTGAACCAGATTATCTCTGTTC +ccttaaaagatatcaaaaagtaatcgactgataaaatgttgctaatatta +tgataaacattttattagttgatcactttttgatatctctcccagaaaat +gagatagaaaggctcaaagttgacggtttggaggGGATCTATTAGAGTTT +CTACGATATGTTATAGTCTGAAACTTCAGGAATCCGAAGCCTGGTCCATG +TCGTGTTGATTCTTGAAGTGGAAGCCAATGATTTCAAACTGAACATCACT +GAAAATCCAGCGATCCTGAAACATTGTAACGTAATCTTTGCTGATCGATT +CGATAAATCTAGCTTGAACGAGGTAagggacatccggacacacagatccc +aaaaacttgaatttcagattcccaaGCTATTAATGGAATCAAAAGGCATC +ACAGCAACCGACTCGATTCTAACTGGATTCCCGGATATTCTCATCAACCT +GCCTGAAAATTTATCCATTCAAACAATTAAATACAGGCAGTTTGTAGAAA +ATTGTTGTCAGCTGTTGGGCTATAAACGGAGTACACTTTCAGCTAGACTT +GATAGGTTGAAGGTATGCATGgtcgctctattgataattaaCAAAAAGTA +AATGTTTAGGGCGGAGTTTCAAAACTGAACGAAGCTCGTGAAGAAGTGgc +gaaaatgcagaaaaaagcTGGCaaaaaaaGTAAGCTACTCGCTGAAAAAC +AGGCGGAAGCTGATGAGGCGTTGAAGGCGATTACGGAGAGTATGAGTgta +agttttgagattttttgattttagattAGGgacttcaaacttttttaggG +AGCAGAAGACCAAAAACTGTCCATGGAGCAGTTGAAAGAGGCGACCGAGA +AGGAAAATGTGGTTATTGAGGAGAAGAAAGCCAAGATAGATGAGCAATTG +AAAGAAGTGCAGCCGTTAATTGatgtaagttttcaaaaaaagttgaaaaa +agaaataaaaagaattGACTTCAAAGGGGTCAAACGTAAGAGTGCCAGAT +TAAAAAGAAAGAGCGTTAGCAAATCAGCCACGCGCACACCAACAGCTCTC +GGCTGCGGCTGTCGTCATTTGGGCGAAAGTTGGCCCCCTTTTGGGCGCTG +TTTGGCCAGATTACGCTTAAGATTTTCCCAGAAGGTGCCCAAACGCCGCT +CAAAAGCTGGCAAAACTTCGCCCAGCTTTCGCCTAAAACCTTCCACCGTT +GCCTTGGGTTCgctttaaatttgtttttctttctttcttggAAGACTAGt +tcaatgagaaaattttatttattcaaaCAATTATGaaaactaatacaaaa +aactgttgaaaaaaagaacatacaaaaaaagaagcttttaaaatttttcg +catCCCCGGCTTGATGTTGCCATCTTTACTTTATCCTTGTCCGTGTCcaa +gtcgatttttcgatcGGGAAGTTGGCTGTAGTtgttatttctgaaaaaat +ttattgattttcaaaaaattgtatcatttatttttcccactgaaaatttG +CTAAGTCTGACACTTAGCAGACTAAAAGGCTTGTGCAGAAttgaatttcg +atatttttcaaactatttctAACGACATTTCGCCTACCATTCCactagaa +atctcaaaagaATTTTAAATGGACTCGATGAGGTCGGATTTTCATTGCCG +ATATACTTAGGGAAATATATCTTCACAAcattacaaacattttaaaagca +ttttctcaatatttttggacgtTTTCGAAAGCTTCAAACCCAGAATATAC +GAACCTTTTGAAGCTTCTTCTGACTTCGCGGATTCTCTGACTTGTCCCTT +CCAAGCGAAGGATTTGCGGCATTCACGAAATTCCGAATCTTGAGTCTAAA +AACGTTATTAATGACTGAATAACATAATTGTTGTTTACCTTACATGCTAT +CAGTGGAAAACTTCTGGAGATGTGCTCAAAgggggggTAGACGAGATAGA +actcagaaaaatgattttctcaGTTCGACGCTGAATGAAAAAGGatttaa +agggggggggggggacatgaaaaaaaaatgttctcgaaattccgtttaaa +gatgcccctcgaggagttgaacttgtgagggcgatgattgagggtgcggc +gccgctaccgactgagccacgcgggcaaagagagagcgcacgcccgattg +catacataaaggcaaggacgacagctgtacgcagcgtgacattaagcgtt +gtacaccgtgacggtagaatgcatactctagctacaaaaaaactacgaaa +aaccTCCTGTccccccctttaattgaaattttctattccACTCACGGTAT +TTGTTCTTCGTcgttttcggtttcaaaaatctaatcatttttggataaaa +atatttagaagtTTGAGCAGGAATTCAGataaaacactgaaaataggaaa +aaataggtgatgcaaaattcgaaatgcaCGCGTCGCTTGCACGCAACGCA +TTCAAAACTCGCCCAGAGTTCGCCGAAGTTCGCCAAACCTGCGTCCGACC +TTCTCCTACACCACCGACTTCCTATTTCCGTCGGGGTTCCCCAAATTTCG +CCAGAGTTCACTTTTATTCTCTACCTgagtgagctcaattatttcgattc +ctatgaaagatttcaaaaagttgtcaactgatggaAAATAGGTGACGtta +tgataaattatttatcagttgacaaatttttgatatctttaaaaagagcc +aagataattgagctcaaaattgacggtttgggagGTCTTCTATTAGGGGA +AATACGGTAGTCCGTTTGGGCTTTGGTCTAGAGATTGTATATCAAATACG +AGTTTTATGTCTTTTTACAGACACCAACAGTTGACTTTTTAGAGGGCATA +CATTTTATGATGTTTTCTCGCAATCAgcatcacttttttcaaccGAGAAA +TTGTCcacaacttttgaaactttaaatttcaagTTCTGAGTATAAATTAT +CAATTATGAATTAAAACTGAGAAAGCAaaatatcttttaaaaaatacatt +caAAATATAATGTCATGTTTTTATTGGCAACTTAACAATTCATTCAAACT +CACACACAATTCATTACATGTAATATTTTTATCAACAGTTTGCCAACAGA +GATTACCATCAAATTTCGCCCAAAAGGCGCCCAAAGTCTGCTCAAAAGAC +GGTGGCGCCCCAACTTCGCCCAAAAGGTGCTCATAGTTCGCTCAAAAGAC +GGCAAGCCCTTAACTATTGCCCAAAAGACAACAGCCGCAGCCGAGCTAGC +ACACCAAAAGGCGTAGATAAGCGCGGGCGTTTCCGCTACTTTTCAGGTGT +GCTTGGCTTCACGAGCTAGGGTAGTCTTTTGGctggaattccgaaatctc +AAATTAAATTTCCAGGAAGCCCGTCGAGCTGTTGGATCGATCAAATCCGA +GTCGCTCAGTGAGATCAGAAGTCTTCGTGCACCTCCTGAAGCCGTGAGAG +ACATTCTACAAGCCGTTTTAGTATTCATGGGTATTCTGGATACGTCTTGG +GAGGCTATGAGAAAGTAAGGAGGACATCCGGGATGTTCAGATACACAGAt +agatttcagattcttgtCGAAAAGCGGGGTGAAGGATGATATAATGAATT +TCGATGCGAATCGAATCACAAGCGAGATTCACAAGAAGGTGACGGCTATT +GTCAAACAAAAGTCTGCATCTTTTGAGGAAGCGGTAGGTGGTagacatct +ggacaaacagattttaattcaaagaaaaatttatagaaCGCTAAACGAGC +ATCGGCAGCGGCTGCACCATTGGCCGCATGGGTAAAGGCGAATTTGGAGT +ACTcaaagattttggaaaagatTTCTcctttggaaaatgaaaagaataaG +CTGATAAAGTGggtttttttaagaaaaaaaggaagaaaaagggtTTTGAG +CCAAGCGCGAAGTCGAACCCGCGACTCTCCGATTGCAAAACAGGCGCGCT +AGCCACTGCGCCACGCGGCAGACAAAGGTTGGAGCACCGCAAGGTGTAGA +GGAGGGTGGCGGATTTTGCGTTTTTCCAGGAGTGGGAGAGGGTCGCCTCa +tatgattaaaaaaaattccagaaatctcaaaaaagctgaaaaacaaatgg +aaaatctatccaaaGGCTTGCAAAGTGTTGACGAAGTGGTTGGGGAGTTG +AAACGGAAATTCGAAGTGCTGATGAAAGAAGCGACGCAGATAAAAGTGGA +TTTGGATCGAGAACAAGACACGATTCGGATAGCTGGCACACTTGTTGAGA +GTCTTTCCGGCGAGTTTGAGAGATGGAAAGTGCAAATTGAGACATTGGTA +GAGGAGCAGTCAAAGGTAAGGGTCCTGTAGGCAGAGAGATACGAATTAAA +ACAACTATATGTGGCTTTCTAAACAGTCAACTTCGaccttatttatctcg +gttcctgtgaaagatatcaaaaattggtcaattgtTAGAATACTTTCCTT +GTTATgctgaacattttattagttgaccactttttgatatcttttacagt +aaccgagataaatcagattttccaaaaggTTCCAATAGTCCGTCGGCCGT +CCGTCAACGACCCGTCCTTTGGTTTTCAGGCCATAAAAGAtccaaaatca +atttcaaacgTATTTTCAGATAGAAATGTGCTCTCTTATCACCTCTGCGT +TCCTCACCTATCTTGGTGGTTGCTcagaaaaagatagaaaatcACTACTA +AAATCCATGTGTAAAACATTCAATATGCCCTCTGGCTTCAACCCTCTCTC +CTTTGCCAGCCTGGAAACCGAGCAACTAAACTGGAAAACCAAAGGACTAC +CAGCAGATCAACTCTCCCTAGAAAACGGATCGATAATGTTCAATTCACAG +CATGTGCCTTTAATCATCGATCCATCTGGACAAGTGTCAACGTTCCTGGC +CAAGTTTCTGGATAAATCTGAAACATTCAAAGCTGCTCAACCGGACCTTA +TGACTCAAATCGAGTTGGCGATTCGATTTGGAAAAACTATAATCGTAGAA +GATGTGGTGGAGTTCGATGCAGCACTGATTCCGATTCTAAGAAGGGATTT +ATCAAGTCAGGGACCACGTCAAGTCATCTCCTTTGGTGGAAAATCGATTG +ACTATAACtccgatttcaaaatctttatttGCACCAGAGACGATAAAGTT +GAAATAAGACCCAATGCATCTGCCCAATTGAATATTGTGAACTTTACAAC +TACGATAAGTGCTCTCTCTGCTCAGCTTCTCGACGTCGCTATCCATCTTG +AAAAGCCGGAGCTAGAAGAGCGATCATCGAGTCTTCTCCGAGACgctgag +ctcaaaaaattggagcttgAGGGTTTGGAGCAGTTGTTGCTCCAACAGTT +GGCTACGTCACAGGGAAATCTTCTGGAGAACACTGCACTTTTGGATTCGT +TGAACAAGTCGAAAGAGAGTGCCGAGATTATTAGTAAGAGTATTGTGGAG +AGTGAGCAATTGCACAAGGAATTGACTACGGTAGGTCttgatatcgaaaa +gttgtcaactgataaagaaCTTGTCGTAGTTTGTGTCACATTTTAGTAGT +Tggtaaatttttgatatctcttacagtaaccgagataattgagctcaatt +atctcggttcctataagagatattaaaaagatctcaactaataaaatatt +tctcatgttatgataaatattttatcagttgacagatttttgatatctct +tacagtaaccgttTTACAGCAAAAAGAAATCTATGTGCCGTTGAGTCAAT +TCACTTCAAGCCTTTTCTTCTCGTTCTCCAATCTACAGTACTACAATTCA +ATGTACAATTATAGTGTCAACACGATAATGaagctttttgaaaagacTAT +CAAGTCGTGTGAGGTAAGAATTCTGTGCACTTTTGCGTGATGGTGTACAA +CGACTACGGTATCTCGATCGGCCGCCAAAGAGTCGACTGCTACCCCAACT +TTGAAGCCCCACGAAAGTAATCCAAAAAgcttcgatttgtctgaaaattt +cagtgtatactaaacaaaaatcgagcttcattttcgtagttgacaacttt +tttgtgcaaacgCGCCCTAGCGAGATATGACGCAAAGAAGCGTCGCGGTG +GCCCACGGCGCCGCCGCCACCTCTACctcccttcaattagaggttAGCCG +CCTTCTTTGCGCCGTATCTCGCTAGGGCGcgtttgcacaaaaaagttgtc +aactacaaaattaaagttcTATTTTCGTTCAGTATACTTACCAAATTTCA +gagcaattgaaaaatgttggactacttttgtagggcttcaaagttggcaa +ttttcaaatttttgaaaaaaaagaccaataaaaataaggaatttttGTTC +TAGGACAAAAGCTCAACTCGTGTAGAAAGCCTTGCTCGTCAAATGCAGCT +TACCGTATTCTATCATATCTCTCGTGGAATCTTCCGTCAGGACCGTTTGA +TGTTCGCTGTCGCCTTCATAAATGCAACACAACCGAAAATGTTTCAACCA +AAAGAGTGGGAACTGTTCACAGGTATGTTATGGTATGAAATAATGTGGAT +AACTAAGTTCGGCTTGaaataagcttcaaaatgagcccaaacaagCCTAG +GTTTGCTTCGAAtcgaattactgtagttttcgtggtgggacacaattttg +agcaaaaatattcgtgtttaggctcattttggagCTCGAAATGAGACAAG +CTTAAATTAAAAcctatattttaaaatttagctTGTTTagtgtttcaaaa +tgagcctaaacaagCCTAGGTTTAGTTCATATTGGCTCCCACCAcaaaga +ctacagtaatcaaactaAAAAGCAGAGTTGACCTAGATAAGTCTAGATAA +GAAGCTCTCAGCAAGCTAAATTTTGTTGATATGGTCAAACTGATGTTCCA +GGAGTTGTAAAATATCTTTAAACAGAATTAGGTTTGCTTGAAAtcagact +actgtagttttcgtggtgggacccgaaCCAAGGCTTGCTTCAGGCTCATT +TTGTAGCTTTAAACAAGCTTTTACTTACCAAACTAAGCTTCCAGGGCTTC +TTAAGAGCTTAAAAAGGGGGTATCTTGAaattgaattactgtagtacAAG +GTTAACTTaaaattggattactgtagtttaggcTACCCAAAGTCTCCTTA +CTTCTAAAGTCCAACCTTATTATTACAGGGGTTCTCGTAGACGAATCAAC +GGATCTTAGTGGCATCCGAGTGTCCTGGATTGCTCCAGATCGTCTTCCAT +CTCTAGCCAGAATCCGAAACCATCTTCCGAGTCTCTTCAATAATTTCCAA +ATTGGCGACGACGCGACGTGGAGCGAATTCGCAAAGATGCTCCAGTGCGA +AACGGCGTTTCCGAGGAATGTTGAAGTGAAAATGACACATTTCCAGAAGG +TTCTTTTCATACAGGCCGCAAGACCAGAACGGTTGTATAATTGTTTGATG +GATTTTGTGCTCAAGACGTTGAGTGGGTGATTTTGGAGAatcagattgct +cagcttccagattttcagtaatttctgattctttaaatttccagacatcC +CCTCAATCAATCCACCAGCTTTTGAACTCCGTCACATCTTCTCAGAATCC +GAATCCTCCGAACCCATCCTCTTTATCCTTGCCGATGGAGCAGACCCATC +CCAGGAGCTCGCGGAGCTCGCCAGCGCTCTTAAAGTACCGTACCACTCGA +TTTCCATGGGACAGGGACAGGAGCAAGCCGCGTATGAAGCAATTCGGAAC +TCGGCCGCTAATGGGGAATGGTTGTGTTTGAACAATTTACATTTGATGCT +TCAAGCGGTCCCGTCGATTTTTAAGGTAggctttttgaaaacgttttagG +AGCCCGTTTAGCTTGCTGAAGCCTTcaaaacatatatttttgaatttagc +tcgttaagagcttcaaaatgagcctaaagaCGACTTAtctaggtcaattt +tgaatttttgttggattactgtagttttcgtggagGGGCCCGATGGGAAC +CAAAACTAGTCTTGtttaaactcattttgaagctccaaacaagagaaact +caaaaatatacatttcTTTCCAAATGGTGTAGTTTCCactgagttacggt +agtttcaaactaaaaaaaaaagattttgagtttcaaactACTGTCACTCG +GGGAGAAATTTACTATTCTCAAagaaacaaacatttttgaatttctcatg +cttggagcttcaaaatgaacctaaACAAGCCTAGGTTTGGCTCACAtcgg +gtcccaccacgaaaactactgTGATCcagaaattacagaaatttaagatt +tttttgaaaaatattcgaaaacgattttttcgtcataattcaggtatttt +caattttcttcatttgaattttaacaattcttattcaGCTTGATAAATGC +TTTGAAACAAGCCTAAACACgtccatatttttttttaaattgcaaAATAa +atgggtcccaccacgaaacctacagtaatccaaaaaaaaatcaaaactag +tCTAGAcaggtcgtgtttaggctcatttagAAGCTCATCCcaagccaaat +tcaaaaatacaattttcttctgaaataatagaattttcactgttacggta +gtttcaaattgaacgacagtttttttgaatggaaaactaccgtaactcac +tGAAAATTCTGCCAATTTGAAGGaaacatatatttttgaatttggcttgt +ttagagcttcaaaatgagtataaacaagcctttgttcgggtcccaccacg +aaaactacagtaatcccaaatcAAGCAATCCtagccgtgtttaggctcat +tttgaagctcattcCATGCCCAATCCAACTCATAACATAATTTTCCAGCA +CCTTTCCCTCACAACGCCCCACGAGAACTTCCGCCTATGGTTGACTACAG +AAGCAGACGCCCGTTTCCCCTCAATGATGCTCCAGCAATCgctaaaaatc +acatttgaACCGCCGCCAGGCGTCCGGAACAACCTGCTGCGGACCTATAT +ACAAATCGATCGAAATGGGCGGAGTGTTGTGACGTGTCAATCGATATTTG +TGTTAGCTTGGCTTCATGCCCTTCTTCAGGAGAGACGAACTTTCATTCCA +CAGGGATGGACCAAATTTTATGAGTTCTCAGCTAGTGATGTGAGAGTTGC +CAAGTCGTTTGTAGAGCAATTGACTGAGAATAGTGAGTGGCtttcaattt +gaagaatttcagaaatttttttttgaatttcgaatttctgaatttctgaa +tttctgaattttagaattttagaattttagaatttctgaattttagaatt +ttagaattttagaattttagaattttagaattttagaattttagaatttt +agaattttagaattttagaattttagaattttagaattttagaattttag +aattttagaattttagaattttagaattttagaattttagaattttagaa +ttttagaattttagaattttagaattttagaattttagaattttagaatt +ttagaattttagaattttagaattttagaattttagaatttctgaatttt +aaaatttttgaatttcagagtttctgaatttcagagtttaataggaaact +gaaaatcctaaaaatcgtcaaaaatctaaaaatatgaaaagactaaaaaa +ctgaaatctcaaaaatcttaaactctagaaatctgaaaaagtttcttttt +ttcttaatttcaggtttttcagattttctagaaaatttgaaaatctggat +gaaaatcctaaaaattctgaaaaatgtgttttttttcgaattttgaaatt +ttcaggttttctcagaatctcaaaatctgagaatctttAAATAtccaaga +atctgaaatcaaTTCTATtgtcaaattcgaaaatcttaagaaccctaaaa +atctgaaaatcttttaaaatttcagaatttcagaatctaaaattctaaaa +ttccaaataatcagataccgtaatccctgtaatagaagggctctctaact +ttcaactttgagtcaaattATCTCGCTTACTgtcgaagatataaaaaagt +tgtcaactgataaattgtttatcacaatatcacaaacattttatcagttg 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+AGTTGCATTCTATGCCGCTATTTCCATAGTTCgggtttttaggccaccat +atcctaatttgggtttctaggccccattttatattaggttggcgggaaag +tctttgtcactttttcaatagtttatttctcaaagaaaaaataaccgaat +aattaattatattgtccatcattatcaacaacatgtctccaacgttccct +caatttatggattccattgcggtagaatccagccgggcgtgaggcaaagt +attgtttgagtgccgcttcgaccgctccacgggaattgaagcttcttcct +tcgaaggcacgtgtcatatcgccaaataaccaatagtcggaaggagcaag +atcaggagaatacggggggtgagggagaacattccatccatatcccatca +gctcctgcttcacttgtttcgaaacatgtgggcgagcgttatcatgttga +tagtacactttcttgtctttcagggccgaacggtcgactgctttcttgag +gtttcgtagttgagtagtgtagaggtctccagttattgttttgccctcgg +gcagaagttcccagtagatggggccgtccactccccaccacacagagagc +ataacttttttcggatgaaggtcgggtttggggacatcctgtgggctctc +tccttctccaacccactgggatttcctgtggtgattatcgtagaagaccc +acttctcatctccggttattagccggtccagccatcgatcgcccgcgtgg +agagtgagaagagtaatcgaatcgtcgactcggcggtcaaggttggcttg +agtcaggtgatgaggtatgaatcgaccaaaaagttttctcattccaagag +acttcaaaccttcaaggactgtgctatggtgaactccgaatgtgacagct +agttcacggctagattgaaatggatccgattgcaatgcgtgcttcagctt 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+AGCTGCCAAAAAATACATCAAAATCGTCGGATCCAATCAATGAGGTCTTG +TGTTTGGAGACGATAAACGCACTGATTTTGATCAGAAACCTCCATAAAAG +CATTGGAGACGTCGCCAAATCCATGAAGAATCCATCGTTGGCATCTGGAG +TCACTCAGAAGACGATCCAATCGTTGATCTTTCAACAGACACCTGATGAA +TGGGATCGATTGTGGGCGGGGCCAACGGACCCCGCGGATTTTTTGAACGC +GGTGGTGAAGAAGACGCGGGGAACGATGCAGGTggggggttttgggattt +tctaggggaaattttgaatttttgaaaatttgaaaaaaataagaaaaatt +aatttttggctcaaaaatttgaaaatttaaaaactcaaaaaaaattgaaa +aaatttttttcaagtcttttaatttttgattttcagacaaatttttcaaa +ttcaaaaaaacaatttttttggaaattttgaaatttcgattttaggatca +aaattggattttccggtttttcggctcgaaaatttgaatttttcgaatta +aaatcgatttttttatattaaaaaaagggcttttttcaaaaaaaaaaata +tttctttgaaaatttgaatttttggctccaaatttgaaaattttaaactc +aaaaaaattgaaaaaaattgtgattttaagaactttttttagattttttt +ttgacaagattcgaaaaatattttttgcctcgaaaattatttttttcaaa +atttcgaaaattttgaattttttgctattttccgactttcaaaaatttcg +aattttttaaaatttttcagatttttttgaacttttaaaatttcagattt +tttttgaattttttgaaattttgatttttttgcagcTCTACGAAGCCTCC +AAATCCTCGTCGATCCTCTCCTCTCccatcgatttttcggatctCTTCTA +TCCGAACATCTTCTTGAATGCATTGAGACAAACCACGTCTCGACAACTCC +AAATTCCGTTGGATCAACTGATTCTCTCTTCCGCCTGGACACCATCCCAA +CTTCCACCGAAACAGTGTGTCCAGGTGCAGGGTCTTCTACTCCAAGGTGC +CACTTTCGATTCGTTCCTCCGTGAGACTACCGTATCCAGTGCTGCCTACG +TACAGGCGCCGATCCTCTACTTGGCATGGACTTCTGACAGCTCTTCGACG +ATCACTGGCGAGCAAATCCAGGTGCCGCTGTACAATTCCAGTGAGCGTTC +CGACTTGATCACCGCTGTCAACATGCCGTGTCGTGGTGCCGATCAATGGA +ACATCGCAGCTGTTGCCCTATTTCTgcgataacaaaaaaaaagatttttt +aacaactaaaaatacagcttaaaattaaataaaatgtattgtgcgtttaa +aagtgaataaaaaatcatgaaaaaagatCACTAGTTATCATTACCAGCTA +gcagatcgaaaaaaaaggaaaaaaattattgtacATGAAAGCGATAATAA +ATGAagcgaaaaataaaacaatttagtTTTCAGTGTCTTCCTCCTCATCG +ATCGGCGCTTCTCTCCGCTTCTGAATCGCGTTTGGACTTGGGAAGAAGTT +CGTCGAGTCCAGGAGGCTGTCCCTTCTCACGAACGCCGTCACACGACGCT +TCTTTTTCGCGAGCTCTCCGTCGCTTCCGTCCTCAGCGTCCTCCTCCATT +CCGAGCAATGTCTCCGGCTCCACGGGTTTCACGAGCTTCTCACTGGCTGG +GTACTCGGGAATGATTCTCGGCGGTACATTGTTCGATGGGTCGACGAATG +TCATTTTGACTGCATTGATGGCTCCGGTGGCCTCTTCAGTGACGATGTGC +GTGGCTTCAGCGAACATTGTGAAGAGTGACATCTggaaattatcattttt +aagTGTATACAGTTTgatagagcgcatttacatATTTTTAGCTGGGAAAT +ACCGCTACACATGACAGTTCTTTCGCAAACGGTGTCAGTTCAATTCCCCG +TGCACATCCCCAAAACTTCTTTTAACTTACCGTTCTTTCTAACGACTCCT +GGACCnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnaaaaaagttgtcaactgataaattgtttatcacaatatcacaaac +attttatcagttgacaaattctcgatatcttttaaaggagccgagataat +taagctcaaacttgacaatgtgggggcccttctattacaggtttcacgat +attttgaaattacctcaaaaattttttttcaaaattcaaaattctcatgg +cctaacttttcactaaaaccccattttctcttccagaatCCGATTGGGAA +TTCGTCCgtggaattctgaagttcgtGATCTACGGCGGTCGAATCGAGAA +TGATTTCGATGCGAAAGTTCTCGAATCCtatttaaatattttgttttccg +ATGACAAAATTAATGGGCGCACTGGCCAGCAATTGGTGAAAGGAATCGAT +ATTCCAGCGAGTACTAATGTTCAGGTACgatctcaatggagcgcacatgc +taaattttttgaaaattattcaaaaaattatccacGGAGCGCgctttcat +tcttttttctgtcgagaaaaaatcgatgaaaattttgCCGCACCGCTCAA +CCGCGCTCCACCGAACAAACAACGAATGGAGCGCGTTAattgtcaataga +gcgcactttctcaataaaaaattcaaatttcttcaggAATACATCTCGCA +CATCTCAAAGACGGTCCCATCCGTCGACGAACCATTCCTCTTTGGTCTTC +CcgaaaatatcaaatattCATGGCAAATCGTAGAAGCCGATCGAACGATT +TCATCGATACGAACACTAGGttcgtttgaaaatcaatatggtggcctaga +aaatctctaggccaccaatccCAAAACTATTAcacgtggcctagaaaccc +aagtTTAAAGTTTCTTGATGTAGAGTATCcataaatggcctagaaaccca +aatttgaaCCTTTTGgactagaaatccaaaactaggaaatagtggcctag +aaacccaaactTGGGAGatgctggcctagaaacccgagTTTGGTAGTGGC +CTAGAACCATGCAAAGTTGCATTCTATGCCGCTATTTCCATAGTTCgggt +ttttaggccaccatatcctaatttgggtttctaggccccattttatatta +ggttggcgggaaagtctttgtcactttttcaatagtttatttctcaaaga +aaaaataaccgaataattaattatattgtccatcattatcaacaacatgt +ctccaacgttccctcaatttatggattccattgcggtagaatccagccgg +gcgtgaggcaaagtattgtttgagtgccgcttcgaccgctccacgggaat +tgaagcttcttccttcgaaggcacgtgtcatatcgccaaataaccaatag +tcggaaggagcaagatcaggagaatacggggggtgagggagaacattcca +tccatatcccatcagctcctgcttcacttgtttcgaaacatgtgggcgag +cgttatcatgttgatagtacactttcttgtctttcagggccgaacggtcg +actgctttcttgaggtttcgtagttgagtagtgtagaggtctccagttat +tgttttgccctcgggcagaagttcccagtagatggggccgtccactcccc +accacacagagagcataacttttttcggatgaaggtcgggtttggggaca +tcctgtgggctctctccttctccaacccactgggatttcctgtggtgatt +atcgtagaagacccacttctcatctccggttattagccggtccagccatc +gatcgcccgcgtggagagtgagaagagtaatcgaatcgtcgactcggcgg +tcaaggttggcttgagtcaggtgatgaggtatgaatcgaccaaaaagttt +tctcattccaagagacttcaaaccttcaaggactgtgctatggtgaactc +cgaatgtgacagctagttcacggctagattgaaatggatccgattgcaat +gcgtgcttcagcttgtccaaatccaactcacggggtctcccagagcgatc +cttttcatcgagcgagaagtcatctttttcgaaacgatggaaccaattgc +gaatagtattgtagtgaggggcatgtgtgttgtacacattcttcaagaaa +gtttccgaatccttcatcgtggtgtgagataggaagaggtaaatcaaaac +atgtctgatgtgaatagcagtgggaacaaacatatcgtttcaattacaga +tgaggagcagggaaggagatggggacttgtttatatggaaggttcttatc +accttgttattcactaaagtcgatatcatacacagcctccatatacgaga +acagtgattaaacaaacagagtgacaaagactttcccgccaacctaataa +tataagatttctaggccaccaaatctCAGCTTTCCAGAATTCTAGGTCAT +CGATCAAAAACCGTGtcctagaattccaaatttcgaatcgaatgacctag +aaacacaattcaaaaattctgaaccagaattctggatttctaggccacca +tgttaaaatctgggattcctaggccaccatttcctatttttcgatttctg +ggCCACCATCttcaaatttggttttctaggtcataataTAAgtcttctag +gccaccaaatctCAATTTTGGAGATAGAAACCCAAATGTTGGAGGTAGTG +CCCTAGGAAACCAATATTTTGGGTTCCTAGGCCATCGATCaaaaaaaCGT +Gccctagattttcaaatttcgaatcgcatggcctagaaacacaattctaa +aattctaaaccagaattttggatttctaggccacgcccactaAATCTTTT +CAGCACTGGGCGACTCGAAAAATGCGCTCTCTTCGAATAACACCTCCGAA +TCGATATCCCAAATAATTTCGCTATGGAGAAAATTGTGTCAATCGGATGA +TCTCCCaaaaaaaGAGCTGCCAAAAAATACATCAAAATCGTCGGATCCAA +TCAATGAGGTCTTGTGTTTGGAGACGATAAACGCACTGATTTTGATCAGA +AACCTCCATAAAAGCATTGGAGACGTCGCCAAATCCATGAAGAATCCATC +GTTGGCATCTGGAGTCACTCAGAAGACGATCCAATCGTTGATCTTTCAAC +AGACACCTGATGAATGGGATCGATTGTGGGCGGGGCCAACGGACCCCGCG +GATTTTTTGAACGCGGTGGTGAAGAAGACGCGGGGAACGATGCAGGTggg +gggttttgggattttctaggggaaattttgaatttttgaaaatttgaaaa +aaataagaaaaattaatttttggctcaaaaatttgaaaatttaaaaactc +aaaaaaaattgaaaaaatttttttcaagtcttttaatttttgattttcag +acaaatttttcaaattcaaaaaaacaatttttttggaaattttgaaattt +cgattttaggatcaaaattggattttccggtttttcggctcgaaaatttg +aatttttcgaattaaaatcgatttttttatattaaaaaaagggctttttt +caaaaaaaaaaatatttctttgaaaatttgaatttttggctccaaatttg +aaaattttaaactcaaaaaaattgaaaaaaattgtgattttaagaacttt +ttttagatttttttttgacaagattcgaaaaatattttttgcctcgaaaa +ttatttttttcaaaatttcgaaaattttgaattttttgctattttccgac +tttcaaaaatttcgaattttttaaaatttttcagatttttttgaactttt +aaaatttcagattttttttgaattttttgaaattttgatttttttgcagc +TCTACGAAGCCTCCAAATCCTCGTCGATCCTCTCCTCTCccatcgatttt +tcggatctCTTCTATCCGAACATCTTCTTGAATGCATTGAGACAAACCAC +GTCTCGACAACTCCAAATTCCGTTGGATCAACTGATTCTCTCTTCCGCCT +GGACACCATCCCAACTTCCACCGAAACAGTGTGTCCAGGTGCAGGGTCTT +CTACTCCAAGGTGCCACTTTCGATTCGTTCCTCCGTGAGACTACCGTATC +CAGTGCTGCCTACGTACAGGCGCCGATCCTCTACTTGGCATGGACTTCTG +ACAGCTCTTCGACGATCACTGGCGAGCAAATCCAGGTGCCGCTGTACAAT +TCCAGTGAGCGTTCCGACTTGATCACCGCTGTCAACATGCCGTGTCGTGG +TGCCGATCAATGGAACATCGCAGCTGTTGCCCTATTTCTgcgataacaaa +aaaaaagattttttaacaactaaaaatacagcttaaaattaaataaaatg +tattgtgcgtttaaaagtgaataaaaaatcatgaaaaaagatCACTAGTT +ATCATTACCAGCTAgcagatcgaaaaaaaaggaaaaaaattattgtacAT +GAAAGCGATAATAAATGAagcgaaaaataaaacaatttagtTTTCAGTGT +CTTCCTCCTCATCGATCGGCGCTTCTCTCCGCTTCTGAATCGCGTTTGGA +CTTGGGAAGAAGTTCGTCGAGTCCAGGAGGCTGTCCCTTCTCACGAACGC +CGTCACACGACGCTTCTTTTTCGCGAGCTCTCCGTCGCTTCCGTCCTCAG +CGTCCTCCTCCATTCCGAGCAATGTCTCCGGCTCCACGGGTTTCACGAGC +TTCTCACTGGCTGGGTACTCGGGAATGATTCTCGGCGGTACATTGTTCGA +TGGGTCGACGAATGTCATTTTGACTGCATTGATGGCTCCGGTGGCCTCTT +CAGTGACGATGTGCGTGGCTTCAGCGAACATTGTGAAGAGTGACATCTgg +aaattatcatttttaagTGTATACAGTTTgatagagcgcatttacatATT +TTTAGCTGGGAAATACCGCTACACATGACAGTTCTTTCGCAAACGGTGTC +AGTTCAATTCCCCGTGCACATCCCCAAAACTTCTTTTAACTTACCGTTCT +TTCTAACGACTCCTGGACCTTCGTCTGGAGGCTTTCGCCAGTCGTTCGGC +ATGTTTCACTCGTTGTCGAGTATCTGCCAAGTGCAGCCTCAACTTGAGCA +GTCGTCTCCTCACGAATCGCATTGGCCTTCTCCAGAAGCGTGCTTGTCAC +CTTCTTCACCTCTCGGTCCTTCTCCACAGCTCTTTCTCTTGCCTCCTTAA +CCGCGTTCTCCATATCCATATCGATATCATCGAGATCCCCACGTGCACTG +TCTTCAACTTCCTTGACATCGCAACACTCCTCGATGACGTCTTCAACCGA +TTGGATGACATTTTCAGCAGCGTTGATTGTCGAGAGAATGGATTCTTGAG +TGTTCTGATCACCAATGAGTTGTCTGAAAACCGGGGAACTTCGAATGAGA +TTTTCTAATTGTTACAACTTACCTCTCATGATTCTCCTCTGCTTTCACTG +ACAACTGTTCCACTTGCTGCATCAACATCTTCAGAGTCTCCGCCATCCCC +GAGCACGTCTTCTTGACTTCAGCGACGTTTTCGTCGCTCTGCTGAACTCT +CTTCTCGAAGCTATCCGAAGTGGTGTTCCGAATTTCAGTGAGCAACGGTC +TCACATCATTGGCAAATGCAGCGACTTGTCGTTTGATCTCTGCAAGCTTC +TCCGTCAGCTGCTTACTCAATTCCTCTGATCTCGTTGCGTGAGCCTTGTA +GTACTCAACGCACGTCTTCAGAACAGCATCCCATTGCTCACGATTGTCGT +TAGACAGCGAATTGATGGTGTTGGCCGCATTCTCCTCGATCTCGGTAGTC +TGTTGGAATACATTCATGAGTGATGTCTGGATTTCCTTAGAACTTTGGTC +GATGCTGTCCGCAACAGATCCAAACGTCTTCACATGTGGCGTCACTTCAT +GCACGAACTCTTCTGATGCCATTCTCCCATCATTGGCGAACGCTTCTGCT +TGGAGTGAAGTCTTTTCGATGAAGGAGGTCATCTGGAATGATAGAAGCTT +TAGTTTTCCAAATTACCAACAAGcttcttcaaaaactcaccttcCGCCTG +AATGCTTCGAAAATATCCTTATTCCGATCGTCAGCAGCTCCCATGTCGTC +CACTTTTCTCCAAAACGCCGCAATGTCGGTCGTCAACTCATCGGCAGCTT +CTCGAGATTGCAATAGCTGATCAAATGACTTCAACGCGTTGGTGTGCATC +ACTCCGATCGCTTCAATGTTCTTATTGAGAACGTCGTTCGTTTCCGCGAG +CTCCACCACTTTCTCAGCATACTCGCGATGACTTTCTCTTAGACGGCTCT +CCAGCTCTCCCTTCCGCTCATACAGCTGCTTGTACTGATCATCCATGTAC +AACAGATCCTCTGTGTATCGTCGAAGTCTGTCCACTGCGCTATCCAACTT +CTGTTCGAGCTCATTCACCTTTTCAGTGTTGCGTTGGAATTCCTCGTGCG +ATTCTTCACTGATGATGACTCCGTTCTTCTCGCGAGCCGCTCTCAAGTCC +CGACGCAACTTCTCAATCTCATCCGAGTACTCTTTGAGAATCGTCTTCTT +TGACACCTTCGTATTGCACACTGGCTTATTCTTGATGTTCGCTGCTCTCA +TGGCGTACTCCAGTGTGCTCTGACTCtcctcaaaatttgagctcgATGGT +GAGAGAGTTGCGATGAGTGAAGTGATGGTGGATCCTCCCAAACTGTCCTG +TAGAAGTCTTGTGAGCTTCGACTCTCTGTATGGGACGTGTTGAGCATTGG +TGGTGAGCGATCGGATGACTCTTCCAAGTGTCAAAAGTGACTGATTGATC +GATCCAGCTTCCTTGGCACGATTCCCTTGAGCTCCTGATCGTCCGATGTT +TTCAGATCCAGCCAAATCGACGAGGTTCAGCTTTCCTTGCTTCACCAACT +CCTCTCCAGTGTTCGTGTTTTCTCTTACAACCACATTGACCATGAACAGA +CTGTGAGATCTGCTGCTGTTCATGTTCATTAGTGTGGCTGCCGTCTTCCG +CTTCTCGGCTCCAGTTTTCAGCAATTTGAAGACGTCTGAACGACTTCTGA +CCGGCACTTCTTCGACTCCCGACACAATCACTCCCTTTTTATGGGGATCG +TCAAAAATGCGAAGACGTTCACGGTCTTCGTCGTCCGAAGATGCCAGAAG +ATCCAAGAGCTCTTCGTTGTACAATTCCACGTAGCTGACTCGCAACGAGT +ATTCCTCACATTTTGATGATtccaacttttcgaaaatgtccTCAACAGCT +CGTGGAATAATCCCAGTGGTCGGATCGTCTTGTGAGCTCTTGGCATCCGT +ACGCCCTCCTTCCATCGTGAACGTCTTTCCCGTTCCAGTTTGTCCGTAAC +TGAAAGAATGGATATTACTggttgaattctgaaaaaatcttacGCGAAAA +CTGTGCAGTTGAATCCAGCGATCACTTTCTTGATTTGAGGAGACACCAAG +TCGGCGTAGATCTCGGCTTGCGTCGTATCCGTGTCAAACACTCGAGAAAA +AGGTCCAAACGGCTTTGCCTTGAGTTCGACAGTGTTCTTGATCTTGTCGC +TTCTCGCGATGCTCGTGCACTTGTCGCTCCGCTCGGCTCCATTGAGtggt +ctggaaaattgaattttgaagtttccaaactgtttcaaagaattttcctG +ATCCTCACAGCCACTCGAATATGTGACGTCGCTTCAGAGACCTTCTTCCG +TGTAGTCATCGTTAAATTGGATGTCGTATCCTGAAAAATACGATAAATTG +AGTATTTGAGCAATAAATGGGTGTGCTGGTGCATTCAAAAAGTGTTGCTT +CGCGGCGCTCTCATCAGAGCGnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnTCTATAGT +TCAAAAGAACCGCAATTATTTACTCTTCATTttgtatggatgaatttttg +attcgtctgatataattttttttatgattaaaaaacaacgaaaaaatgtg +attttgtgcaatttcgtgaggttttttgattataaaaaaaagttttatca +gacaaatcaaaaattcatcaataCAAAATGAAGAGTAAATCATTGCGGTt +cttttgagctatagaactcctagaaatgtcaaaaactgaaagaggagata +catttttaCTGTAAATAACTTTcgaaaatgaccatttttgaaatgttttc +ttccggaaaaggaccatacaggattctataaccactaattagttttttaa +gaatcatttgaatcatcttcaaTCTCcgcaaaatcagataaaaaaatctg +aaattatggttttagacctgcaattgtaaTCGcgccaatatttttttctg +tagatcaaaatttaatttgcagttcggaaatgttctgtgggagaccgTGA +AATGaggaataataataatatatttacttgcaatgcatgggggaaataga +tagataatttggcaagaaatgggacctgtacaaataaaagaagtaaaatg +accagacggaccgactagagtcctgtgaaaaatgaaagaaaattcaaaaa +ctcccgctcaaaaattcgaaaaccatCTAGACCTTTCTGCGGGTTTCGCC +ACGAAAGTTCAATTTTaagcatgcgcctttaagcaGGATTACGGTATTTA +GAAGGTCTCGTCACGGAGAGCTTGCgcctttgaaaatatttcctTTTCGA +AGTTGGTCTGAATTTAAAATGAGTGTTCACccgttttcagcgatttttca +acgttttttcagctttttttctacttttttgattaaaaaattcaaaaagt +ttcagaatatcatGGTACTTGCCCTCGATATACCGCTAAGACCGCCGGAG +CGAGCCGTACTAGAGTTTTTATtgtaggattttttgaaaaaaaaacccgt +tttccgaagaaaattttttcagaggcGTAGTCTTCGGACCGCAAAGAAAT +CTGAGCACCTACACAAGCCGCAGAAGTTGTCAGCGACACGATGTGGCAGC +AGCCAGTCACATTATTCGCCTCTATCTTGATAGGGGTCGAAGAAAGAGCG +GTTTCACCGATGCTTGCCATCTCGTCTATGGCAACACGATTGTGTTGAGT +ACACAGGTCGCCAGACTTTTGCGTAAGCAGGATTTTTGCCGGAATTTTGA +CTTTTAAACGGGTTTTTCTTCCAGGTGATGCGATTCGAGCCAAAGAACTC +CTGTCCTATTCTTCCTATCTCgcagaggaggaggagagaagACGTAGAAC +TCGCGAACAGATGGAGAACGGGCTCATTGACAACTCAAAGAcaccgaaga +agaagaaaaggtcGAATGGAGCAGATGAGGACGAATTCGCTATGAAAAGT +CCAGTGGTCAGTACCaaaaaaaCTTGTCTGGactttttaaaatcgaaatt +ttcagagtgtcGCCTTGAAGAAGGACATCACAATGCGCGACGTCTTGGGA +ACGCCTCAAATCCAAAACATCGAGATTGACGATGATTTGGCACCGGCCAC +AGTCGATGATCTTGCTCTGCTCTATGGATTCCTTGGATCAGAAGCCACAC +AAGTTGATAAGTCAGTTTTTCTGccgaaaaattcgtttttgagcccaaaa +tcatcattttcagaacatttatCGATCAACAATCCTCATCAGCCGCGAAA +AACCGTGAGGAACTGATCCAAGACTTCGATTTCGAcgctccaccaccacc +gccacGACAATCATTCGCACCGCCCATCGACGACGATTTCGAGTTCCAGC +GTCTAAGCGACGAGATGATCCAGCAGTCGCATCAGACGCCAGTGAAAAAG +AGACGATCGGGAGAACGAACATTCGAGCCGGGACCTCATCTCGCCGAAGT +GCTTCTTTATGGACGATTGCCACTCGTCGATGAACGTAGGAGTATGGAGG +ATGAGATGGAAGACGCCAGGAATCACGGAATTGTAAGTAATTGGTCCTAA +AGTTGtcgaaaattaggtcaaatttCGAAGAGAAGCGGTCTAAAGATCAT +TTTTGACCCGAAACCAACATAATCTTTTCAGAACAACGACAACCTGGACG +TTCCTTCTGCCCTGGTCGATGTCCCACGACTGCCATCGCAAATCTCCCTG +GACGATATTCCATTTCCTTCGAGACCACCCCAGCGAACACCCTTCAGAAC +ACCGCAGAGCACACGGAAAGCCAAGTTCGATGTGTACAATGGAGAAGTGG +ACCCGACGCAGGCCGATAACAATCGGTTCAGAATTCCATTGGTAGGGTTT +TGACTGTCTGAAGACCctataaatttcgaatttccagcgAGAGATGAATC +GAATGATGGAGGACTTCTCTAGTCTCCACTACGAGGATGGCAAGATGCTC +AGAGTGAAGCCAGCAGCCAAGAGCGCAGTCAAAGAGCTGTTCAGATCTGT +TCCCTACTTCATAAAAGATCGtgagtagttttttttctggatttttgact +tgaaaatcgttcatttttgtctaaaatcgatatttttgacctgaaaatgg +tttttttcgacctaaaattggtcattttcgaactaaaaaaaatagttttt +gaccCTGATCATCTAGAATTTCTGCTTTCAGGACGCAACGCGGATACATG +GGACGTGTTGGATGTGGGTTATAAGAAGCCGAATTCAAGCATATCCGGCA +ACACTGTGTCTGAAGATGAAGACGAAATCGAATCGTCTAGTGGTTTTCGT +CGTCcaaaacaatacaaaaatttggagCCTATCGATTTGTCGAACCTGAA +GGTCTCCATGATGCCGTTGAAGGAGACGTCGCCAGTGTAAGCATTTTAGc +ctaaaaaaaccaatttttgactcaaaaatcaactgtccagcaaattgatt +tttagggtATCGGGAGAACAAAATTCAACTGTTTTCCCTCTTTCAGAATA +TCTCCACTCCGCCCAGTCGTCGATGGTATCGATATGGAGGATTTGGAACG +TCCAAGAGACCATAACGACGTCCCTCCAGAGTTCGATTTTCCAAGACCAG +AAGACGTTCATCGTGAGCCAGGAGAAGTTCCAGAGGAGATTGAATTCCCT +AGAAGAGAGGATAATGGATCCAATATCACTAAGATCTACGACGACGCCAT +GCTCGATGAAGACCCTTTCCCGActtccaaaactttcgaaCCACCATCAG +CTGGTGATAAGTCGGCTGCCACCATTCGCGAGGAGCTTTTGAGGTGAGTT +TTGGCTGAAATGCTTCATTTTCCACTgcaaaacgctgaaaattttagaca +gTGTGAGGAGGAGAGCCCGTACCCGATCCAGTTGGACAGCATGACTCCAA +TCGAAACAACATCTCGACGAGAAGCTGCGAGGACGTTCTATGTGGTTCTT +GGTtagtttaattttgaaaatctgagacttcttctgaaaattcttcttcT +AGAACTCATCAAAAACCGGCGCATCGAAGTCACTCAGGTGTCGCCATTTG +GACAAATCGACGTGCAGCTCTCGGCAGAAGACTTCGAAGATTTGGCGGTG +TTGGCAATGGAGGAGGAGATGGACGATGGCGATTTTTAATTGGACCCCAT +TAATTCtgtcatttttgtctgtataatgtgtttttacgacatttttcgtc +gatttttagtttgtcttttttctaaGCCAGAAAGTCTTGTTAAATTTAGT +CTACTGTAGAattttctagttagttttcattttctagtatttaaaaatta +tttttctttttaatttttttttgtcgggttctcaaaaaatcacaccCAGT +GCATGTATCATCCTAATCATgtttcatctcttttttttgttttaataaaa +ttctatttttgttgtttataaatttgcaaactttgttaaattCTTgagat +ttttcttcattccccGACTCTCTCCCCGACAATCGATTCTTCTGCCCGGC +GCGAAGGTAAACGCGCTCCACggctaattcaaaattttcgcatGCTAGCG +ATTGGCTCCATTGGTTTGCATGGAGTTTAATCCGGATAAGTTCATATAAT +TGCTCTTATTGCTTATCTTTATCGATCAttttttagggaaacttgttttt +gtctccttttttccgttcttttttgtgtttgcctttAAAAGtatcgaaaa +attagaaattttgttgtgaaaaattgtggaaaaaccACTAAATTATAAGA +ATTGCAGGtttttggtctaaaaattgctgaaaatctgaaaaattccgcat +tttttaacgattttccagtcttttttcgttgtttttttttcgagctgtaa +aattttaaaaataaaagaattttcgctaaaaaaaaGTGCTGAAACATGTC +GAAAATTGccttattttcagcctaaaaaacaataaaaattggaatttcgc +ctcaaataggctccgccccctttccACTCGATATTCTTTTCATCTTTCCC +GATTTGCCAGgttgtaatttcaaaaattttcagcactttccggcctgaaa +aatctctaaatttcctttttttttgcttaaaataggctccgcccactcgt +TTATTCGATTTCCCTGACTTTCCaagttttttcccaatttgcTCCAAAGT +CCCAGATCCATCTgacaaactgaaaatttcaagcgATGCCACCAAAGAGG +CGAGTCCGTGGTCCCCCGCTTCCAGCACTTCCAGAATCCCCAGATCGTCA +AGAAGACCCAATCGATGAGGTGGATCCAATGGAATCGCCAGATCGAGACG +ACGATCGAGATAATCAGAGACATCGAAATATGCCAGACTATATGGATGAC +GACTTTGATAACGATGAAGAGGAGACATCAGACGGCGAGGATGTCCAACT +TATTGAACAGGAGCATGATACGAATGTTTATGATGATCGAACCATTCAGG +GATTGGAAATTCGAATGAGATACACTAAAGTTACGCCAGATATGACTGGA +GATCAGAAGATGTTGGTTCAGACTGGCAGATTGGTTAAGTGAGTCAGGAA +ATTGGCCTTTTTCAAGCTCAAAAGCGCATTTATCTGCTCAAAAAGTACCT +AAAAATGATGCTTTTATTAGGAAATCATGGTTTCTTCGGTCAATTATTGC +TAAAACTTGTAATTTTCTACTGGAAATTGAAATGgctctgaaattcttta +ttttcagcttcgaaatcgttttatttttatttttttcctgccaaaaattc +attgaaactGCCTGTAAAATTGTctctttttcaacttcaaaatcacattt +tttcaacaaaaatagtgattttccAACAAACAATACTTTTTCTgtcagaa +atttctaaaaatttcaatttttgaccgaaaatttgctgaaaatggcttcA +AAAAGTCCTgttttttcgacaaaattgTCCATTTTTGACAAGAAAATCAT +GTTTCTGGGCATATTTCAGTCGTTTTCTAGTCgaaatttcctcaaaaatg +gcatttttttttgtcaatttcattaggaaattaaaaaatttcgggatttt +tagcTCCGAAAATCGCTATGTGAAGCcagaaaatcactgaaatttgaata +atttttttcaaaatttcagaaaaggagTCATCGATTCGGTTCGTCAGGCG +TTTCAGGCTCGAGACAATATCGGGGAAGAGCTGATTATCGCATCTCAAAA +GATGATTGTCGCTTTTAAAAGGGTAAGAATTCGAAAGCATTCGAGAAGTC +TGGcaaaaattccatgaaatttGGTCCACAATGACCGGAAACAGTCaatt +ttagcttatttttatcgattcttatagattttttcgatgaaaattgccaa +aaatcgagaaaattatcCCCAAAATGCACACCTTTCTCTCTTACAGGCCA +ACAACACGCGTCACAAGAAATGGAATCTGGTCAAGGAGTTCTTCATGGAG +CTCGACGCTCGTCTAGTGATGATGTTCGaggaggttactgtagccgaaaA +CCGTGCGAGAGTCTACAAAATGGTTGCGATGGTGGCGATTGAGCTGCTGG +TTCTGGGCTACAATCAAGAGTTCTTCCACTTTGTATTGGGATTGGTGGAG +AGTGTGAGTGACaagatttttgtgatttttgaagctatttttcatcaatt +tctagCCAAGAATTGAATCCAAATATGCCTGAAAATAAGCTATTTTTTGA +CATGTTTGTGTTTTGTTATTGACTAAAAATTCGTCAGAAATCGCAAAAGG +AAAATGCTTCGaaaattgaacgaaaattAGACTTTCCAATCGAATAACtg +attttttgtgtcattttttgttggattttgagccagttttgttatttttg +aacctatttttttgactaaaactTGATCAAAATTGGCTTTAAAATTCACC +GATTTCTAGTGgaaaatcgtcaactttggaTGCCTTAAAATTCACCCAGT +tagttaactttgagctcaattatctcgattcctttgagagatatcaaaat +tttgtcaactgataaaatgtttaccatgatatcagcaatattctatcagt +tgacaaatttttgacatctctcacatgaattgagataattgagctcaaag +ttgacgattaagtggggcttctattagattccacattctccatttttcag +tgGTCCGAAAGCGAGAGTGTCGCGTCACGAATCAACGCCTCGTGCTGCGT +CAGCTACATATTCGAGACTGGAAAAACGCACAATCGCCAACTGACGGGCG +AGAACTTCTCGGGATTCCCACTCGAAGGAGCCTATCGTCTGTTTGCGGTC +CTGAAGAGGGCGTTGTTGGATAAGGAGGCGAGCGCCAGAATCCCAGCGAT +CAAAGGAATGGGAGTGATCCAGAATTGTGCCATTCCATCGGCATGGCCAG +TTGAGGGACGGGAGTCCAGTGCCAGGgagtgtgagttttttttgtggatt +ttgaaccatttttcatgatttttggacttttcatagattttagaccattt +tttcatgcattttgggtcattttccattatctttggtctatttttcatgg +attttgaaccatttttgggcatttttatttcaaacttttcagtgCTGACC +CGCTCTTGCCGTGACATGTCTTGGGAGTGCCGCCTGGTCGCTATACAATC +CTTCATGCCACGTGACGAAGACCTTCAGCTTGTCTCCGACATCGCCTACT +ACGACAAATCGACAATCGTCCGAGTAGCTGCACTCGAGCAGTTGGGCAAA +ATGAGACCACATCGGGATTGTAGGGAGAAGGTCGTGCTCGTCGACATGTG +TTTCAAGGATCATGAACGTAAGATatttagagaaagagagatacCGTAAT +CCCCTTCTAGTGATCTAGATGGCCCTGGTGACAGTCCTGATGGCCTCTAA +CGACCCTTCCAACAGCTAGATAGCCCTAGACAGTCCTAGTGATCACCTTG +ACGGCCCTAGATGGCCTTAGACGACTAAGCCGTTCCTACTGTCCCCTAGA +CGACCCTAGACTGCCCTAGATGGATCTAGTATGGATCTAGTCACACCTGA +CGGCCCTCGAGACCCCTAACGGCTTTTTTAACAGTCCTAGTAACATCTAA +CGTCCCTAATGACAGCCTAGATGGCCCTAGATGGACCTAGTGACACCTAA +AGGCCCTTCTAACGACCCTAAAGTACTCTAGTGACCTCCAACTGCCCTGG +TGACTCCTTAGACGACTTCAGATGACCCTAGTCATCATTCACGATCATTC +TAACAGCCTTATGGACCCTAATAGCCTAGACAACCCTACTGACTGCCTTA +GAAGGCCCTAGACGATCCTAATGACCCTTATATGCTCTAGTGACGACCCT +AAATGTCTCTAGTCATCTCTAATGTCTTTGCTGACGGCTTTGACAGCTCT +AGACGCCCCTAGATGGCCCTAGACGCTCTGAGACGGCCGGAGACGGTCCC +AGTGACCCCAAAAAACAACATTCCCATTTCCAGCGGCCGTTCGAGATGCC +GCAAAGATGGTGCTCCGTGAGTGGGTGGCTCGTCTTGCCCGCCGATACGT +CAACAAGGCCAAACAACAAGATGTGGTCCCGATGCGCGGTCCAGACGATG +AGGAAGCCATCCCACCGCCAACAGGAAAAGGATATATTCTTGCTGGACAG +GGACTCTGCCTTCTATGGCTTGTTCATATGGTGGATAGTATGGAGAGTCA +CCTAAATCTTCGCAGAATGATGACCCATTTGTTGGATGTTATTCGTCATA +TGTACCTGTGTCATGCGGAGCCAATTAGCACGTTTGCTGAGCAAATCGTT +GTGGATCTGAAGGAGACCCAACCGAATTGTCCGGTTCCGTTGGTGACGAA +ATCGACGATTGATACGTTGTTGGTTGATAATCCGTTGAACGCTgataagt +gagtttttaaaaatccttttttagcCAAACTGAACTGCTTTTTTCAGCCA +AGACACCAACACGACCCGCGCGATGGTGATGTTCTGGCGCTGTCTCGTCG +AGTACATGTCCGATCGAGCCAGAAACGAAGGAGACAAATTCCACGCGATG +AGTCGTTTCACCCACCCGTTGGGTACCATGTGCGAGAGTTTGGAGACGTT +TTTGAATCGAGTCAAAGAGGAGGAGGTCCCACCGTCTGGCGGAGGATATC +ATGAAGGATTTGAAGACGACGTCTATGTAGTGCAAATGTCGATTATGGAG +AATTACCTCCCGGTGTTGAAGTACTGTCAACAGGATCAGTCTGGTCTCGA +CGCCTACAAGCAGTTGCTCATCTCAATGTTGATGAATCCGTTTTATCAGA +AGAAGGTGATGGATATCATCGTCCAGGAGCTGGGGCAATTCTATAAAGAC +GATCCGCATGAGTTGTTTTCACTGATTTGCGCGCGGACCAGTGAGATGAG +AGACAAATACGATGGTTATCATTTTCCGGTGCTCGAGGGAACGGTTTTGA +TTGGAGAGCAGAAGTTTAGGAGGGATTGGAGAAATGAGATTGCCGCCGGG +GGGACGccgaagaagaaggagaaggatgTGAGTGTGGAGGGagattctgg +aagattctagaTGGTTCTGGAAGGCCCTGGAAGGCAGAAGACTCCAGAAG +CTTTTGAAAGGTTCTGGAAGGTGtttagaagattctggaagactcgggaa +catttcgaatgattctggaagattctagaagataCTAGAACGCTCTAGTA +GTAGCTTGTGGAAGACGCTGGAAGGTTTTTGGAGATTCCCGAAGTTTCTG +GATAATTCTAGAAGCTGTCGGAAGACTCTGAAATACTCTGAAAGATTCTA +GACGATTCTGAAACATTCTAGTTGGTTTttggaacattctagaacGATCT +GGAAGGCTCTAGAAGATTCGagagaattctagaatcccttggaagtttct +ggaagttttttgaaggttATAGAAGTTGTCGGAGATTTCTGGAATATAAT +GGATCATTCTGGAACATTATAACAGGCTCTAGAAGCTTTTGGAAGATTCT +GGAGCACTATGAAAGATTCTAGACGATTCTGGAGCATTTTAGAAGTCTCT +AAATGCTTCTGAAAGGTCGCGGAAGATTCTAGAAGGCTCCAGAAGCTGTt +ggaagtttagaaatttcatatttgCAGCTCGTCAACCGTCACATCGATCA +ATACGAGATAAAAGTGCTCAATTGCTGTCTGAAGTTGGCACTGCTGAAAG +AATGGATTCCAGAATATGATGATCGGTATCGGGAGAAGGTTTGTAGCTGa +aattcgactgaaaattatcaaaatgaccatttttcatgccttttttttca +gctccgcGCCCAAACCAAAGCCAAAGACGACTCCACCAAAATCTGCGCAA +TCGAGTGTCTCGGAATCATTGGCTGCTACGATTTCGACCTTGTCGCCGAC +GATTTCCGTGAAATGGCTGACTTCCACTTCCAAAAACTGGCTCGCCACGA +TCCGGTGACCCCAGAAGAGCACATGGTTCAAGCATCGGTGGTCCTCGCAC +TGGCCGATATGTTCGTTGAGAATCCCGATAAATACACGGATAAACTGTAC +GAGCCGCCGTTGGAGCACTGGAAGAACGCGGAGAACACACCGACGTTCTT +CGCTGATATCATCTGTTCGGATCAACATAAATCCGGATCGGAAATTTTGG +TTCGAACTGTTGAAGCACTGTGTCGAACacttttgaattcgaaaatcgat +cCGACTTGTCCCGCTTGGCAGAGATGTATTGTTACGTTGATGTACAGAGC +TTCGTTCAAAATTACGGATCACTATAGTGCTAGACTTCGATCCACGATCC +TCGTTACACTCCAATTCTTCTGCTCCATGaatcagtgagtttttgagcta +ttttcaactgatttctAGTGgaaaatggtggcctaactttgagttttcta +ggccaccatgactTAGAAATGTCCTGATATTCACCTGatgcgttttctag +gctattttactatgatggcctagaaaaaacaacttgcaaaagttaggcca +ccgtgtTAAACGACCTAAAAATAGCATGATATTCgcctgatgtgttttct +agactatttatcatggtggcctaacttttgcaagttgagttttctaggca +gCCATTCTCAAAAATGGCCTGATATTCCCTtggtatgttttctaggtcat +ttaccatagcggcctagaaaactcaatttttgaaagttagtccactgtta +aaatggcctagaaatggcttGACTTTCATTTTATGTGCTTTCTGAGTCAT +TTTAACAAGGTGGCCTAACGTATGCAAGttgagtttcctaggccatcata +gaaaatgacctagaaaacaccaGGTGCATTTTAGACTATTTCTATACCAT +TTCCCATGGTGTCCTAGAAAActaaacttgcaaaagttaggccaccatgt +cctTAAAATCCtataattcgaaatttctgatttcagaCGCAACCAACTCG +TCGTCGTCCGATCGTTCCGTCGATTCTTCTCCCTCTGGACCAACACCGCC +GACGTTGGtcttctcactgaaaatcgcaACGAGCTATTCCCGAAGCTGAA +GCGATGTGCTCACGCGTTTGCAGCTCTGACACGTCATACGGTGCTTCCGG +CTGACATGCAGAAAAATGTATGTGGAAAAGTGGGCAGAGTCAAAGGGGCG +GAGCTGAAATGcaagaatttaaatttttgaaaaagtggacGGAgcctttg +aaaaatatgaaaatctctaaaagtCCTTTAGAGATCAATGGATTTTTGTA +CTTCGAAATTTGTAGGATTTCGAATTCCTgagttttcggaaaattgggcg +gagccaaaagactaaaagggggcggagtttgatgataaaaatcgatattt +gcAGTTCCAACCGTCGCACATCGAGCTATTCGACGACATTTTGGACGAAA +TCCATGGACGCAGTGCGACGAATCTCGTCGATTTCTATCTCGCCGCCCTG +CCACACATTGAATTCGAGAGCTTCAGTCGACAGGTGCTCACCAAATATCA +TACGGATCTTCAGTGCTCAATGGAGGTGAGTTTTCAAGAATCAGGAAATT +cgaacgttgagctcaattatcttgattcctgtgaaagatatcaaaaattt +gtcaactgataaaatgttgctgagaATATTagagacattttatcagttga +ccaatttttgatatcttttacaggaaatgagataaatgggctccaAATTA +CCGGGCTTTTGCTTAACTTGATCAAGTCaaattctctaatttttgaccaa +aaattaCGCAaacaggattactgtatcctcGATTCTCGGACATAAAAACC +AACAGACTTTTCCAACTTTGCAGCTCAACGGCGAGGACATGGAACGTTCG +CATCGTAACGAAATTCGTCGTGTTCAGCGAAAAATCGCCAAGCTCCTCGG +CCTAAATATGGACGATGGTGATATCGAGGAGATGCCATCTACAGTATCAG +AACTCCGCCCAACACGACGTACGGCCAAAGCGACAGCAACGTTGGATGGG +ATTCAGGAGGAGGACAACGAGGATTCAGATGACGATAATCAACCGGGACC +ATCAACTGTCAAACCAAAACGCACACGGGCGGCGCCGACGCCAAGAAAAG +CGCCAGCGTCTGCACAGAAGAAGAGCAGAAAAGATGCGGAAGAGCTAATG +GCCAGTCCACCGGTGAAAGCAGGCAAAAGTGAGTggaaaggggcggggct +tagctggacattttcgaaattgtggCTCTAAAACAGTTCTTGACACtaga +aaaggggcggggcttgattgggaaaagaggagaagcgtaaataagaaaaa +agttgcGGAGCTtacattttttacattttttaaagcatAGGGAAAAGGGa +taagggggcggagcttaactagaaaaaagaaaaaaatggcgGGACTAGGC +CGAAAAATTGGTATATTTAGTAAGAAAACGAGGCGGAGTTTAGATAGGAC +AAAGGGGTTGAATCTATCCATTGAAGGGGGCGGAGATTACCtagaataaa +acatttttcagtacacattgtagtttgtagtcctTGTAGCCTAGCTTTTA +TAATTTGAAgccaattaaaattttgttttttccagaaccatCTCGTCCAA +TGACGGCGACTCGTCCATCATCACGTACTGCATCAGCCACACCGATGCGT +ACAATGCCGCCAAGAAGTGCGCGAAGACTtaattaattgattttttcaac +tttttttaaacccCATTTATTCGTCCCAAAATCTCAAGTTTCCCCcagtt +ttctttaaaaatctcgaatttctaCCTAATTTTTCGTCTTAAAATCTCCC +CAAAAGTCCCCCCTCCTCTTCCAGTCGACACCCCACAGTACTGTAATTTC +TGCGATCTCTCCTTTTGTTTTCCATGCATAATATCTGTATTCTATTTATT +TTTACCAGTTTAtatttcagtacaaaaaaggCCTGgaagaatctcaaatt +taaatttcccgcccattttttaccaaaaaatctCTCTCCACGTCGGATTT +TCCCACCTGaataccaaaaattcaaatttcccgctcgtttttttttgtca +ttttagtttcaaaaaaatgcaaaaatctcCTCTTCCTTCTCTTATCACCa +ttccccttcttcttctcattatCACCGATTCGACAAACGCATtcaatgta +atttttttttgttgggtcccaccacgaaaactacagtaatcctggatCTT +TTGTGATTTGATCCAATTTTCTTCTGTGCAATCGTTTATTGATTTATTTC +CAATGATAATGATGAACTATTAATTTTggattcgaatttttgaaaaaaat +caaaaatttccaaatttgaaaattcaaaaaaaaagtttcagcaacatttt +tttcaaaaaattccagattacGGTGGCGAAGCCAGATGGTGGGACCTACT +ATCGTTTCTGGTTTGTTTATGGGtgtttttcgattggaactacagtaatc +ctcattgTGTTCACTTCGATTTCAATGTGCCGAAGATACAAATTGGTGGC +CAGTCAGGACGAAGAGgtgaaaagggggcggagctttggaaaaaaagggc +GGGGCCTCACTTTTTGAATCTGAATTAGaacaaaaaaggggcggagccta +attttctgaaaatttcagatttccgaaattcaatgATGTGGAGAAtttta +agaagaagaagacgtgaatACTTTCGAAGTGatctatttgattttttttc +gtattttctgaatgaatatggaatctgaaagtttagatttttttgatttt +ttttgaatttttcgaatttttcaaaattttgggatttttttcgaattttt +gggatttttgtgtttttgaatttttgaattttttgagttttttgaagttt +ttgggatttcagatttttttggattgtttttggttttttgaatttcggaa +ttttgggatttttgaatttttcaaattttcagaattaattcCGCGACCCA +ATGAACTACTTTCTATGTGACCTTCCGACTTGTCACGTCTATTTTCTGAC +TGTTGAGTCCTATTCAGCTAATTGGCACCGTTACAtttttatgcagtttt +tttttcaattttcatattttttctttgaaagaaaaattttaaaaattcca +aaaaactgagtatttttGGATGTTCAGCCCAaaagttgacttttttcatc +ttttttcatcCGTCAAAATTCTCCAGCGACTTCCCCGCGCGCCTTCTCCT +TTCCTCCCCTTTCTTATACGGCTTCCGCGCCCTTCTCTCTAGTGTGAGCA +CTAGCTCAATGGCTAACTCTTTTGCCTGTCGATCTAGAGTTCGCGGGTTC +GAACCTTCTCGGGAAATTtgtctttttatttttgtaatttttccaggaac +aACCGACATGGCTCGTACAAAGCAAACCGCGCGTAAGTCGACCGGAGGAA +AGGCTCCAAGAGCGCAGCTGGCGAGCAAGGCTGCTCGCAAAGCAGCTTCA +GCTGGAGGAGGAgtgaagagaaaagagaaaaaacatttccatAACCTACA +AATTTGGAATCGGCTCAtcgtgagcttcaaaatgagtataatcatgactc +tggacttcaaaaatttcaaatttcccgccataacttgtccacgaggagtc +CAAAACTAAAAACGTTCAGTAGAGCGCGCTTACGTTGTactcaggtaaac +gattctgaattagatctgacttcattcggaattagatcgaataactcgaa +attctgaattagatctgagttcattcggaattagatatGGACTAGATCTA +ATACCGAAGTTgccacgagaaatgcgccatCAATGACTCAGCTGCCGCGG +ATGaatcgttttgtttttttgttgtcctaaatttttttcgtcaggAAAAT +GGGTATTTCTCTCaacttttgccttttttttcgctcaattatttaaacta +tttttctggaacatattttaatgtgttgtgcacgtttttgcaaaatttta +ggtgaatttttttaggaacagctgaatattcaaagttcaatttataTATA +CGACTTCTATAGAAGACAGTAATTCTATGAATCGACAAAAATACgacgat +tttgaagattttaaattcGGAGAAAACTCTGCAGGTAAGataatttttgc +ctttttcagcTTGAAGGATTACGTAAAAACGATGCAAGGGATCaccgaaa +aaaacaagaaaaaagagatgataaATTGCTCTGATAGTGAGCTCAATTTA +CACAAGTCGAGAAGGCCTTACTTTCGGAAGCCGTGTCTTGTCATGAGCAG +GTTAGTTTTCGAAAGTCTGGTGGACAAAGAAACATGCGTGAAATTGCAGG +CTCTCAACCGAATGTGTCATGACCCGATTAaaacgattcaaaaatttggg +atttgttGTATAAAACAACTGCTCTGATATGAATTTATTTGGATTTGCAA +AGATTTGAGTACGGAAATTATATTGAAATGGCTCAAGTAAGTTTATTATC +AACATCACAAAGccaaaatcttcttttttcagttaaatcaACATTCATTT +CATAAAGAATATCCATCTTATCTACAACCGAAAACTATGacaagagaatt +ttcaaaatcgaaaatatggaCGAGCGGATGAATTCGAATtgagatgtttt +tttcataaatttcgtcactttttttttcttatctcaaTGTTCCCATTATT +CTCGCtgatctcatcgttttcttttttgctgatccCATTCATTCATTTGT +ATCACACCCCTCATTTTCGTTCCGATTTCCTATAACTACAttttaatcta +tgtttttctttttctcatacttgttctgttttcttttttaataaatttta +ttataaataaagtgaatggcgttgaaaagaaaacaaaaattgaaaagtgc +gcgctacgatgctccgaaatcccgctggtctgttcggaattagatctaat +tcgttcgtagttcattcggtgttcgttcggaattagataagctaaattct +gtattagatcatgccacttctatttacgaacgaacccagatctaattccg +aataaAGTCAGATCTAGttcagaatcgtttacctgagtAACTAAACCcag +aaaataggtttttttttcagtttccggTGTTTTCGACTCTTCGAATCTTT +GGGGAAATCGACGGGAATCGAAAACAAACAAATCGGGGAAATTTTCTGAC +ACTTTCCAAACATTGAGCCAAAAGAgccgaaaatttttcttgtcCCAACa +atatctaaattttctaatttttccaaaaaatgggaattcgaagcattttc +tggaaagttttgGCTGGGAGAGGTAACATCTCtttttgaggattactgta +gaatttctaaaaatgttcaaaaacatatttttagctCCGGAAAATGGCGG +CTGGGTGGATAGTATGCAAGTGGAACACTTTGATCCATATACACCGGGAC +AGCTCACCAAAAACTTCACGGCTACTGTAGGTTCTCATATTTGCACATAG +CTCACAGCTTGctcatttcttgaaattttcgtcATAAAACTTATTAAATC +TTGCTCAGCTTGCTGAGAGCTTCgaaataagcccaaacacgactagtcta +gcgCTATTTGGAGTTTTGACCtacgcgttgcggtcgcgtcgcggtttgTT +AGATTTAAACTCAAAGCTAAGcgaatctagtcgtgtttaggctcatttga +aagctctcgGCTAGCTGAGCAATATAATGAAGgtttgattttgaaagttt +gagaaatAAGCGAGTCATGAgtaatttgagattttcagaaaaccttaaat +tgctcaaaagttgctcttttttgtactcctcgtggacaatcaaaaatttt +ggagcttATCCATGACTATGTTTATTTTAAGGCTATTAAatatgaaaata +gaaaacgcgctccattCCAGGTAGCCGATGAGATTAGTGTGACACGTGGC +ACGACAGTAAAAGCGCTCTACCGAGACGATCAATGGATTTATGTGCAAGT +TTCGGATGGAAGGAAAGGATTCGTTCCACAGACATACTGTAAATTGTTGC +TGAATgcgcgaaattcgaagaaaGAAGTTGTGGACAAGGTGAGGGCGCTC +TATTAgacattttgagttttgtactcctcgtggacaagctgtggcgggaa +atttgaaactttttggagttgggtcatgattatactcattttgaagctca +cgaTGAGccgattctaaatttttggttttggaaacgtttttttcaaattt +cagaagaaagttGGAACTGCTGGAACAACATTGGATCGAAAATGGGAGAA +GTCGAACTTGCAGCGTTTCATCGACAGTTTGCCAGTACAAAAAGAAGAGG +GGGAGGTTTTCAAAATggtgggaaatttgaatttcgaaaaaagcgcGCTC +TTTTAgacattttgagttttggactcctcgtggacaagtcGTTGGCGGCA +AATTTGAAAGTATTCGTAGATAGGCCATGGTGATacttgttttgaagctc +ttgagaAGCTGAATTCGAATATTGcaaccaaattcaaaattttttgttcc +aggACGAAATCTGTGAAGCTCAAATTCTGTCGAGCTTCGATGCGTCCGCT +CCAGATGACATCACCGTCAAAGAAGGGGAAATTGTcacaattctgaattt +ctcagatCCCGAATGGATTtatattcgaaattctgagaaccAATCGGGAT +TTGTGCCGGtggcaaatttgaaaattccagatgagCATcgcgaaattcag +aatcgtgTGCCAAAGGAGAAGTGGTGAggaattattgatttttcagcagt +tctgaaagttctggaagCTGTGGAATcgccaaaaattcgaaatttcaaat +gattttttcagtggaaaccccaaaaaattcaaatttctcgctgaaacttg +tccacgaggagtccaaaatccaaaatctctaatagagcgcactttctttA +TTCGCAAcgtcagatattcagaattagCTCtctgagagcttcaaaatgag +tataatcatgacccaactttcaaaaatttcaaatttcccgccaacgactt +gtccacgaggagtacaaaaCTAGAATTTGTCCGAATTGgttgtttttgca +tttaaAATGCGCTCcgctgaacaaaaattttgtggctcgaatttttcaaa +tttcccggggcttcagaacttcaagaattttaaatttcctacCTTTTCAG +GGAAAACGAAAATCTCCTCGTGGTCGAACCATTCGCCGGTCGATCACCTC +TCGACCTGACCGTCCGTCCGGGTGAATGGATTCGTTGCACCGGCAAGCCA +GTCGACGATTGGCTATGGGCGGTCCGGATAGCCGATGAGAAGCAGGGATT +CATACCGAACAAAGTCGTCATTCTAGCCACCGATCTTTAaccttttttcg +ttgttttttctccttctgaTCAAAAGGGGCGTggtctaaaaatgaaattt +tcgatttcgatTACACCATTGTTGCTTTATTATTTCAGTATTATATAGGC +CCGGCTTAGATCTGAGAATGATGGAGAGACAGTAATTGATTGGGGGGAAG +GGGAAAATAAATTactaccaaaaaaaagaaattaattgGGGGATGGGAAT +AGATTCTGACGGTAGAGAATAGATCATTTGAAGTGAAAGAACCAgatttg +acagatttttcaaaaaatttgattttttttgagaattaaaaaaaaaggac +agTAGGATGAGAGAGATACTGTGGAGATACAACACAAAATTGAACTGGGA +ATTTTATTTTAGAGAGATAAGGGGATATGGAGAGGGTGTCAGAGAGTGAT +GCCAATATTACAGATTTTAGAGATTTAGGGATTTAGAGTGTCGGCCGTTC +CAAGACCATTCCACATGTGCTCTTCAGAAGTTCATCGCGTAGCCGCCACA +GTGCTTTGGTGACGTCTTCTTCGCGGGCAACTGGACGACCGGCTTcagtt +ctctgaaaattgcaaaatttgagttttgaactcctcgtggacaagtcatt +ggcgcgaaatttgaaatttttcagagtagggtcatgattatactcatttt +gaagctctcagaGAGCTAGCTTTGAATATCTGGTCAGTAAACACACTCTA +CtgacaattttccagattgttGAGTATAAACGCGCTCTATCGACATTAGT +CAAGATTTGAACGAAAGAAACTGTAAAATACACAGAAAACACCCATCGCA +AAATGTTATTGAATGGGAAAAATGCGAAAAGAGGCTCCTTACCCTAATCC +AATTGGTCGGTGGTCTCGCATTGGGATTTGGTTGCGTGTTTCGGATGGTT +GATCCCAGATTCTTCTCCCAGCGAGACACggatttttggcgattttgaGC +CAGCGATTCAATGTATCTGGAAAACAATTGATaattaaggatgagcaatt +gaTTGCCAAAATTCACTCAAAACTTCAGTATTTTTTAGCATGAACAATCC +CGCCTAAAAGgtcaaagtttggaaaaaaaaacttcgttTTCAAATAGAGA +ATAGATATTCTGGAGCGAAATTGGCTTGAAATCCAATtcaccgtaaaact +tgtaatagaagggcccccacattgagctcatttatctcggctcccttaaa +agatatcaaaaatgtgtcaactgataaaatgtttgtgatatcctgataaa +caatttatcagttgacaacttcttgatatctttcaaaggaggcgagataa +attgactcaaagtcaaaagttagagggcccttctattacaggtttttttt +ctggccaAACTCACTTCAAATACGCTTCCGAGTGCAGCACTCTCTTGGTG +TGGATCTGATTGGGCGGCGCGATGAACGCGGGCACCACACATCGGACCAC +GGTCCTTCCGACGTCGGCGATTTGTGGGACttgttgcatttgctgctgct +ggggttgttgtccctgttgcatttgcatcatttgctgttgttggggtggt +agtggtggtggtccttgatggtattgttggtgttgtgggtgctgctgctg +tggatgctgtggatggtggtgttgctggGAGGATGATGGCCCCTGTTGGT +ACATTCCGTTCTGTTGGGCTGAATGGCCAGGctgtaaaaaatcaataaat +cgataTTGGAGGATTCTAGGAATATAAGATCCAAGGCTGTAGGGAACAGG +GGCTTACAGCCTTGATAAGAACCCAATTCCTCCAGTAGGACCTACCTGAT +AatgctgctgctgctgatgGTGTGAATGATCTACATGCTGTTGCTGATGC +AACCCTCCACCATTCATCAACTGTGCCTGAAGATGTTGTCCAACGGTTCC +ATTCTGATGGTGTCCATTGACGTGGTGTACCTGCTGTGGTGGCGCCTGCA +TCGTCTGTGGCGGTCCCGTCGGTGCGTTTCCATACGGTTGATGACTGACA +CGTGTCGGCTCGCCCGGAGCACTCATTACTCGATAGAAGTTCTTGCCGAG +CTGCGTTTGATGAATCGTCTTGGCCGACGTTGGCATGTGCTTCTCCTTGA +TGTGACGATGAAGACGTGGCAGTGAGGGGAACGGTTTTCCGTCTTTTCGA +TTCCGAAGACACGTCATCCACATGCACACGAACTGTTGGTCGCTGTCCAC +TGAAAGAAGAGGAGGGTTTTATTAAAATGTCAAGGAAATGAGCAATTACG +CTCCAATGAtagaaggaggagaaggaagATAAAAATACCACATACATCtc +taattcttcaaaaatttcaaattttgcgcCACAACTTGTCCATGAGGAGT +TCAAAACTCGTTATTGAGAAAATACGAGTCgtgtactcctcgtggacaag +cTAAAGcggtaaatttgaaaacttttgaagattGAAGCTTGCTAAGAGCC +taattttaattgaaaatccaCAAACATCTctaattcttcaaaatgagtat +aacaAGCTTTGgactcctcgtggacaagttgtggcgggaaatttggaatt +tttgaacgaGTTAGGTCACAActatactcatttcgaagctcttcaaattt +ttcaaatttatccgCCATaacttgtccacgaggagttCAAAACTCGTTAT +CGAGAATTGGgctcctcgtggacaagttaaaacgggaaatttgaaatttt +tgaagtccaaagtcatgattatactcattttaaagctctctcttcaaaag +aaaaaaaaactactcaCTGATAATCTGACTAGTATGGTGTTGAATCACAT +GCTCCAGAAGCGCCGTCTCCGTATCGTATTGAGTGTCACAGGCGGCCCAT +TTACACGCATAGATCCGCACTTGTCCGGGAAGTAGTGTCATCGCCTGATG +GGCTTTAATGGCATCCTGTTTCGCCTTCTCGACGGCCACCACTTCCGCAC +GCAGCTCGTAGTGCTTCTTTTGCTCTTCCGACAgttttttccactgaaaa +tatGGCAAATTTAGAAGTTGCTCTCTCTCTACAAGATGCTCCTCCCTAGA +GAGCCTCTTACCTCTACACCAACTATTCTCGACACGTCTCCAAACCCAGA +ATCCGGATTCTCGTGCATAATTCGCTTCCTGACTTCTGCGGAGAATAGAA +TGTAGCCACTTTTGCTTTTGACCGCTTTCGGTGTCACTGGCGTTGATGCG +GTTTGATTGGCGACAGCGGCTACTGTGGCTGCCACGTCTCCTCCAGATTC +CGACGGCGTCTCAGGCGGCGATGAAGATGTCGCCGCTGTGACCGGCGCCG +GGGTCTCCTCCTTGACGTGACGTGGAGGATGGCTACTGCTCGTAACCGAC +TCACTGCCATCCGTGTCGTCGTCCATCATTTCATCGAGATGATCCAGTGG +CATGACGCCGTCGCCGTTCACACGTGGTGAGAGttccttttccattttta +ttggCTGCTTGTAGAACAGAATCTCTTCATTCGGGATCGACACGTGCAGT +TTGTAGGTCTGTAAAAATTCCAAGGATGAGGGGGGAGGGATTCTGGAGAg +ggcggaaattcaaaaatcaaaatttcggaagaCGTGGGAAAGCTCTCCTA +GAAGACGTCAGGCGATTCTAGAAACCAATCAAACCAAAGcttctggattt +tcaggtgagtggtcagatgacgtcatctggattCAATGGATTCAGGAAAG +CGAGAGCCATGAAAAAGAGTGGGaatcggattttcagattttgagtgTCG +CAGGCTACGGTCAGCTGACGTCATCTTAAAGTGCTGGATTCAGGAAAACG +AGAGTCCACGATTCTATAGGGACTTCTAGATCCCATCACTGTTATTCTAT +TCTACTTGTAGCCTACATCGGGGCTCCATGGCAACGCTAATCCCCCGGGG +GCCCCTGATTCTCATAGCCCTCCGCTCCTACTAGAATGCCCTATGCTTCT +AGAATCTAGGATCAAAGGGGGCGCCCTACAGTACCACCACCTCCTCTATG +AAGATAGACGACGGCGGCGGAgacagagaaagagaaactCCGAGTTGGAG +CGGCTAGGGCGGCGGTGGCGGCCAAGCGGAGGTAAGGAGAAGAAGGGAGA +GCTGGCTGCAGGCAGCAGCAGCAAGCCTGCAGCCGGCatcagaagagaag +aagaagattctaCTGCTGCTGCCTGTACGCACACACACAGGCTCTTGTCG +TCCGCGCCAGGCAAGCAGGCAGGCCGATAGACCAAGATGCAAGTGAGGGG +GGTCTCCGCTATAGACTGGGCAGGCACGTCAGCATAGCGcacacagcaca +cacacacacacaccacCATCTGcctccccccccccttcttcttttatttc +aCGACCTCCTTACTGTCTACCCCACTCTCCTCGTTCGGTGTGCTCTCTCC +CTTGGCAAGCCACTCCGCTCTCCTAATCCGTCCCACTCTCTCGTCGAGTG +TCTGTTCGTCTGTTTCCTCTTGGGGCCAATCGATGCGCGCGCAGGGACGC +ACAGAGAGAGGAGGAGGCCAGAGCGAGGGTAGTGGCCATGTAGAAGAAAC +GCAGAGTGACGTTTCTGTCTCTCCTCGGGGGGTTCTCGAATTGAAGGGTG +GCGAGGGGAGGAGGGTAGGCTGACTGTGTGAGAAGACAATTAGTGTTGGC +TGCTGCTGCTGGTGGTCCACTAGGAGGAAACTAGGAGAAGGCagctgctt +cttcttctgcgGCGTCGGCGCCTTCTGAATCTCAGCTCAGctcaaaaaga +aggaaattccTAATCTTCTGCTGATAATGACGCTGACGACTACAAAGACG +TGCTCAATGAGCAATGCTGGGTGGAGCTTAAGAAAACAGGGGATGAAGCC +TAAAAGGGATGAAAACGgatagaaaaaaggagaaaatgagTGATTATATA +TGGCAGAGTTCTCTTTTATCAACGGGACGAAAAACTGACAGCTGAAACCT +CCGAAACCTCCGAGGCGCGAAAAAATAGATCACAAAtcgatctacagtaa +tcctaacgATTTGTTGGAAGGCTTACTGTAGGTCTTGATCTGGAGAGATT +CTAAAGTTTAGTttgggggtactgtagttgagACATAGGGGGTAACctac +aaaaatccaaaatgctCAGgacgggttactgtagttctgtATCTGTTTAT +CTAGATGTATTGATCTACAAATTTGATCAATGAACGAACCTTCAtctttt +tcatggattttgcaTAGTCCAGATTCATCGTTTGCACATCTGTAAACTCG +TTCGCCGGATCCGGATAGCCAATCAATGAGCAATCGTCTGGAGCATCGGC +AGTGCCGTTGACCATTGTTTCGCACACGAAGACGTCGCATTCCGATATTT +CGGTTTgacgttctgaaaaaaaagagattttcgaGGAACCAAGACTTACT +GTAGGTTTTTATCTGGAGAGATTTTAAAGTTTAGTTTGGGGGTATTGTAG +CTGGAGACCTAGCTGATAAGGAGGGAGTAATcgacagtaatccaaaatgc +TCAGGAGGgttattactgtagtttatgTATCTGTTTATTCAGATGTCCGA +AACACAGATAAAAGTATTCTGatgaaagattactgtagctacagCCTGTG +AACGCAGTTACCGTAATCTACAGTAGCCTCGTCGACTGACCTCATTTTGG +GCGTTTttgaggtacagtaatccggaaaaTGTGTGTACAGTGAACcccaa +aaaatcaggattttgTTCTCCGCCCCTTTTAGATAAAGATTACGGAAGCA +CTCGCCAAAAATCCGGATTTCAAGCCCCTCCCTTTTTTCGGTAACATGGG +GGCGTTTCCAGGAGTACTGTAACTGCTACAATTCtaaagattacggtagc +tacaGTACCTGGAAAACCCGGAATTTCAAGCCCCTCAAAAACTCACGCTT +CGTATAGAATTTCGCTGGCATCACATCGCAAGTTCTCTGTATTTCGCACA +ACTTGCGCGTCTCATCATTCCGATAAACACCAATGACCTCATTCTTAAAG +AACAGTCGACCCTCGTCATGAATCGTTTCCGATGGACGAGCAAACCAGGA +TCCGGAGAACCATTCCGATCCATCCGCCTCCTCTCTCCACAGCTTATTGA +TCCGCATCACATCACAGAGGGGTTTCAGGGGATTGAACACCAGAACGCAT +TGTCCGAGCCAAAAGAATTTGCCAGTTGAAGAGCGGATCTGTTGGTAGTA +GATCTTTCCGTCCTCCTTGGTCGACTCATACTCGAATCGTTCCATATCCA +AAGAGACTTCTAGACGTGCACGATCCTCCTCATCATCGTCTTCCACCTCC +ACAATTTCCTtctcttctgaagacgtcggaTCTACCACCGTTAGAATCCT +CTTTGGCGTCACTGGCTTTCCCCGTTTCGTGCATTCCAACTCCTCATCTT +CTGAACTGTACGGCCAGGAtctcaatttcgaaaagtaCTTTGGTTTTCCA +TGATACTTGTATTCACACAGATAGACGTCTTCTTCAGCGAAATCGCTCAG +AATCTTGGTAGAATACGTGGCAAGCGACACAACTGCACACTGTCCACGCA +GTCGTTCGGCAAGAATCGTGCCTCGGAACGGAGTCAGAAAGACTTCTTGT +TTGATGAATTTGCGGCTAGCCAGATGAAGTGTCTCGTCGGGACGATAGAC +CCAGAATCCTTGAAGAGCCTTCTCGCCAGTTTCGTCTTTGAACGTACGCT +CGATTCGAAATATGTGGAGGGGAGTCTTCTTCTCGTCGGCACGCGCGATG +TAGGCGTAGCACGGCGCCACATACTTGACACCGTCGACTTCGACGTCCTC +CATTTCCACTTCGGATTCCTGGAAAATGAGAGGGGGATAGATCATAAAAA +GGCGTAGGTGTGTCCAGAAGGCACTGGGGAAATTCGAAAGGATCCCAAAG +AACTCTAGAGGCTGCTAGAAGCTTTCGAAGGATCTTAGAGATCTTTAGAA +GCTTCCGAACGACTTTGGATCCTTCAAAAGGATCCGAGAAGCGTCATAAG +gattctagaatcttccaAAGGTTCCCAAAGGCCTCTAGAGGATCCTAAAG +AGCTCTTGACGGTTCTAGAAGCTTCCGAAGAATCctagaagtttgaaaac +gAGCCTAGAGAGTTCTAGACAGTTCTAGAAGCTACCGAAGGATCCTATAT +AGCTTTAGAGGATTCGAGAGGATCCAAGATGCTTCAGAACGATCCTAGAG +AGCTCTAGACAGTTCTAGAAGCTTCAGAAGGATTCTAGACTGATCTAGCA +GATTCTAGAAGCTAAGCTTTGGAGGGTTCTAGAAGCTTCTTTAAcacaaa +aactcacatttctcTTAATAACCGCTGCTCTTCCACCCATCGCCGGGCTC +TCTCCACCCTCATCCGACTCCTCCTTCGCCTTGACCACCTTCTCCTTCTC +AATCGCCTCATCGATATCCTTCTCGATGACACTGTACGCTTGCGAGTGAA +TCACGTCCTTGCACTTCGCATCTCTCTCCACAATGAACGCCTTCTGCAAC +TGACACGCCGCTTCATAGATCGGTGATTCGAGCTTCGCCAACTCTCTTGC +TGTTTCGAACAAGTCGAAAAAGTCCTTTTGAAGTTTGTCGAGCCGTCTAT +ACCGACACTTATCGATATTGATTTTAATTTGGTCCATTGTGAATGGCCAT +TCAGCTGGTGGCACTCCAGCAGCCTTCATTAGGTCCGGAAACTCAATGAA +ATAGTCTGCCCAACACTTTCCATCCTCATCCTTCTTACTGTATAAGGCGG +CGAAGATCGACGTGAAGATCGTACGAAGCTCGACTTGTACCCTCGGAGCA +TCCTCTCCTGAATCCAACGATCGTTTCATTTCGAGAAGATACTTCTGAAG +AGACACAGCCTCCTTATAGATCACAGAATCAGTTTCATTGAATTTGCAGG +CGTTGGAGAGCATGAGCATGAAGTCAGAGACCACATCAAGAAGGGTTACA +TACTGACGATTCTCCAATTTCGCCTTGATTCTCATAAAATCCATTGGCTT +CTTAATCACATCATAGTAGCCTGGAAACTCTTCTTTCGTCGGAAGACGCA +TGAAATTCACAGCCAGCGGGCGACTCGAATCGTCGTCGCTTCTCACGTCT +TTCATCGATTTGAACAGTCTCCACATCTTCTGTTCTTCGATGGGCAGCTG +GAGAATGGCTTGGTCAATTTGACGTTGCTGTTGAATCATTTGTTGACGAG +CCAGCTCTTCTTCATTGTCCTCTGGACCTCCATACTTCTTCTTGCGGCCA +CGTGTCTccgtttttggggttttccTGTaaaaacccatagaaaaaagtcc +aaaaatcatgaaaaatggtcctaaatccagaaaaaaaaaagtagtttaaa +atccattgaaaatggtcaaaaatctaTGAAGAATGGTCTaaaatccatgg +aaactagtccaaaaatcatggaaaaaaggtcctaaattaatgaaaaatag +tcctaaatccattaaaaatggtctaaaatccatagaaaaagtccaaaaat +cataaaaaatagctcaacatccattgaaaagagactaaaaatcatggaaa +atggtctaaaatccATGTAAATGGGTCGAAATCCATggaaaatgatctaa +aatccatgaaaaaaaaacagaaatttcggaccatttttcatgaattttgg +ataatttttaatggattttggATCAAATCTATGGAAAGTGTGTCCCAAAA +CTTACATATTCGTCAAATTCGACGCTGATCCATGTGGTGTTGCTGGCATG +GACCCGGCTGGCATCATATACGGCTGTGGTGTTGGTTGCCCATATGGTAC +CATCATGGGGTACTGCTGTTGACTCCTCATTCCATCATACGCACGAAGAA +CCGCCTTTTCCAATTGGATCGCATCCTGATGAATATTGGAACCGGGCTCG +TTGAACTGTCTCGCGTTGGCGAACATCCTACGACAATCCGCAATCATCGC +GTCGACCATCGGATACTGATGAGTGTCGATTCGGGTTCGGATGATTTTCA +TATCAATTGGGTTCTGGATGACTTGATAGTACTCGGGATACACCTTTGCC +GATGGGAGGTCTATGAAAGCGCCCGCAGGCCAGTAGGCCAAGTTTCCAGG +AGCTCTAAACTGATGAATAGCATTCCACAACCCCTGCATCATCGTCTTTT +GTTTCATATAGGCAGCGTTCGGGTCCACAGGAGGCAtggatttccgattt +ttatagCCCGGCGTTGGCGTCCCGTTCTCCCTGTTCTTCTTCGGCGATTT +TCGTTTATGCGACGGTGGAGGCGTCCGACTATCATCTGAATCCGTATCCG +GCATCTCGATCTTCACCTGTCGGGCGCGCGCTTTCGGCTTCTGTGGGGTG +TTGGGTGCCGATGGTGCCGCTGGCTCAAACTGGCTCACATCGAACGAGGG +AACCAATTCCTTACACGTGGCAATCGTGAGATTCCGAAGCTTCTGAGCCG +CAATACAGACATCCGACGACTCGAGATTGTATTCGAACGCGTTGGAGTAC +ATTGTCATGAGGTCGGCGATGAGGGTCTTGAAGTCGTACTGCCCGTTTTT +GAGACGTTTGTTGATCATGAACAAGGAGACAGGTTGCTTTATCTCGTCGT +AGTAGTCAGGATAGGATCTGGAAGATTTTTTGGTACAGTCTGAGTCATTT +TGAGGGTATTTAGGACCCCTTGAAGGCCCTTAAAATAACTTTGAAAGCCT +TAAGCATTCCTTTGAGGTCGCTAaaactgatattttgataaaaattgata +ttttgataattcgGTATCACTGTGGTCTAATTTACggccgaaattttgag +agtgggcggagcttaggtacGGTAGCGAaggatactgtatttttttattt +ttcataattttgaaggtatttttctttgattttacgatgaatttggaacc +tatttttcacaaaaattcttACAGTAACACCAAAATGACgagctggaatt +ttgaaaaaaaaaataccctaaaacctgtaatagaagggcgcccACATTgt +catcaaatttgagcttatttatctcggctgctttaaaagatatcaaaaat +gtgttaactgataaaatgtttgtgatattatgataaacaatttataagtt +gacaacttcttgatatctttgacaagaaccgagataaattgggtcaaagt +tagaggcctattctatcacaggttttaagACTTTTTAgtgatataccgta +aaacctgtaatagaagggcctcctaacttttaacttcaagccaatatatc +tcggtttctgtcaaagatattgaaaagttgtcaactgataaattgtttat +caagatatcagaaatattttatcatttgcttcttttttgatatctctctt +aagaatcgagataattgagctcaaacttgacagtggggggcccttctaat +acaggttataAGCCCCAAAACTCACTCCTTGCAAGGCAACTCCAAAAAGT +TATCCGCCAACGGCACATCCTTATCCATCGCATTCCGAATCGTCCAGTAC +ACCTTCCACATCGGTTCGTCAGCCTGTTCCGTCTCCTCATCCTCTTCAGA +ATCCTCCGAAAAGTTGTCATTCACTGCGACAGCGGTCAACAGAGCGTCAA +CAAGTCGTGTAGCTTTGGCCCTTCTCATCGGATGAACTCCCTTCTCTTCC +AGCTTCGCAATTTTCTCTCTTACTACTGTCTTCAATTGCTCAGCATCTTT +CCAGATGTCACTCCCCTTTCCACTGAATTGTTGAGCGTTTTTGAACAGGA +GAAACAGGTCGTCCTTCAAGTGCTGCATTGTTTCATACTTCTTGTCCTTG +CCGTTCTGAGCAATCGTTTTCAAATCGATCGGCTTTGCAATCTTCTGGTA +GTACTCTGGAAAATCCTCTTTCGAGTGTAAAACTCTAAACGGAGGACAGA +GAAGTCGTCCAGAGCTGTCTGCGGCTTCTAGAACAGCTCCTAAAAGATCA +CACAACATGTAGTCGTCCAGCTCCATTGGTGAAACATCACGTGACGATGA +TTCTCCCGTCTCCTGCGCGACTTCTGAATCCTCTTCTTCTGGCGTTACGT +CTTCCacatcgtcgtcgtcgtcgtcttcctcttcctcctgCTTATCATTC +AAATACTCTCCGGAATCGACCTTCTCACATGCCGCATTGTAGAGCTCCTG +GATCTTCAGCATATCCTTGTGCTCATCagaatctttctgaaaatcgattt +ttggctattttcagctatttttcgcCATGAATTTACCTGATAATAGGCCA +GATTATTACTTATAAACGTGTCGAAATCGCTTTGAAACTGATCAAAAGTC +TGATAATCCGGATTTTTCAGCTTGTGTTGAATCGTAGTAATATCGATTGG +CTCCTTGACAGCTTCATAATATTCTGGCTCTAGACGACGTGACGGTACTC +GGAGAAAACTCTCGAATATCGGCTCATTGGTGCCGGCTGTGCTGCGTTGA +CGGCGGATTTTCGACATGACATAGTTGCCTTTGACGAGctgaaattgaca +aaaatgagtcaactttattaattttggggcgttttttcccgaattttcga +ccaaaaagGCCAGAAATaacctaatttttaaattttccccACCTCAATTT +CCCGTTTCTCCCTCTCGGCAAGAGTCATTCGTCCTTTCCGCTTCTTGGCG +GCGTTCGATGTGGACGGCGTATCCTTCTCGGGCTCCAGCTCGGCTGCACG +CTTTCGTTTTgtggtcatttttaggcctgAAATGAGGGGAAATTTAGAAG +tattcagatttgaaaaaaaaaaagaggtttcaagaagaaaaatggaccga +aattcatgaaaattggttcaaaattcatgaaaaatggtcagaaaataatg +taaataggccaaaaaacatggaaaaccggaccaaaagccatgaaaaatag +cccaaaactcatgaaaaatCGTCCAAGttacatgaaaaatggccaaaatc +tatgaaaaacgatccaaaacaactaaaaaactattttttttaaagcaaat +aATAggcaaaaattggattttcttcCCAAAACGGGTTgattttcaagcca +tttcgtttttcaaacatgctgaaaaaaaagaggtctCGAGAAGAAAAGTG +GACCGAAATCCAtggaaaatggctcaaaattcatgaaaaatagtcagaaa +tccatgaaaaatagcccaaaattcatgaaaaacggtccaaattatatgaa +aaaataggcaaaaattggattttctggCCAAAAACGGGTTGATTTCAAAG +CCATTTCGTGATAAaagatgttgaaaaaaaaacaatatttttggcctttt +tggaccaaaaacccgtttacagagataaaaaatacaaaaaattcaatttt +tcgggcaaaaaaacctaatttaaaggcatttttcaaaatagaaaccCCGT +CAAAATAGGTATTTAGctggatttcgaaaatctatgAGAACCCCATTCAA +AATTACTAAAATCAAActtattttctatgaaaatccCCTAAAATGGCact +tttcactaattttctccccttttctccttctcaaagtcctcaattttcag +cattttcagctctaaaacGTTCAATTATATatttctttgtatttttcctt +gaaaaatccCTCAATTTCCCATATCCTAATCTCATTTCCCCATCGGTAAT +CCGTGTCTAAACCCTGAAAGGCGGCGCGACGTGCGCgcgaaactcgaaaa +tttgaaaattggagaggAGGAGGCGGGGCGATTATTGGAGTTGGAGACga +ccgaaatttcgaataaaatgAGTTCCAGGGGGTAAAAAATGATGGGGAAT +CgatggaaaatgagaaaatcgagataatgtGTGATTTTAAACcgaaaaat +cggggaaaattgatgaaaaattgacgaaaatcgGTTCCAGACGAATTTTC +GCGCATTTTTACGATAGAACAGAACCCAAAAATAGGGGCGGGAAAAGCAA +CGAGTGTGTCCCAACACCCAGGCCTTCAAAATAACGAAAACGCGCGCGAA +TTGTGTTGGCTGGGTGCCAGACACAGCGTTGTATTGGTTGGTTGAGGAAA +GAGAGAGAAGGGCGAGTGAGCGCGCAGAATCAAGAGACGCAGCGCGAAAC +GGGTCGGGGCCGATGAGTGAGAGAGAGCGTGCACGCGAAACGCGCCAACG +CCGCCGCCGCTGTTTTCGACTCGTTGTGTACGCTTCTTCGCTGGTGTATT +GATCCAAACAGGTTAGTACTAGGTTAACaacatgctgaaaattgttttta +agcCATGAAAGCGATTAAAATGCTGCTGAAAACACCAAGAAAGTGTTATA +ATTGGCAAGAGTGTTCAGCGAAGggaaattcaatatttttctttgaaaat +atgatttaaaaagtttaaaaccAAGAGAAACTAATAGAAAATGTGTGTAA +ATCATGTTTTTAGCCCGAGAATCCAAAAAGAATCAGCGGAAAAcgctcga +aattcaaattttaaatttgcgCGCCAAGCGAAAAGCTTGACGCGTTTCTC +GTGCAGTGACTCTCTGCGCGACCTCGAATGGGTAGAGAAATGGAGTGACT +CTCCGACTGTGCGCGCGCAACAAGGGCAGATGGTACACAGAGAAAATACA +ACACAATGACACATTATATAAAAGAGAGGAGAaatctttcagaaaaccaT +GAGTGAACGAGGAGGACAGCCACCACCGAAAAAGCGGCGGACCAACGACC +GGCAACGATCGAAAAGTGCAGATTTGACGGTGAATAATGAGTATGAGGAT +GTGGTTGAAAAACTAAAGGGAGCAGACAAAGAATCGGCTGTGAAAGCGGC +GAAAAAGCTGAAGCAGATGCTGTCGAACGCCGCGAAAATTGGCGGATTCG +TGGCGCATCGCCGGAATCTGGAAGATTTAGTTTCAGTGTTTTCAAGGGAA +ACTGCATTGCTAGGCACTTCGATGTGAGTGTgggaagctgaaaataatga +aaattcgCTAAACCTCAGGTACCACGAAGACATCCATAGGTACTCTATAA +GTATCCTTGCAAATTGCTGTTATATCGATAAAACGACGTCAACTGGGAAT +CAAATTCGACGAGCTTCTCGAAGTTTCCTAGATCAAGCCGGTTAGCGAgc +acttttttatttgaattctaGTGTTTCCCGCCCGAAAACGATTGTGCATT +GGAGCGTAATTGCTCTCGAGGTTTCGAGGAGcggagaccccgcaaattcc +ggggaaataaaaaactggagaaaagaatcggggaaaagtgggcggagcct +aaaatgcaaccctggcacggttttgccgcagggtttttctgcacatttgg +acACGGTCATGAGGGTGCGGAGCATNAATTGCatccctggcacggttttt +NTNgactccgcccactttccccggagtttttttttcccggaatttgcggg +gtctcgaGGAGCGagagcttttttaatgtttgaagtcgttaagagctttt +ttaatgtttgaagtcgttaaaaattgaaaaaaataaagtcgggaaataaa +aaaataataatgtttgcgcgtgggattgcgtgctttaggtgcgaacaccg +cgacggcaaaatacacattccctgaaattttccccgaaatttttgctgtc +tgcccTCCTTTAAAGCAtaatgttcctttaaaagtgCTACCGTAGTCTTT +agtgggaaatttgaatttttcagtccGAATCTTCGAAAGCACCACTTCCA +ACATAGAAATCCGCGTCGCGACGTGTCGATTAATCGGAAATTTGTGCAAT +AATAAGGAGCTGGGACCAGTTGGCTGTCAAGCAACACGATCCTTTTCGAT +CGAATCGCTCTTCTTCTAGAGTCCACAAACGAGAATATCGTCACACAATG +TCTTCGGATTTTTCTCTTCCTATCGAATCATTCGTTTACCCGGGTGAGTA +ATTCTagttggagcgcatttgcattatTTACATTTTTATTATTAAACCCA +AAAAGGAATGTTTAAATACAGAGAGATTACTATAGTGGTACACAGTTTAC +AATAAGCTAGacagaggaaaaaagaaattatatgttattcttgtgcaaaa +aaattggagttgtggccgaattttcacacaagttaggccaccgtatttca +aggagaattttcgaaaacacagcctccaatttttttgcacaagaataata +caggaaaaattttcaaaaaaaaaactttttttgggggTCCGACATCATGg +gagttttagaattctgagatttcagCAGTTTAATGGGTCTGTTTGCGTGG +CTGGAATTGGTGCTGTCCGGACTTGTCGGCACGGAACACGTGGTTTGGTT +GAATGGCCGGTTGCGGCTTCTCGTGGACCCGTTTGACAGCTTCAGTTGGA +TACGAGCGGTCCATCTGGAAAAAGTTAGATTTGCAGGTTTTGGTAGTTTA +GTTGCTAGAGGACTCTGATCGTATGGTTGTGGTTGTCTAGGCTTACTAAG +GAGTCTATTACTGTTTCTCTTGCGTCCAAGCTAGCGGCTAGAAATGCTCT +GGAAGGTTTAAAGAAGCCCCAGCAGCACTGAGAGCAGGTTCCAGCCCCTG +CTGGGACGTTTCAAAAAGCTCTGAAAGGATCCTAGGCTTATCCTAGAAAA +CCTCAGAAGGACAGATGTCTTCTGGAGGCTTGGTAAGTTTCTAGACGATT +CTAAAagcttctagaaggttctggcCACTTCTAGAAGGATCCTGATGGAC +CTAGAACCCCCAGATCGGTTCCTAGAGTTCTCGAAAGATCGGGAACCTTT +TGAAATCCTTCTAGAAAGTTCGAGACGGTCTAGACGACCTTAGAAAGAca +gacgtcttctggaggcTTGGAGGCGTATCTGACGGCTTCTAAATAATTCT +GACCGCTGCTTGACGGTCCTAGAAGTCTCAGGACCCTCTGGATGCTCCTG +GAGCTTTCAGATCGATTCCTATAGTCCTTAAAAAAGTCAGAAACCTTCTA +GAAGGTCCCTAGCATACCCCAGGCTATGGCCCATATCTCACCTTTGCCGG +CAAATCCGCATCCAAAATCTCGCGAACGACTTCATCGGAGCTCTCCGAGT +TGGTGTGCTCATTGGAATCCGACGCCTTGCGATCCTTGCGATTCACGATG +CGACGTCCGCCAACCATGGTTGCTGGTGGATGTCCGACCTTCATCTCAGT +CGTCTCGTTGTTATCCATAGCGCTcattttcggaactttctgGAAGATTC +GATAAAGGCTTTGAATATAAAATCAAtgtggagaaaaaaaacgagtggTG +ACCTCCTCCGTCCGAGGTAGGCAGAGCGAATGGCGCTGAGGGAAGGGACA +TAAACAGAGTGCGCACTGAGAGACGCAGGGTAGGGGCGGAGTCACATGAC +AGCGGGGCGCGGGGCTCCCTCTTTCTCACAAAAACACATTCAacgaaaac +aagaagaagagagtaTGTGTGGTTAGAAGACGACGCCGATCTATGGCTCA +CTTAAATAGAAAGGaagaaaagggggcggagcttgtttACTGCCGCCGAA +CATACACAACACATTGCGAAATAGAATGTGGAAGTGatcggtttttgaaa +ttgagagaatGGTCAGTTGAATGAGATTGGCAGAAGATGGATTGGTTATA +TGTTGATAATGATAGCGGAGGAGTGTGACTAACGTGATAGTTGCTagcca +tcaactttgagtcaattcatttcggttactgtaacagatatcgaaaagct +gtcaactgataaaacattgatcGTATTACGAtgaacatttcatcagttta +tcactttttaatatctttcacaggaaccgagataaattggctcaaaaata +gctcTTCTGGTTTGGACCCCTCATTCGACTTCACATTCAAGATAATGTga +ttttgagagacgcagagaaaaatgtaaaaaaaaacagtacaAAAATAGCT +GTTTTCGTTTCCAAAATACATTAAATTACACATGTTTATGATGGGCATGA +CATGtatttttgtatgtttttgaATGGGAAAGGTGTCActttaaaggggg +gggggggggaagtgACGCTGTAACACTTGTATAAAACCACCGAGATGGAC +AGAGTACTCGGTGTGTCAGGAGTACTGTAGTCTGCTTGTCAATGTACAGT +ACTTCTCGGCAAgctttcggttttttttaaatagattTTTGGCTAGCTAG +TACTGTATATGTCGAATTAAACAGCAAAAGGTAGACTAGAAGTACTGTAC +TTTGGGAAACAGGAAtcgattttcgatattttgatCTTTCTAAAATTATC +ACCAGCTGACACCTTTGGTCTTTGAAAGTCCTTCTTTCTTATCATTTGTT +CTCTGATCAGACCCTTCAAGTTGTTTCAGCCAACCAACCTAATCTAGGCC +AACAAACGAATCCACGTCATGCAGCTTACTTGCCGAAATGGTCGTTTCGT +GTGATCGCTTGTTTACAGGCACGACGATCACtaatttctctgcgtctcta +gaatgttctagatagggagagagagagagaagagggggaaaagaaaaatg +gcaaatatttaaaaaaaactgatttccaGGTGATTATGCTGTCGAATGGA +GGCTTCTATTTGGGCAAATTGCTGGCTAAAGAGGAGCGAAGAGATGAGGT +tgtgaagattttgaaagtgCTCCTCAAACGGCATCGAAATGATTTGGATA +GACAGTTGGCGAGAAGGTAGGAGAAGAGgagacatctggacacacagaca +gacagagATGTCATTTTATTCAGTGAATGCAGCGAACACGTGATTGGAAT +GTTCTTTGAAAGGAACAACAACAAGCATCGACGGCAATTTGTGATTGATT +TGTTCTCGAATTCGATTTGTATTAGAGAACAGTTAGTTGGGCGAAAAAAT +ACGGGGGGAGAAAATGGGGTTTTGGGACACtgttttgaatgattttggat +catttttcatggattctggacgttttttttttgacaatttggggattttt +ggagcatttcctttggattttgagccatttttgacgATCTTGGGACAAGT +TTTCAAGGATTTCGGCCATTATTCAggtttttttggcattttccaATGGA +TCTTCAGCCAattttacatgatttttagatcagttttgatcgattttaga +catttgttgatgattttgagacaatttttcaaggtttttttggacaattt +ttaaaggatcattttccattaattttgactcatttttcatgatttctagg +acaaattttcGTTATTTTGGGGCCATctttcctaaatttttagagcacga +tttcaaagattttagatcatttttcataattgttggaccatttttcacaa +aattagGGATACtttttcatcgatttgaacaatttttcatgaattttaat +gatttttccaaggatttttggccatttttcataaattttgaatcattttt +tcctaaatttttggcatttttcatgaatttgagatctttttttcatgaat +ttcgacccatttttcGAGGACGTTTGGTCAatttcactgattttaggact +atattttttcatggatttcgactaaattttcattattttttagacaatta +tccatggttttttggaaaagtccatgaaaatttaaaaatcgaaaatctat +AATTATAAACGAACATGtaaaataagtttttgaagttttatagttgtagg +attttcgatttttgaattttcattaaattttttgcctatttttttgcttc +ttttggttcattttcgcaaaatttaaTCTTAAATCCATGAAAATTACCCA +AAATCCTTAACAATTGGTTCGaaaatctatggaaaatgcttcaaaaacta +tgaaaaatgagccaaaaaaaattggaacatggttcaaaaaatcatgaaaa +atgggtcgaaatttatgaaaaattgttttaaaattttttaaaatcctaaG +TTCATGAGaattggggaaaaaaatccataaaaattttacctgaaaatcat +tctgaaaaaagactaaacaccgcaaatggaaaaccaaaaattaaggaaaa +tggtccaaaaccccatgaaaatcgaaaaatctgcTTACTAGATTTGGGTT +TCTAagtcacaaaaatttgaatttcaaaaagcgatagtttcaagttcaaa +ttcgtttcaaaaaatcaaaagatcagGGAAACCCCCCTCGTGTTTGTTGT +TTACGAGTCTCTTTTAAAAGTCCACACATCCCCAGACAGACGACAataaa +agagacgcagagaaacagacAACCCCAaccccattttttcagaatggagA +CCGAAAAGTTCATCGAACAACTCCTCGCTTGCTGGCTTCCCGAAAAACAT +CGAATGCTCGCCGCGTTCTCCCAAACAGCGTGGGGTCGTGCGAAACTTCG +AACTTCTGGAGCACTCGACGTCGTCGTTGACGTCTTCTCAACTTCAGATT +CTATTGAGGAGAAGCTCGCCTCCGTTGCAGCATTCCGACATTTCGTGCAC +GATAACGCCGGAATGCGTCATTTGagtgaaaacttgatttttgtgaaTAC +CGTAGTCCGAGATGTGAACGCCTACGTGGAAAAGAATCGTGCCGAGTGTG +AGCCTACGGTAGACCTGGAGTTTGTGCAGAATTTGAGAGCAAGGggcgag +ggggcggagccaggAGGGGAGAGACAGGATGTGGAAGAGCCGGCGGAGAA +TAGGTTGCATAAGGATTTCTATTCCATGTGGAGCTACGATACACCGCAGA +CGTCACCGAAGACGTCGCCAAGGAGAGCTTCAATGTCGCCACAGTACAAT +GCACCGTCGCCCAGCTATAGTTTCCCATCGTCGGTGGCGTCGAGTGCACC +GTCTTCGCCGGAACCCAGGAGGTATACTACGAcacctaccgtaacctaga +aatatttttattttccatatttgtactttttttgaaatccaaagaGCGAT +AAAAATTGACGGAAATCCGGATCTTTTAAATATTCTGTGTACTTTGTCGT +CAATTTCGACGCATTAATGCTAGACACCATATTTTACACCATATTtcacg +acaaaatgcacagaagTTCAGACAAtgccaactaccgtaacctataTTTG +TATTTCCcgttttttggacatttttacTCGAAAAAAGCGATAAAAATAGA +cggaaatccaaatttcgcgctcaaaaaaaccgaaatttcgaatttctgtg +cattttgtcgtaagcTTTGATGCTGCATCGAATCTGACGACAAAGTACac +agatatttgaattttcgctgGTTTTTCATCGAGTTTCCTGTTAAAAGCCa +gctaaaattcaaatttctgtgtACATTGTCGTCAAGTTCGATGCATCAAT +GCTAAACACCGAAtcttacgacaaaatgcacagaaattaaaaatttcggt +aTCCAGAGCGCGAAATTTGGATTCGTGCCTATTTTTATCGCtttttttCC +gattaaaaatgttcaaaaaacaacgGGAAATACAAAtataggttacggta +gttgtcgttgtgagaccaaagctccgattttttgtactagTATAATAGAA +ACTGGTGTTTCAGACCCAGTGAAGGAATTCTAGACGATTTGAGTGATGTC +GAATCGGATAATggagaggagaaggtggagaaggagaacgaagacgagaa +gaagagacggcaggagaagagTGTAAGTGTGGACTACGGTAGATGGCTta +gatttggatttctaggccaccatttgctcgaaaaatgcattgTCGCATTG +CTGACattgttttctcgtttttcgtcattttgagcatgatggcctaactt +ttgcggGTTGGGTTCCCTAGGCCACCACcccaaaatggcctagaattgaT +CTCATATTCACCTAGTgtgtttcctaggccattttgaggtggtggcctag +aaaactcagtttgcaaaagttcggccatcaCGTCAAAATAGTCTAGGAAT +CACACTAAATGAATatcaggccatttctaggtcattttgaagtggtggcc +tagaaaacccaacttgcaaaaaaattaggccTCCATGGTGGACTTCTCGG +TCATCATGAAACTTGCAGATAATCGAAGGAGAGCTCTGGCTGCTGACATG +GCTCTCCCAAGACGATCACAACCTGCAGTTCCTAATCCGGGCCGACGTGG +TCGATGCCGTCGTCGCCTACCTCCGATCCACTGCCGACCCGGACTTCCGA +ACGTATCGAGTGCTCCGTCGAATGGCCACCCATCGAACCTACGTCTATCG +TCTTCTGGACCTTCAATTTCACGTGCGCATACTCACTGGTCTATGCGCCT +CGCCGTGTCGAATGCTGAAATACGCGAAGACATGCAAACACTGTGATAAG +TGTTCAGAGCATGGACGGGAGATTCTGAGAGAGTTCGCGAGCCACGTGGA +TAACAGCTATGGAGACGCCCACATCAATTCGCAGTTCACAAAAGAAGACT +TTGTGCATCGGACGAAGGCGGCGATTGCGAAAATCGTGTTGGTCAAGGAG +AGGATTCGTCTGGCGAAGGTGCCGGCGCTCACCGAGTTGTTCACCGCGTT +GGCACATGTGATGAGCTCGGTGGAGAACTTCGAAGAGTTGGGAAAGATGA +CGACGTATGAGAATGGACCATCGTTTGTGTCGCAGATCATTGGAGCGCTG +TCGATTTTGATTAGTGGACAGAAGATCAAGTgtgttttggagaaaaaatg +aatttctgtgcattttgtcgtaagaTTCGATGCCTAGCGTTAATGCATCG +AAATCGGCGACAAAGTACACagatattcgaattttcgctgGTTTTTCATC +GAGTTTTCTGTTAAAAGCCagctaaaattcaaatatctctGTACTTTGTC +GTCAAGTTCGATCCATCAACGCTAAACACCGAAtcttacgacaaaatgca +cagaagTTCAGACAACGACAACTannnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnGGCCTAGAATCCAAATCTcgtgta +gtcctctcggagaagagcatttttgaacaatttaaACGAGTTAACAGTGA +TAAAGAACAGATAAACAGGTGGttgtaccgtaaaacctgtattagaaggg +ccctctgtgatAAATGACCTATattaaatcgaatttttttttacagagAA +CTCTGCGAAAACGACATGTGGTATTTTCCGGTGATCGACGGCGGTGAATG +TGtacttcagaagacgtcttcagTTGAAGAACTTTTACACTTTACGGATG +AGAAAAACGAGGAAATCGCGGCGGCACCAATGCGAGCCATTTGTGAGAAC +AGTCACTATTTCGAAGGAATGTTCTCGTCGAATTTCGTCGAAAAAACCGA +GgcgattcgaaaattccagttgCAATCCGAGTCGTGTCCGCCTGGGGATT +TCCGACTGTTCATCCATCTCCTTGCCACGTGTACCGGGCCATGTACGGTA +GTCGCGTCGGCCGAGCAATGTGCGAATCTGTTGGCGGTGAGGGTTTCGCC +TTGGAAAATATggatgatttttgaattttttgcagcTCTCGGATCAATTC +CTCTGTCCTACGATATCCAAACAGCTGTGCGCGGATGATGGACCACTACG +AACGTTGctaaatgggcggagcttgcaCACATTGCTACCAGTGGCTCTAG +CAACGAATGCACATCCAACGTAAgttttaggtcatggccttGATAGGTCA +tcatattgaattttcagccttctCGACACCGTGTACCTGACTCTGGTCCG +CTTCTCAtcatcagaagacgtgacgaaGGCGCTAGAAGCGATTTGTCAGA +ATTCTACAGTAGTCAACACGTTTGTCACAAGTTTAAGAACGTTTTTGACC +ACTAAATGTTGATTGTTTGTTGTGCTAATATCGGGTATCTCGATTTTCTT +GTCCTAAAaataaacgatttttttcaaaagaattttagATCAATGTCTTC +TTTTAGGcgaattttatcgatttttgaatagttCTCATCGTATAACCAAT +GAAATTCATCGCAAAGTCGACATAAATAGACCAGTTCtgatttagaaatt +ctgaaaaaatgccttcaaattttttattcggGTCACGACTGGAGgagaat +taattttttgtttttttcaatttttatattttttgcaatatAAAACTTGT +TTATCTGTTCTTTATCACTGTTTATCACTgttaaaattgttcaaaaatgc +tcttctccgagaggactacacgAGGTTTnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn +nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnaGTCCTCTCGGATAAGGCt +agagaaaatatgaaaatcaagcgggattttcatattttttgcgaatttcg +ctgattttcaggcttttcagaatgtcaaaaCTCCTTGAAGAACGTCTAGA +TGCTTGTGCGAGGTTCGACGACGATAAATATTACACAGAGTTTCAAAGCT +ATTACAATATTGTCGCTCAAGTGCACTCAGTGGTTTTGACCGCCAGAAAT +GTCTATAAaataaacgatttttttcttcaacagattttttttggcaacaa +aaaatcaaatttcaaatcaattgTCCTTCTTTCCCTCATCTGATCCTTTT +TTCGGCGATTCTGGTGCCACGTCATCACCATCACTGTCATCCATTTCGGC +GTGCCGTTTGTCCATATGATCGATTTCGTTTTTAACGTCTTCAAcgtcct +gaaaattttcgaaaaattgaaaattgcaagtttgtagtttgtagtctctc +cTCACCTTAATTCGATGATCATTCGCAATATCATCATCGTCGGGTGCAAT +TTTGATCGCTCCTCCAGATACACAGAACGCTCCCATGACCAATAGAAGAC +cggtcatctgaaaataaagctagtaaaaagaataaaaaaggaaaatcgcC +TAGATGGAATCGAACTTGCGAGCTGTCGGATTTAAAACAGACGCGTTGCC +GGCTGCGCCACGGCGGAACACAGAATTGATGGGCGTCTAGGGCGTATAGA +AAAGGTGAAGGTGGTGGCGCCGAGAGCCAaagttgggggggggggggggg +aggtgGATGAGTCGAAACGAAATGAAGAATTTCGATTTCGATagttttag +gaaattttagaTCCTTTTGGGCCTCTCAAAAGTCACAGTTTCAGactcaa +tggagcgcacttacCTCCACCACCGAAATCACTGAAAGCCCCAACCATAA +GCCAGCTTGTCCTCCCAAATCGTTGATCACATTGCTCACCTGTAGAAATT +CCGAGATCTTCTCAATAGAGCACACTTACCGTATATCCAGCAGTCTCTGT +ATACAACTCATAACTCAGCGTCTCCAAGAAAACTTGTAAGATCATTCCGT +TATTATTATACCATTTTTGACACGCTGCCTTATTggcaaaattggaattt +gatgAGTAACAACTGCCAACCTGAAGACATCGGGGACATCGGGACACTAA +gatttacagtaacctactCCGGcggatgatgacgtggcaacaTAGTAGCT +GGTTGATGGGAACTGAGCAAGGGATACGGTAGGTGTGTAGGTGGACTCGT +CACATGGCGGATTACAAGAGCATTCGACTAGAAGATCGATGTTCGGGTCG +GAATTGGTTTGGTTTCCTTTGAGACCTTGGAGGCAGtccactgaaatttt +ttttggattttctaccTTTCGTAGTTCTCATAGAACTCCGAAAGTATGTT +AAAACTAacttagaaatttgaaactttcagaatatatagaacaaaaatag +agtttcatttttgtagtttacaacttttctgaaaaattaggtcctaggga +gatatgccacgtggaagaggcTTATCATCCAGCCAGTGACCCACACTTCC +ATGTGTCATATCTTCTCAGGAATTGATTTTACaacaaagttgtcaactac +aaaaaggaaaccctatttttgtttcatatactctgaaattttcagatttg +tatAGTAGTGGAAAAATGCTTTTTAGCGCCCCAAAGTAAgcatgttgaaa +aattgagaatatgGTTTTTGATGCACTGAAAAGCATTTTCAGCATTGTCg +gatttattcgaaaaaattcaaaaaacactaAACGAAAccagaacttcatt +tttgtagttgacaatttttctgaaaaatcaggtcCTAGGGAGATATGCCA +TGTGGAAGAGGCTCTCCAGTCCAGCGCGCACTAGAGGCGGCGGCGCCAAG +AGATGTCTTTACTTCCACGTGGTATATCTCTCTAgaacctaatttttcaa +caaaattgtcaactacaaaaagaaagctctatttttgtttcatataCTCT +GAAATACAagttcgctctattgataatcgCAGTCCGTTTACTCACAATCC +GCCTTTATCGGTTGACATGCCGTATCTGCTGGTCCCAATTTCAACCTAGG +ATTCGCACAGTTACACTTGGCTACCGTATCCCGTTGTTTGCATCCGTTGA +AGCATGTTTCCAAGGTGTAGGTGAAGTTCTGGAATAtgggacatctggac +acaaCAGATACACAGACATAGTACCTTGTAATAGTCAGAAGTGTCAGGCT +CCCGACTGACACACTTCCCGTAAGGACGTTTGGCACGGACATGTTGGGTC +TagaaattgtagtttgtagtttcagAGCCTTCTGGAACCTTCTAGAGTGT +TACCAATGTCACTGAAACAGCACTTTCGTATCCTACGCCTGCATCGATTC +CATTTGAATCTAATCCTGGCTCATTTCCTCTTGAATTGACTGCAACTCGA +GCTCCAGCCAGTTTGTGGTTGGCAAAAAGTCTGTAGTTCCACTGGTTTTG +GTTTGCTGGAAGAGAAAACGATTTCTTAGACTTCCTAGGCCACCCTACCG +TAACCGTCAACATCAGTTTTAAACCGAATTGAATACCTTCACGGCTTACA +GAGTAGTTTAGTGAGGCGTCCTCGTTGAACGAGTAGCAAGCGCCGTAGAC +AGGATcaatgaactttttgaaatcagatcTGAAGGAGAATATAGgataga +ctacaaactacaacttACTCAGCACACGGGATTCCAGCAAAACTACAATC +CTGGACCAGATCGGAATAGGTGTATAGTGCTGGCGCTTTATTAGTGTCGG +ATATCAAATTAGCTTCCAAAACCAATGCATCAGCAGCGCGAGCATCCAAA +TCGTATTCTTCAGTTTGTTCTTCCTAAAaatcttcttgttcttcctaAAA +ATCGGCAAATCCTCAACTTcaaacccatatatctcattttctgtaaaaga +tatcaaaaacctgtaaactaacaaagtgtttattataatattaaaaatat +tttgtcagtttatcactttttgatatctcttgcaggaaccgagataaatt +ggcttaaagttaagGAGAGGTCATTTATACggtagctcaattatctcaat +ttatGTAAGagaaacaaacattttgtcaactaataaaatgtttggcaTAA +AATCattgacattttatcagttgacaatttttcgatatcttcaataggaa +ctgagataattgagctcaaagtatatATTAGCGGACATGTTCTTGAGTTC +AAGGGTGATGGGCAAGCCCACCGGCTAGGGACCAGAAAGCCCACTAGCCT +GTACGCCCTCTCCACCATCTCAGCCTGTGGTCGCCGTGGTGTGGTGGCTA +GCGCGCTAGACTTTTGCACACAACATGCGAGTTCGAATCCAGTAGAGTGC +AAATCcttatttggtttttgaaaacttgattttagCAAACGCGCTCCCCT +GGACAGTTTTAGAAACTTCAAACTACCATTTTGACCTACATAAAGACCCC +ATTTATCAGTTCCATAGGTGCCAGCGACAGCATTCGAATAAGCAGTCATC +AGACTATTGACTCCTTGAAATGCAGTGTTCGATTTGACTACCGTATACTT +GTAGGGATTCATATTGCATACAGTAACAActggaaaaatctggaaaactt +tttttctgatttccaaaaatctctgaaaattactttACCTGTTTTTCAAA +GAGAATCTCGGTGTTGACCGTCGCTGGataggagaaaaatttggCGATTA +AAATGTAGAGTTCATAGGCAAACATGCCAAGGACAAACACAAAAATGACA +ATCCAGAAGATTCgggaaatctggaattttcagaaatccagaaattcaaa +aattcagaaattcagaaattcagaaattcagaaattcaaaaattcagaat +tttcagaaatctggaaattcaaaaattcagaaattcagaaattcagaaat +tcagaaattcagaaattcagaaattcaaaagctcagaaattcagaaattc +aaaaattcagaattttcagaaatccagaaattcaaaaattcagaaattca +gaaattccaaaattcagaaattcagaaattcaaaaattcagaaattcaaa +aattcagaaattcagaaattcaaaaattcagaattttagaaattcagaaa +ttcagaaattcagaaattcagaaattcagaaattcaaaaattccaaaatt +cagaaattcagaaattcagaaattcagaaattcagaaattccaaaattca +gaaattcagaaattccaaaattcagaaattcagaaattccaaaattcaga +aattcagaaattccaaaattcagaaattcagaaattcagaaattcagaaa +ttcagaaattcagaaattcagaaattcagaaattcagacggcctaacttt +cccatttttggggttttctaggccaccaccgtATTCCCTCAATACGGTCC +CCTTCGTTCCTCAATTTCTCACCTTAGAAGAACAACTTGTTTATCTCTGT +TTCGGAATGACAtcattccgaattttcttatcttctctctctctctctct +ctctctctctctctctctctcacctTATTATTTGCATTTGCCACGTGCGG +AACGAcagctacagtactccaattggaaaaatctttaaaaatctgaacgA +ATCCGCCGCCTctcatttttggaagaaagtgaaaaaaatggaagatttCG +AAGACTTTTTCTGGTAACCATGGATACCAAGGATTGgaggaattttaaat +tttttggagaagagcatttcattgtttcagaaacatgttttttgctcttt +tgcttcttttctttcggggaattttttgaaaaggagcAATATTGTGACTT +GGGGACTAGAAATGAGGGAATcggggttttctaggtcaccgaATCTCCAG +AATTCGAAGATTTTTAATTTGGAGATCAATACgctaaaaatctgaagaaa +tgTTGCTTTTTTGTCTGAACAACTTTAggatattccagaaaaattgcata +atctgaaattaaaaaattggtgaaatatacaaaatttctagaattcagaa +tttcagagccagaatttctgaaattctgaaattctgagattctaagattc +tgaaattctgaaattctaaaattctggaattctgaaattctgaatttctg +agattctaagattctgagattttgaaatcctgaaattctgatgattatgg +aactagaaattctgagattatgaaattctgaaacctctgaaattctgaaa +ttctaaaaattccgatcctttttcgaaattttaagcttCTGGAAGATTTT +AGGATAGTTTTCCTATTTTATTGCTCTTTGTTTCCCGAACTTCcataacc +tttttttcagaacttgcttcatttttttttctggtcaTTTTTAGATCACC +TTGCCTCCCCATCctaaaaatatacaaaatatCACATCACCAAAAAACGG +ATCCCTTTTTCGTCTATATTTTGTTCagacaacaacaaaaaactttgaCG +CTGACAACGGTGAGCAGCTGAATCTCTCTTAGGTGTTAAGGATTAGATGG +GGGATTTGAAATCCCCggattttccccttttttcttttggctTATACGTA +TACTGAAAATCGTATAGTTGAGGAAatgaaggaaaagagagagagagaga +gagagagagagagagagagagagagagagagagagagagaaatagaaATA +TCCCAGAAATAGGTAGCTGGAACACAACGAAATTTTCTATGAGTTAGAAG +TACCGTACCAaacaaaatgtgaaaaaatacaGCCCACCCGCACCTacaac +tttgatctcaattatctcgattcctgtaaaagttattaaaaatgtgtcaa +ctgataaaatatttttgatattatgatgaatctTCTAAgagttgacaaaa +tgttgacaactttcataggaatcgagataatcaagctcaaagtgggcggt +GTGGGTggggttctattagaggaattGCTGTACCCAAAGTTGACTATCTT +CCACTAAAATagcaatttcgaaatttctttgtTGGTTATTACTGtactag +attttttcagaagttttaaaacGGTTACTGTAATCATTCCCTAAATTTTG +GCTAATTTTAAGTGGCTAACAAAGTCTGAAAAAGGATAAAACCAAAAGAA +ATAtatggaaaatttggtttttgaacaaattgtattttttatttctcata +ataatacaaatattttatcagtagacaaaattttagtatctttcacagga +accgagataattgagcttcaaGTTGACGGTGTGGGTGCGGTTCTGTTAGA +GCAAGTACAGTAGTCAAACTTGCAGTCCTACAAAAgttctccagaatttt +tcggcttgcttgaaaattttaaggaatactaaacaaaagcttcatttttg +tagttgacaacttttttgccaattttcgtTCTGATGAGATATACCATACC +ATGCCGTTTGTaataaaaaaagtgtcaaagtCTCATATCTCGCTTTGCTA +agtttgttcaaaaaagaaacaacttacaaaaatgaagatctaTTCTTGTT +TATTGtgctctggaattttctgaaaaatcggaaaattcaatttctggaCT +ACTTTTGTAGAACTTTGAATTTGACTAATTCCAattgaaaatgccaaaaa +tgtaGTTAACCCTCAAAATCGAGGGGGCCTATCCTTATCGAACGGGCTCC +GTGTCACTTCaaaaccgcgacgtttcgaaaccggtcatttcgaaaccgcg +aaaTTTGCACgctgcaattttttctttaatttaagacttcaaaatttcct +agtttcaatttcatttttacgtGACCGTGTTTGTTTttcggtttcgaagt +gtcgcggtttcgaaatgaccggtttcgaagtgtcgcagaGCCATTGAACT +CACTgaagtgaaatttttgagagtttcaaCCTCCTGAAACATTCTTGAAT +TTAGTAGTATCCACTACTTCAATCCACTTCATTATTACATCGAATTAATG +CTAGAGCGCACTTTCATGTCCCTCAACCAGTCGTTTTTCCTTACCTCTCC +CCTTCCTTTTTTCCCCCTCCCAGATGACGTCACCCATCTGTCCACCCTTC +TAACGGTcccccccACCATCTGCATGGTGTCCTCGGGGGTGAACAGCTGC +ACATTTATTGTTCCCTTCTATTCCCCCCTCCTCGGTCATCGCGGTTTTAT +CCCCGCCGTCCATTTGACCATTCTTTGCGTCtcttccctctctctctctc +tctctctctctctctctctctctctctctctctctctttctctctctctc +tctcttctttttcttctaggCGAAAGAGGTCACATGGAAGAGaagaggat +gatgatgatgatgatggtgggGTGAGAATAGAGTGGTGGTCTAGAGGAAG +AGGTCTACAATAACGGacaggaaaaatggaattgatGGGTTTTGCGGTGG +TGCGCGAGTAACCATGATAACTTATCAATGGAGCGAAGGTGCTACAGAAC +CTCTGGAGCTTTAATCCTGGAAGGGAGTGTGTTGTCAACGGAGCGCACTT +GCTGTGGACCCAAAAACAGCTGGAAGTGTTTCATCGGGAAATGAATTATT +CTTTAAGGTCAACTTCCTAAAATTATTATAGTTCTAgtgactctgaaaat +ctgaaacccTGTCATATATGACATTTTCGGAATCCTTCAAGAATTTAGTA +GGATTTTTCTCAGATCTGCACAGAGAAGATTTTGGAGGAACTAATTTAGG +AAATATCTAAATCTGCAGAATGAGGAGATTTAATGAGATTTATGAGCCGC +GTTATTATTTATgagttattttgaaaatttagaggATTCAAATTTTAACC +TTTTGGGCTTTAAATAAGAGGGGACCTGAAAAACGGGAGATGCCGTGTCG +CAACCagacaccccccccccccccctcaacTTTCATTCCATTTATAaatg +ggtcaaagttaaagggCTTCTTGGTCCTTCTGATTCtgtgaatctcagaa +tttccaaaccTCATAAActaattcctagatttttgcAACTTCAGAGatac +agattttcagatttttcagaaattaagaatttccaacaaaaattgaaatt +cacaaGTTCGATCTTTCCTGTggctttttcattttttttttgtttttttt +tctgaaaatttttttaaaaaatcttaaattttcaaactttttattaataa +attaagtgaattatttcgaaaaactgaatagacacaaagagaaaaaaaaa +cgaaaactaaaaacggaaaaaagaaCATGTACTGTATATACAAATATGAA +TGGGTTTtgggcgggaatttgaatttttttttttcgaaattcatatTCTT +ccgaaattaacaaaaataaCTGGGCGACTGGGACATACAGGGACTGACTG +AGAatggaaagttctggaaatttccagaaaaatgaaaaaaaaagaaagag +ataaTGATAAAATGAAAGAGATTTTAGGAGAAAAGTGGTGGGTTCCcgta +gtttttttaaaggaaaaataaaGTATTTTTTGGATGATGGGATTGGGGGC +Ggagcctttttttttgagacaattttttttcgaaaatttttttctaccag +taatttctttttaaaagtgTGAGTGGGGTGTTTGAAGTATTATATGAATC +GATAAGGAAAGTGAAAGGAAACATAGGAGCCTAGTAATTAAGTCAAAATA +GTGCCTAAAAAGACGACAGAAAATTGTGGAGATTTTCGcctcgattttca +gatcttgATACGCTTCTGGAACGCTACATTGAAGTCGTCGAAGAGTTCGG +TGGAGCGACGTTTCTTTTTGTTAGCATGACATTCTCCAGTTGCCACGTCG +AGATCTGTCAGCTCATGGGTGTCATGGAGTGGTTCCGGAGAAGTGGatgt +ctgaaattatgatctttgaaattttttagaattcaaaattttctgccTCC +CATCCTCTGGTTCAGGCGCGATCTTATCTATGACGTAGACGCCTTCCGTG +CCTCACATGACATCTGCACGCGTGGCCTACTAGCTAGCAGCGCTGGTTTC +GATGAGAGGGTTCGCTGGTTCAAGCCCCCTGGCTGCCTATTCCTTTTTTG +CTTCTATTTTAGAATGCCCAACTCACAAAGACTGGCTCCACGGATGCTCT +GTTGGCCAGGAAGTAGTCGTCTCCCGGGAAATAGGTCGCCGGTCCTCCTG +GATTCGCCGACGTGTACGCATCGTAGCGAGACGGCTCACGAACGCATCCG +GAAATGCTTGCCAGCGGATCGGAAGCCATTGGAAGATCTCCTTCGGTCGC +CGACTCGGACATCGAGCTACCACCACCATACATATCAAACGATCCATAGC +CGGAAGAGTAGGATGGTGGAGACATGTCGAATGGATTGTAGGATACTGTA +GACATGGATCCGAAGCCTCCGCTCAGCTCGTTGACCGGATACGGTTGATG +CAGCCAAATATCATTGTGCATCATTTGATGGTGATGGTGGTCGTAGTTGT +TGGTGAGGTCTTCCAGACGGAACTCGTCAATGTCTTCCTCGAAAAATGCC +ACTTCAGACATATCGTAATCGTCGTACTCCTCGTCAGACGATGAGGCCAT +GTCTTGTTCTCGAGGCGACGTTGgcttttttggcattttgaaGAGGTCCG +ATACAAAGTTTTTGATGAGTACTCTGGAAAGATTCCAAGGTTCTAGAGGG +GCTGAGGGAAAATACTCTAACACCATTCCTTCTAAGTTTGAGTTAATTTA +TCTAGACtcctgtcaaaggtatcaaaaagtgatcaactgataaaatgttt +accataattcAAGAAAccttttattagttgacaattttctgatatctcta +acaggaaacaagataaattagctcaaactaaACCATCCTAGAACCCCCAA +TACCAACTACAGTATCACGAACCTCTTCCTCATGGCTCTTCCTCCACACC +CGGCTCGCTTCTTCTCCGACTTATCACTGCATTTGTGAAGTGCCACGTTG +CACAAATGGCCGAAGATCTCCTCTGTCAGATCGTTCAGCTTGTACGTCTT +GTTCATCATTATATCTGGAAGGATTCGAGAAATTAGAGAtagaaacaaga +agaagaagaaggacataagttcagaagacgttatgATTTTTGATACTCTT +CAAGGGGAAGTGTACTTCGGAAGGCAGTAGTTACAGCAAGGGCGCGTCAG +AGAAGGTGACTTATCGCTACAGTACCCCACGCCAAAATTGAGAGAACGCG +CGCGCGCTTATCACGGGACTTTCACACCTTGTAAAAAGTGTGCGCGCGTG +ACCGACTGGCTAGAAGGCTCGTTTTGGTGCGAGAGGCCAGGGGTTCGATT +CCCAGCTAGGGTAAAAGcctttttgcttttgttttATAGCTTCTAGTGGG +GTGTAGGATGTCGTAGGAATGGATCCAATGTCTAGGGGCCCCGTTTTAGG +CCTAAAGATTCTGTTTTTCGCTTTTCTAGGCCTAATGGATCTAGTTTGAG +ACACTAGCCTGTATGTCTAAAGCTAGCCTTTATGTCTAAAGCTAGGCTGG +TCCTTAACGATAGATTTTCTAAACCTTATGGCCTAAGCTAGCTTTCGATC +TTAAGACCAAGACCTAGGCTACCGTATTATTTATCTAGGACTAATGCATC +TAGGTAGAAGGCTAGGCCGAATCTAGCCTTCAATGTTAAGATCAAGACCT +AGGCTACCGTAGCTGCTCCCCATACATTCCTGGTCTTCGAAAATAACTTT +TGTGTCTATTTCCGTTCTTCGTTCCCACACTCTGACTGGACCTAGACTCT +AAAGAACACGCACACAATTTGTATCATTTCCTCTCgggtttattttttct +cctaaCCAATTGGTCATTTTGTGATGTTTGCATGTGCTGTCTCGCCACAC +TCACACAAAAAATAACTATGTGTCTGGAGAGATAAATGAATGCACTTTGC +TCTCTCATTCTACCCgtgtgtctctctctctctctcaacaATGAGATGGT +GATGATGATGTGTTTTTTCGCGTATCGCGCCCCTATAGGAGGCCCCCGTG +AGgcagcaagaagaagaagaagaagaaagaattgaaagaagCGGCGCACA +CAAACCCAACACAGCCCAAACTGCGCCCCATAGTGAAAAagcgaaagaag +aagaagaagggagggGGCTGTCCTATACGCTGTGCCCCGCGGGCTGCTGT +GGCTGCTATAGCGAGCGAGCGCGCGCGCACAAGGCCAcccctctccccct +tctttctctcgtcttgtcctctctcgcttctctctgcattctctaattca +ctatctccttaccccctcttctctggcctctcctctcCGTCACATGATGT +CTTTGTAATGACGAGTGGTGCTCTCCTCGTTCCCAACACTATTTCGCATC +CATACATACACATCGGGCGAAGCGGCAACCCGACGGCGGCCCAACCAACC +AACCAACACAGCCTTCTTCCCTTCTCTTCCCTTCAATTTGATtcgaaaga +aggagaagaagaaggcaatGGAAAGAAGGGTTTTGGCTGGGCTGGTGGGG +GAAACAAAGTCTAAAAGGTTCGCCGATGTATGTTCATCTTCTTGTTCAGG +ACCAAATGGCCGAGGATTTGCAATCGGCGGCCGGGAGACGGGTTGAACGA +AAAAAGTGTATCTTTTTactcgaaaattgagagaacACCCCGGCATGTTT +ATCATCATCGATGGGGGAAAACCCCCCGTGTCCTATTAATAGACGACAGA +cctggaaatgagaaaaaaacggacGGGAGGTCAAAATGTCTACTATCAGT +TCGGGCGGTACCTGAAATgtctgtttaaaaaaaagcggaACACAAAAGAA +AAGTAACACTTTATTGGATCGACGAAGAAATGGAATCTGGAACTTGACGG +TTATGACCTactgtactttgagctcaattatctgaatatctatgagagat +atcaaaaattgctaaactacaaaaaattagtGGTATTAtgaagaacattt +tattagttgaaagatttttgatatctcttaaaggaactgatatgaattgg +ctcaaagttggaagtcCATTTTATTAAGGCAATCTATGAATTTCAGGATT +ACAAAGActcagaatttggaattcttagattctgcaGTCTTTTAGAATGT +TTCTGCAATTACGGTATGTGAAAGGGCCAAATCTTGatagccattttcag +caaaacaaTCGTTTTCTAACATTTTGACCAAGTCTAAAACGGACCCATGT +CTTAAAGGGTCTTTCAAAAGTTGGCAGGTCAAATTTTAGGCGTATAGTTC +AACTCAGTTTGAATCTcctttttgttgaaaatttaaaatttaaaattttt +gggatttcatgGCCTAGTTTATGTCATCTAAACAAGAGGTTTTAGGTTAG +AACTTCCTTtaggaactttcaaatttctcataaaTCTGTCTGTGTGTTGG +TTTGTACGGATTTCCTCTttcttattttaaaaattatttgctTCTAGTTG +GTTTGAAGCTTAACcaacttttaaatttcttcttctgttaAAGTCTGTCG +GTGAGTCTGTGTATCCGGATGTCCAAGTTTTtcgtttggaatttttgaag +aatgccTTTGGGTTCCTGTCTGCATTTCGACGTGATGGTGTTTGCGGAAA +ttagagctacagtaattcacAGGTCAGAATACACACGAAAACATCGCAAT +GAGAAAGGAAACTTGCTCCtacagaattcagaaattttccaaattttagg +atttttaggatttctagaatttctagggattttggatttctcttggagtt +ttagattctagattttcaaatttttcgaaaatcttcagaatctcaaagtc +tgtttgtccagatgtcccaTGTTCTcgactctgaaatttttgattttaga +aaactcaaaaattcgcctattcttccatttttgaattttcctatcaacct +gaaaattttgaatttttcgaattaccgtagaacctgtattagaagggccc +ctctagtagaagggcccctctcatagaagggccctctgtgaggggcttgg +aaaaatagaagggccccctgtaatagaagggccggcccttctaatacagg +ttttacggtaagtgcTTTCTAAACCAcccattccattttttttcagctcc +gcccaaaaaaacaattttttcgatttcataaattttttcacttttcggCA +GAGGACGCAGGTGGTGTCTAGATTGCCACAGCCTCTCTCCGCTAGTACTT +GTTGTTGACTcaccaaaagaaaaaaagaatttcgcAATAtctattttaca +aaaaaaatattcggtgtgtccggatgtccggaTTGCGTTTCTTCACAGCT +ATAGTAGTCTGGAGCatgcctgaaaatatttttccatcGCGAAGATTGCC +TCAAAACATtcgtacagtaatcccagagCTCTTTTGGATGAGTCATACGG +TAgatggtgatgatgatgataagaggaaaatggaagaaagagagtatgga +aaaatgagagagtctagagaaacagagagtgtattggagcagaagaagaa +gaacgtcATCAGATTGtcttatcaaaaatgaaaaaaaaacgcgggggaag +aaaaaaatgtggaggaaaattttgaaatttagagaactaggaggaaaagg +gaaaatgcaaaactatgaacggaaaaaaaGTAGTGTCCTTGGAAAAACGC +CTTTTGGTGGGATTGTGAAATTGGATATGTTATTTTTGGCAAAATAATAA +ATGTGTCTAATAACGATTTTTGGtcattctaaattttgaaaaaaagtgga +atttgAAACCAGACGGAGTCCTAACTTTGACCACATttatctaggttact +gtaaaagatatcaaaaagttgtcaactaataaaatgtttgtgatactatg +ataaacattttatcagttgatcactttttgatatcttttatgaaaatcga +gaaaaatcagCTTAAATTTTGGGACGGACTTCTACGCTAAGATAGGGTAG +AAAGAACTCCTAGCTTTGGCCCAATTTATCCAGGTCCctgaaagagatat +caaaaagtgatgaactaacaaaatgtttgtgaaaaaatgataaacatttt +atcagttgactacttttttatatctatcacagaaagagagataaattggc +ttaaagtaaAAGGACTCTTAAACAGACTAACTTTTaggatttactttttt +tttttgaaaacggcAAATTTTACATGATCTACAAAAGCagttaaaactat +ttttatttttctgaaatttttagagtatactaaacaaaaatacatAGTCC +TTCAAGTTtatagttgaccacttttttgtgttatttcaTCTAAATGAGAT +ATGGCGCAGAGAAGATGTCTGACGCCTCTacttggcaccgtgccaagaAG +GAACAAGAATGTTGGCACGGTGCCAGGacctcaaaaaaatgttgctctat +ttttattttcttttagaaaggaaaatctgaacttttatgaggaatagaaa +tttcagaaaaaatgaaaaattgaaatttccaaaaaaaaaactataggAGG +ATTTTCCTAAAATCTGTCCGTTTGTATTTCCTAATATCCGGTTGTCccta +aactaaaaaaattgttctcaaaaattctgatttgtcaaaaaaaaggagaa +gaatgtTCTATTTAGGACGGAAACAAGAAATCAgagagacacaaaaaaaa +gcaaaaacgtgcaataagaaaattagaagatgaaaaaagagaaataacga +aaaagagaaacaaaacatagcgtttttttttcgacgggaatgaaaaatga +agaaaatggagaaaacgaaaaaaagtgtgaaactttttttttgattggtg +ggaatttttttgtcttgaGTGGGAGgaaaaggaagaggaaaatGATGAAC +TGGAGGTTTTGAAAAGGAATCAcacgaatttgaaaatttgagttcccGCC +AAGATTCCACGGGActctaatttgaaaattttcgaaaatttgaaaattca +aaatatgaaatattttctgtgtcaaatgacagaaaaattAATCAATCTTC +GGCTCCGaatgttgttgttgttgtaaAAGATACGCAGCGAAATTTGAAGC +GGAGCCATTTGATGCTCAGTTaacggttttttttatttgtgaaGAAATAT +TATGACGTATAGATGAAAGCAGCCctggaaatctagaatttcatgaaatc +gaaaaaaaaaattaccaaaaaagcTTCCTGTCTATTCTATTCCTGGAATA +AAAGGGTTTCCCAATTTTGACCCAACTTATCTCGATTCGCAttggagata +tcaaaaagttatcagctcataaaatgtttatcatgatatcacaaacattt +tatcagttgacaactttttgatatctcttacatgaaccgagataaattgg +gccAAAGCTAAAAGGTCTTCTTACCCTATCTTTGCGTAGAAGTCATCCCC +CAATTtaagctgaattatctcaatgctcataagagatatgaaaaaattgt +caactaacaaaatgtttaccatattATCATAAATATATTGTaagtttatc +attttttgacaactcttacaggaacctagataaattgggtcaaaactAGG +AGGTTCTTCTACCCTACCTTAGCATAGAAGCCTCttcctaactttgagcc +aacttatctcgattctcataagagatatcaaaaagttgtcaactaacaaa +atgtttgtgatattatgataaacaatttatctgttgacacatttttgata +tctttcacaaaaagcaagataatttggctcaaagttgagggaCCTTTCTG +TTACATCGGGTTAAAATGAACCTTCTAAATTTAAATatgaatctcaggat +ttcaaaatctcagaattttgaaattttgtattctCACTTCcctgaaaaat +atggatttaGCCAAGAGAATTGGAAAGAAAAGTGAAATGACTAGaagaaa +gaaacgaaaagCCAATAGCTATGGAGACCCgtcagaaaaccaaatacgCA +AACTTTTCACATCATCTCAAACAAAACACACAAATACACAAAAAGGGAAA +GAACTAGAGGaaatttcatgagaaaaatacaatttgttcaaaaaccaaat +tttccataTATTTCTTTTGGCttagacattttcagactttgttAGCCACT +GAAATTAGCCAAAATTTAGGGAATGATTACAGTAACCgttttaaaacttc +tgaaaaaatctagtaCAGTAATAACCAacaaagaaatttcgaaattgctA +TTTTAGTGGAAGATAGTCAACTTTGGGTACAGCaattcctctaatagaac +cccACCCACaccgcccactttgagcttgattatctcgattcctatgaaag +ttgtcaacattttgtcaactttTAGAagattcatcataatatcaaaaata +ttttatcagttgacacatttttaataacttttacagaaaccgagatagtt +gaactcaaagttgatggtgtGGGTGtgggttctattagagggaatacggt +agttaAACCTGAAGTCCTACAAAAGTGctccagaatttttagatttgtcg +gaaaatttcaggttacactaaacaaaaatagagcttcatttttgtattaa +acatatttttgtgtAGTCACTGGTTACATTGGATGAAAGACATGGCATCC +AAAAATGCCGGAATTCCATATGAAATTGTTTCAGACTGTCTTTTCGGGGG +AGGCGGGGAGATCCTTTCTACGAGTGcatgtacaaaaaagttgctaatTA +CAAACATAGAGTACTGTAATTGGTTAGTGATATCTGCAACTTTCAATAGA +GCAATTACTAAGAAACCCCAACCTCAATTGTCCTCTAGATGCATTCTCAG +GTTCGGCTCCTTTTTGCATAATTgcgcctttgccgggccttcgcggaatc +tgccatagtttcttagaaaatcaatatttttaaattaatttaattagata +tgatagaacttgtCGAATGTTAcgaaatgatactatttggagtactgtgt +cttgtctatgaacaaagttacaaacgAGAAACAGAGGCCCGGCCACTTta +tgacttgtaactttgttcatagacaagatacaatattcaaaacaatatca +ttttgtagcactcGTTGAGTTTTATCATATCTATTTTAGTCATGTCAAAA +ATATTGCTTCtcaaagaaactatggcaaggCCCGCGAAGGGCCCGGCAAA +TGCGCGGTCACAAgtatgcatttttgaaatcttcatgCTTTTCTGTGTGA +ATAAAAGAACGAAAGTTGATTGATGTTATAATAaaatatataggctcaaa +ttaACCTAAACAAATACAAATTTCCCGGGACGAACTTCGAAATAATATGA +TAcaaatttgaagaaacaaAGCTATTTTAGGAATCCAGACGAGTTTAAAT +ATAATGAAAATTGGGTGGTAGtttagagccaaaaatcgctaaaacATTCA +AAAGATAATATGATCTGGACcttaaaattggaaattccaaaacagtGCCA +AACTAAAAAGAAATGTGCTAACCTGAACACACTGACTGACACGTACATAT +CAATACACCATGTTATAAAAATGTGGTGGTTTATTGATGGGGGGTTTTAG +AGGGAATAGAGAACGAGTGAAttggagagagaaagagaaaaagaaaaggt +tcAATAATGGCCGATTGTGCAGTTTTATTACTTTGGgtgaaatggagaaa +aagggaatgaaactcgaaaaaaaaaacaaaaaaaaggaaaaaagaactaa +aaactacgaaatcaggggaaaaTACTTTTGAGATCATGCTCCTTTAAATA +CCTACTGTAGAATCAAAGGAACATGATTAGAAGTGATAAGGTAGCGGCAC +ATCCCGTGAGATACCCGAAAATGCGAGATAAAAATTCGCTTAACTATCTC +GCTTCCcattaaagatatcaaaaatttgtcaactgataaaatgttttttc +ataaaatcattaagattttatcagttgacaattttttcatatctcttggA +GGAACCAAGGAGCTTAAAGTAAAGTTGACATTTTGCAGGTCATTTAAACA +GTATCAGAAGACAGAAAATTTCGTATTCAACAAAAGTGGTTGTTCAACAG +AGCGCGTTTTCTTAGAAGATTTAGTCATTTTTTAGATTaggtttttgaag +aatttgaacaaaatacAATCGCTTGCGAGTGAGCTTGGCgttctctggaa +aatttcagatcaagaattcgaaaaaaaaatctgactaAGCAAGCCTAGaa +atttcctgtaaaagtcTGACATGTACAGAAAAAAGAGTGAGTGAGTGAca +ccgaaaaaaagtgaacacGAAAAAGAAGTGGTAGTTCGGTTGGAAAACAT +AAATATATACATAGCGAAGAGGACAGACAACCCTTTCTTCCATCCCATAC +TGACACATAGACATATAACATAATACATATGAACAcacaaaagaaaataa +atttaggcagacagaagaagaagaataaatgTGGAAAAGAATGGAGGAAA +GGGCAGAACAAATGAGAAATTGGAGGAGGAGAATAAGAATTGCTAGTTTT +GGctatttttgggaaaaggaGGAGATGGTGTACTTTGTGTTGTTGATTGA +GAAGATTCTCGAATCGGCTGCAAAATTGTCTAAATGACCTAACACTTTGA +ACAAGTTTTGGGAGTGCTGATTTGAGACAATTTAAGACAGCTAAAAATAG +TAACAACGAGTTTTCCTTCCATAGAAATCAGCTTCTAGATATTACAGTAA +ACGTATATAGagggcaaataattcggagggtacaaaaatttaggaatcat +tggggtacaaagcaatttaggggtacaaaatcttcGATTCGGAggtacaa +aatacctgaaaaaggCTTAGTTTTGTACTCCCGAATTGTGAATTTCGTAT +ccctaaatcactttgtaccccattgtacccccgaattatTGTACCATCAG +AATTATGTGCCTATAGAGTCATGTTCGATGTATATTCgctgagtagcgac +tcaacgACCCAACTAGAGTGATACGAAACACACATTTCTAGTAGTTTAGC +ACATTTTCAAGAGAATTCTGAATACATAATTTTCCCCGAATTGGAGAAAA +TAAATGCGTAGGCTGGTGACGAGAACAAGAACCGCTCGTTAGCGATTTGA +ACAGAAAGACACTACCTGCATATTTTGTGTACTGGAGATTAGATTATGAA +TGCAGAGGGTATTCAAAATAAATGTAGATTGAGAAGGAGTACATAGGAGG +AGAGGAtcgaagagaagaagaggaaatgaACAGGTAACAATTACAATTTA +CTTATCTTCGGACCCCAAAGAAGGCTCTAATAGAACACAACTCTTATGAA +cacaattatcttgattcctgtgacagatatcagatttttgtctactaata +aaattttgggtgataatatgataaacattttattagttggcaaatTCGAA +TTATCTTTCAAGgaaagcgagataattaagatttttgaaaaagctgaATT +CTCactttgacgtcttctgaagacatCTAGAAACAAAAAGTCACCGCCAA +CAGAAAGGTTTACGTCATCAAAGATGACATATGGACAATTTGAGTAGTGA +GAAAGGGGAGTATGAAAATTGGTTCCATTCGGCAtcttttctgaactttt +agcTGAGCAAACCAAACTGCAAACTTGACATTAGCACACAAGAATATCAA +AATCCATTAATCCAGAAAAACACAACTCCTCTaatggattttcagagatt +tcggCTAAATGTATCTTGTCATACAACACTAGAATTAATCTATCTTGGTC +AAGATTAAGGATTGGGGAGGTACGCAGCGAAATCAAACTCTACGTTTAAT +ACTCAGTTCCTTATTTTGTGAATGTCGCTtagtgaatctgaaaatgcagT +TAAAGGCGCAGCATGGAAAAACCATGGATACAATAATTATTGCATACAGT +AACAGGAAGATagttaatttttagaaagttttgaaagtagTCCAGAATGT +TTcgattattctgaaaatgttgaaattgactaaaaatacGGTAACTCGCT +CTTGCGCCTTTAAGTGTTCCTTTAATGTTACTCTCGCTCTCAGCGTATAT +TGATTTCGAACTAgtcagaaaaatctagaacatcacatcatttttctcaa +caacaaaacacacaaaatgaaagaaattttctgggtgaagaagaagaaaa +aagaagaagtgagtgttcttttttcattgtgccattttccaaattggtgg +aaaaaagaagaaaaagaggaaacaaaaTGAAGTCCACACACATGTGATAC +atcaattagaaaaatgagcattcggggaaggaggagaaggaaaAGTAATG +TTTGATTTTATaaataaaggaaagaagagagaaaagagcagttgaaaaga 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2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ + +#pragma once + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ +/// \defgroup cudaextender CUDA Extender package +/// Base docs for the cudaextender package +/// \{ + +/// CUDA Extender status type +enum StatusType +{ + success = 0, + invalid_operation = 1, + invalid_input = 2, + generic_error +}; + +/// Extension types +/// ungapped_xdrop performs ungapped extension with an x-drop threshold +/// +enum ExtensionType +{ + ungapped_xdrop = 0, +}; + +/// Initialize CUDA Extender context. +StatusType Init(); + +/// \} +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/include/claraparabricks/genomeworks/cudaextender/extender.hpp b/cudaextender/include/claraparabricks/genomeworks/cudaextender/extender.hpp new file mode 100644 index 000000000..ee4fcc05e --- /dev/null +++ b/cudaextender/include/claraparabricks/genomeworks/cudaextender/extender.hpp @@ -0,0 +1,158 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ + +#pragma once +#include +#include +#include +#include +#include +#include + +namespace claraparabricks +{ +namespace genomeworks +{ +namespace cudaextender +{ + +/// \addtogroup cudaextender +/// \{ + +/// Seed positions in target and query reads +struct SeedPair +{ + /// position of first sketch element in query_read_id_ + position_in_read_t query_position_in_read; + /// position of second sketch element in target_read_id_ + position_in_read_t target_position_in_read; +}; + +/// Segment pairs in target & query reads with associated length & score +struct ScoredSegmentPair +{ + /// seed for the segment + SeedPair seed_pair; + /// length of the segment + int32_t length; + /// score of the segment + int32_t score; +}; + +/// Equality operator for ScoredSegmentPair +__host__ __device__ inline bool operator==(const ScoredSegmentPair& x, const ScoredSegmentPair& y) +{ + return ((x.seed_pair.target_position_in_read == y.seed_pair.target_position_in_read) && (x.seed_pair.query_position_in_read == y.seed_pair.query_position_in_read) && (x.length == y.length) && (x.score == y.score)); +} + +/// CUDA Extender Class +class Extender +{ +public: + /// \brief Virtual destructor for Extender. + virtual ~Extender() = default; + + /// \brief Host pointer API for extension + /// + /// Takes values from host data structures, copies them over to device, + /// launches async extension kernels on specified stream. Filters + /// segments on device based on score_threshold + /// + /// \param[in] h_query Host pointer to encoded query sequence + /// \param[in] query_length Length of query sequence + /// \param[in] h_target Host pointer to encoded target sequence + /// \param[in] target_length Length of target sequence + /// \param[in] score_threshold Score threshold for filtering extended segments + /// \param[in] h_seed_pairs Vector of seed pairs mapping to query and target + /// sequences + /// \return Status of the async extension launch + virtual StatusType extend_async(const int8_t* h_query, int32_t query_length, + const int8_t* h_target, int32_t target_length, + int32_t score_threshold, + const std::vector& h_seed_pairs) = 0; + + /// \brief Device pointer API for extension + /// + /// All inputs to this function are expected to be resident on the device + /// before launch. Output array d_scored_segment_pairs must be pre-allocated on device. + /// Launches async extension kernel. Filters segments on device based on score_threshold. + /// The stream associated with this function call must be synchronized to before accessing + /// any output parameters. + /// + /// \param[in] d_query Device pointer to encoded query sequence + /// \param[in] query_length Length of query sequence + /// \param[in] d_target Device pointer to encoded target sequence + /// \param[in] target_length Length of target sequence + /// \param[in] score_threshold Score threshold for filtering extended segments + /// \param[in] d_seed_pairs Device pointer to array of seed pairs mapping between + /// target and query sequences + /// \param[in] num_seed_pairs Length of d_seed_pairs array + /// \param[out] d_scored_segment_pairs Pointer to a pre-allocated device location for + /// storing extension output + /// \param[out] d_num_scored_segment_pairs Pointer to pre-allocated device location for + /// storing length of extension output + /// \return Status of the async extension launch + virtual StatusType extend_async(const int8_t* d_query, int32_t query_length, + const int8_t* d_target, int32_t target_length, + int32_t score_threshold, const SeedPair* d_seed_pairs, + int32_t num_seed_pairs, ScoredSegmentPair* d_scored_segment_pairs, + int32_t* d_num_scored_segment_pairs) = 0; + + /// \brief Waits for CUDA accelerated extension to finish + /// + /// To be used with the host pointer extend_async API. + /// Blocking call that waits for all the extensions scheduled + /// on the GPU to come to completion. + /// + /// \return Synchronization and memory copy status + virtual StatusType sync() = 0; + + /// \brief Returns the computed scored segment pairs + /// + /// To be used with the host pointer extend_async API. sync() must + /// be called after launching async extension and before calling this function + /// or the returned results will not be valid. + /// + /// \return Vector of Scored Segment Pairs that have a score >= score_threshold + virtual const std::vector& get_scored_segment_pairs() const = 0; + + /// \brief Reset Extender object and free device/host memory + virtual void reset() = 0; +}; + +/// \brief Create Extender object +/// +/// \param h_score_mat Host pointer to scoring matrix for use during extension +/// \param score_mat_dim Dimension of the scoring matrix +/// \param xdrop_threshold Threshold for performing X-Drop +/// \param no_entropy Flag indicating whether to use entropy during extension +/// \param stream CUDA Stream to be used with extension +/// \param device_id GPU to be used for extension +/// \param allocator DeviceAllocator to be used for allocating/freeing memory +/// \param type Type of extension to be performed +/// \return Unique pointer to Extender object. +std::unique_ptr create_extender(const int32_t* h_score_mat, + int32_t score_mat_dim, + int32_t xdrop_threshold, + bool no_entropy, + cudaStream_t stream, + int32_t device_id, + DefaultDeviceAllocator allocator, + ExtensionType type = ExtensionType::ungapped_xdrop); +/// \} +} // namespace cudaextender +} // namespace genomeworks +} // namespace claraparabricks diff --git a/cudaextender/include/claraparabricks/genomeworks/cudaextender/utils.hpp b/cudaextender/include/claraparabricks/genomeworks/cudaextender/utils.hpp new file mode 100644 index 000000000..f99f14483 --- /dev/null +++ b/cudaextender/include/claraparabricks/genomeworks/cudaextender/utils.hpp @@ -0,0 +1,151 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ + +#pragma once +#include +#include + +#include +#include +#include +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ + +/// Sequence encoding scheme: +constexpr int8_t A_NT = 0; +constexpr int8_t C_NT = 1; +constexpr int8_t G_NT = 2; +constexpr int8_t T_NT = 3; +constexpr int8_t L_NT = 4; +constexpr int8_t N_NT = 5; +constexpr int8_t X_NT = 6; +constexpr int8_t E_NT = 7; +constexpr int8_t NUC = 8; +constexpr int8_t NUC2 = NUC * NUC; + +/// \brief Parses seed pairs from a csv file in the following format: +/// target_position_in_read_1, query_position_in_read_1 +/// target_position_in_read_2, query_position_in_read_2 +/// target_position_in_read_n, query_position_in_read_n +/// +/// \param[out] seed_pairs Reference to vector into which parsed seed pairs are saved +/// \param[in] filepath Reference to the string containing the path of the seed pairs csv +inline void parse_seed_pairs(const std::string& filepath, std::vector& seed_pairs) +{ + std::ifstream seed_pairs_file(filepath); + if (!seed_pairs_file.is_open()) + throw std::runtime_error("Cannot open file"); + if (seed_pairs_file.good()) + { + std::string line; + while (std::getline(seed_pairs_file, line, ',')) + { + SeedPair seed_pair; + seed_pair.target_position_in_read = std::atoi(line.c_str()); + std::getline(seed_pairs_file, line); // Get the next value + seed_pair.query_position_in_read = std::atoi(line.c_str()); + seed_pairs.push_back(seed_pair); + } + } +} + +/// \brief Parses scored segment pairs from a csv file in the following format: +/// target_position_in_read_1, query_position_in_read_1, length_1, score_1 +/// target_position_in_read_2, query_position_in_read_2, length_2, score_2 +/// target_position_in_read_n, query_position_in_read_n, length_n, score_n +/// +/// \param[out] scored_segment_pairs Reference to vector into which parsed scored segment pairs are saved +/// \param[in] filepath Reference to the string containing the path of the scored segment pairs csv +inline void parse_scored_segment_pairs(const std::string& filepath, std::vector& scored_segment_pairs) +{ + std::ifstream scored_segment_pairs_file(filepath); + if (!scored_segment_pairs_file.is_open()) + throw std::runtime_error("Cannot open file"); + if (scored_segment_pairs_file.good()) + { + std::string line; + while (std::getline(scored_segment_pairs_file, line, ',')) + { + ScoredSegmentPair scored_segment_pair; + scored_segment_pair.seed_pair.target_position_in_read = std::atoi(line.c_str()); + std::getline(scored_segment_pairs_file, line, ','); + scored_segment_pair.seed_pair.query_position_in_read = std::atoi(line.c_str()); + std::getline(scored_segment_pairs_file, line, ','); + scored_segment_pair.length = std::atoi(line.c_str()); + std::getline(scored_segment_pairs_file, line); + scored_segment_pair.score = std::atoi(line.c_str()); + scored_segment_pairs.push_back(scored_segment_pair); + } + } +} + +/// \brief Encodes character sequence as integer sequence +/// +/// \param[out] dst_seq Pointer to pre-allocated storage for encoded sequence +/// \param[in] src_seq Pointer to input sequence +/// \param[in] length Length of the sequence +inline void encode_sequence(int8_t* dst_seq, const char* src_seq, const int32_t length) +{ + for (int32_t i = 0; i < length; i++) + { + const char ch = src_seq[i]; + switch (ch) + { + case 'A': + dst_seq[i] = A_NT; + break; + case 'C': + dst_seq[i] = C_NT; + break; + case 'G': + dst_seq[i] = G_NT; + break; + case 'T': + dst_seq[i] = T_NT; + break; + case '&': + dst_seq[i] = E_NT; + break; + case 'n': + case 'N': + dst_seq[i] = N_NT; + break; + case 'a': + case 'c': + case 'g': + case 't': + dst_seq[i] = L_NT; + break; + default: + dst_seq[i] = X_NT; + break; + } + } +} + +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/samples/CMakeLists.txt b/cudaextender/samples/CMakeLists.txt new file mode 100644 index 000000000..43be7eadd --- /dev/null +++ b/cudaextender/samples/CMakeLists.txt @@ -0,0 +1,34 @@ +# +# Copyright 2020 NVIDIA CORPORATION. +# +# Licensed under the Apache License, Version 2.0 (the "License"); +# you may not use this file except in compliance with the License. +# You may obtain a copy of the License at +# +# http://www.apache.org/licenses/LICENSE-2.0 +# +# Unless required by applicable law or agreed to in writing, software +# distributed under the License is distributed on an "AS IS" BASIS, +# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +# See the License for the specific language governing permissions and +# limitations under the License. +# + + +set(MODULE_NAME sample_cudaextender) + +get_property(cudaextender_data_include_dir GLOBAL PROPERTY cudaextender_data_include_dir) +include_directories(${cudaextender_data_include_dir}) + +add_executable(${MODULE_NAME} + sample_cudaextender.cpp + ) + +target_link_libraries(${MODULE_NAME} + cudaextender + gwio + gwbase + ) + +install(TARGETS ${MODULE_NAME} + DESTINATION samples) diff --git a/cudaextender/samples/sample_cudaextender.cpp b/cudaextender/samples/sample_cudaextender.cpp new file mode 100644 index 000000000..53d4bd8e4 --- /dev/null +++ b/cudaextender/samples/sample_cudaextender.cpp @@ -0,0 +1,186 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +#include +#include +#include +#include +#include +#include +#include +#include + +#include +#include +#include +#include +#include + +using namespace claraparabricks::genomeworks; +using namespace cudautils; +using namespace cudaextender; + +static void print_scored_segment_pairs(const std::vector& scored_segment_pairs) +{ + std::cout << "Target Position, Query Position, Length, Score" << std::endl; + for (const auto& segment : scored_segment_pairs) + { + std::cout << segment.seed_pair.target_position_in_read << "," << segment.seed_pair.query_position_in_read + << "," << segment.length << "," << segment.score << std::endl; + } +} + +int main(int argc, char* argv[]) +{ + const int32_t xdrop_threshold = 910; + const bool input_no_entropy = false; + const int32_t score_threshold = 3000; + char c; + bool print = false; + bool help = false; + bool device_ptr_api_mode = false; + while ((c = getopt(argc, argv, "pdh")) != -1) + { + switch (c) + { + case 'p': + print = true; + break; + case 'd': + device_ptr_api_mode = true; + break; + case 'h': + default: + help = true; + break; + } + } + + if (help) + { + std::cout << "CUDAExtender API sample program. Runs ungapped extender on canned data." << std::endl; + std::cout << "-p : Print the Scored Segment Pair output to stdout." << std::endl; + std::cout << "-d : Use Device Pointer API. If not provided uses Host Pointer API." << std::endl; + std::cout << "-h : Print help message." << std::endl; + std::exit(0); + } + + // Fasta query and target files + const std::string target_file_path = std::string(CUDAEXTENDER_DATA_DIR) + "/sample.fa"; + std::unique_ptr fasta_parser_target = io::create_kseq_fasta_parser(target_file_path, 0, false); + // Assumes that only one sequence is present per file + const std::string target_sequence = fasta_parser_target->get_sequence_by_id(0).seq; + + const std::string query_file_path = std::string(CUDAEXTENDER_DATA_DIR) + "/sample.fa"; + std::unique_ptr fasta_parser_query = io::create_kseq_fasta_parser(query_file_path, 0, false); + // Assumes that only one sequence is present per file + const std::string query_sequence = fasta_parser_query->get_sequence_by_id(0).seq; + + // CSV SeedPairs file - Each row -> query_position_in_read_, + // target_position_in_read_ + const std::string seed_pairs_file_path = std::string(CUDAEXTENDER_DATA_DIR) + "/sample_seed_pairs.csv"; + + std::vector h_seed_pairs; + // Following function loops through all seed_pairs in the sample_seed_pairs.csv and returns + // results in the passed vector + parse_seed_pairs(seed_pairs_file_path, h_seed_pairs); + std::cerr << "Number of Seed Pairs: " << get_size(h_seed_pairs) << std::endl; + + // Define Scoring Matrix + const int32_t score_matrix[NUC2] = {91, -114, -31, -123, -1000, -1000, -100, -9100, + -114, 100, -125, -31, -1000, -1000, -100, -9100, + -31, -125, 100, -114, -1000, -1000, -100, -9100, + -123, -31, -114, 91, -1000, -1000, -100, -9100, + -1000, -1000, -1000, -1000, -1000, -1000, -1000, -9100, + -1000, -1000, -1000, -1000, -1000, -1000, -1000, -9100, + -100, -100, -100, -100, -1000, -1000, -100, -9100, + -9100, -9100, -9100, -9100, -9100, -9100, -9100, -9100}; + + // Allocate pinned memory for query and target strings + pinned_host_vector h_encoded_target(get_size(target_sequence)); + pinned_host_vector h_encoded_query(get_size(query_sequence)); + + encode_sequence(h_encoded_target.data(), target_sequence.c_str(), get_size(target_sequence)); + encode_sequence(h_encoded_query.data(), query_sequence.c_str(), get_size(query_sequence)); + // Create a stream for async use + CudaStream stream0 = make_cuda_stream(); + // Create an allocator for use with both APIs + const int64_t max_gpu_memory = cudautils::find_largest_contiguous_device_memory_section(); + DefaultDeviceAllocator allocator = create_default_device_allocator(max_gpu_memory); + // Reference for output + std::vector h_ssp; + // Create Ungapped Extender Object for both API modes + std::unique_ptr ungapped_extender = create_extender(score_matrix, + NUC2, + xdrop_threshold, + input_no_entropy, + stream0.get(), + 0, + allocator); + if (!device_ptr_api_mode) + { + ungapped_extender->extend_async(h_encoded_query.data(), + get_size(h_encoded_query), + h_encoded_target.data(), + get_size(h_encoded_target), + score_threshold, + h_seed_pairs); + ungapped_extender->sync(); + h_ssp = ungapped_extender->get_scored_segment_pairs(); + } + else + { + // Allocate space on device for target and query sequences, seed_pairs, + // scored segment pairs (ssp) and num_ssp using default allocator (caching) + // Allocate space for query and target sequences + device_buffer d_query(get_size(query_sequence), allocator, stream0.get()); + device_buffer d_target(get_size(target_sequence), allocator, stream0.get()); + // Allocate space for SeedPair input + device_buffer d_seed_pairs(get_size(h_seed_pairs), allocator, stream0.get()); + // Allocate space for ScoredSegmentPair output + device_buffer d_ssp(get_size(h_seed_pairs), allocator, stream0.get()); + device_buffer d_num_ssp(1, allocator, stream0.get()); + + // Async Memcopy all the input values to device + device_copy_n(h_encoded_query.data(), get_size(query_sequence), d_query.data(), stream0.get()); + device_copy_n(h_encoded_target.data(), get_size(target_sequence), d_target.data(), stream0.get()); + device_copy_n(h_seed_pairs.data(), get_size(h_seed_pairs), d_seed_pairs.data(), stream0.get()); + + // Launch the ungapped extender device pointer function + ungapped_extender->extend_async(d_query.data(), + get_size(d_query), + d_target.data(), + get_size(d_target), + score_threshold, + d_seed_pairs.data(), + get_size(d_seed_pairs), + d_ssp.data(), + d_num_ssp.data()); + + // Wait for ungapped extender to finish + GW_CU_CHECK_ERR(cudaStreamSynchronize(stream0.get())); + const int32_t h_num_ssp = cudautils::get_value_from_device(d_num_ssp.data(), stream0.get()); + h_ssp.resize(h_num_ssp); + // Copy data asynchronously + device_copy_n(d_ssp.data(), h_num_ssp, h_ssp.data(), stream0.get()); + cudaStreamSynchronize(stream0.get()); + } + std::cerr << "Number of Scored Segment Pairs found: " << get_size(h_ssp) << std::endl; + if (print) + { + print_scored_segment_pairs(h_ssp); + } + return 0; +} diff --git a/cudaextender/src/cudaextender.cpp b/cudaextender/src/cudaextender.cpp new file mode 100644 index 000000000..c345a4007 --- /dev/null +++ b/cudaextender/src/cudaextender.cpp @@ -0,0 +1,39 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +#include +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ + +StatusType Init() +{ + if (logging::LoggingStatus::success != logging::Init()) + return StatusType::generic_error; + + return StatusType::success; +} +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/src/extender.cpp b/cudaextender/src/extender.cpp new file mode 100644 index 000000000..6e37a037e --- /dev/null +++ b/cudaextender/src/extender.cpp @@ -0,0 +1,52 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +#include "ungapped_xdrop.cuh" + +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ + +std::unique_ptr create_extender(const int32_t* h_score_mat, + int32_t score_mat_dim, + int32_t xdrop_threshold, + bool no_entropy, + cudaStream_t stream, + int32_t device_id, + DefaultDeviceAllocator allocator, + ExtensionType type) +{ + if (type == ExtensionType::ungapped_xdrop) + { + return std::make_unique(h_score_mat, score_mat_dim, xdrop_threshold, no_entropy, stream, device_id, allocator); + } + else + { + throw std::runtime_error("Extender for specified type not implemented yet."); + } +} + +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/src/ungapped_xdrop.cu b/cudaextender/src/ungapped_xdrop.cu new file mode 100644 index 000000000..6aa2b438f --- /dev/null +++ b/cudaextender/src/ungapped_xdrop.cu @@ -0,0 +1,258 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +/* +* This algorithm was adapted from SegAlign's Ungapped Extender authored by +* Sneha Goenka (gsneha@stanford.edu) and Yatish Turakhia (yturakhi@uscs.edu). +* Source code for original implementation and use in SegAlign can be found +* here: https://github.com/gsneha26/SegAlign +*/ +#include "ungapped_xdrop.cuh" +#include "ungapped_xdrop_kernels.cuh" + +#include +#include + +#include +#include + +#include +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ + +using namespace cudautils; + +UngappedXDrop::UngappedXDrop(const int32_t* h_score_mat, const int32_t score_mat_dim, + const int32_t xdrop_threshold, const bool no_entropy, + cudaStream_t stream, const int32_t device_id, + DefaultDeviceAllocator allocator) + : h_score_mat_(h_score_mat, h_score_mat + score_mat_dim) + , score_mat_dim_(score_mat_dim) + , xdrop_threshold_(xdrop_threshold) + , no_entropy_(no_entropy) + , stream_(stream) + , device_id_(device_id) + , host_ptr_api_mode_(false) + , allocator_(allocator) +{ + // Switch to device for copying over initial structures + scoped_device_switch dev(device_id_); + + // Calculate the max limits on the number of extensions we can do on this GPU + cudaDeviceProp device_prop; + cudaGetDeviceProperties(&device_prop, device_id_); + + // TODO - Currently element and memory limits are artifacts of hardcoded global memory limits in + // SegAlign. To be replaced with actual calculation of memory requirements with sizes of + // datastructures taken into consideration. Also currently the max limit is based on total + // global memory, which should be replaced with memory available from the passed in allocator. + // Github Issue: https://github.com/clara-parabricks/GenomeWorks/issues/576 + const int32_t max_ungapped_per_gb = 4194304; + const float global_mem_gb = static_cast(device_prop.totalGlobalMem) / 1073741824.0f; + batch_max_ungapped_extensions_ = static_cast(global_mem_gb) * max_ungapped_per_gb; + + //Figure out memory requirements for cub functions + size_t temp_storage_bytes = 0; + size_t cub_storage_bytes = 0; + GW_CU_CHECK_ERR(cub::DeviceSelect::Unique(nullptr, + temp_storage_bytes, + d_tmp_ssp_.data(), + d_tmp_ssp_.data(), + (int32_t*)nullptr, + batch_max_ungapped_extensions_, + stream_)); + GW_CU_CHECK_ERR(cub::DeviceScan::InclusiveSum(nullptr, + cub_storage_bytes, + d_done_.data(), + d_done_.data(), + batch_max_ungapped_extensions_, + stream_)); + cub_storage_bytes = std::max(temp_storage_bytes, cub_storage_bytes); + + // Allocate space on device for scoring matrix and intermediate results + d_score_mat_ = device_buffer(score_mat_dim_, allocator_, stream_); + d_done_ = device_buffer(batch_max_ungapped_extensions_, allocator_, stream_); + d_tmp_ssp_ = device_buffer(batch_max_ungapped_extensions_, allocator_, stream_); + d_temp_storage_cub_ = device_buffer(cub_storage_bytes, allocator_, stream_); + device_copy_n(h_score_mat_.data(), score_mat_dim_, d_score_mat_.data(), stream_); +} + +StatusType UngappedXDrop::extend_async(const int8_t* d_query, const int32_t query_length, + const int8_t* d_target, const int32_t target_length, + const int32_t score_threshold, const SeedPair* d_seed_pairs, + const int32_t num_seed_pairs, ScoredSegmentPair* d_scored_segment_pairs, + int32_t* d_num_scored_segment_pairs) +{ + if (d_query == nullptr || d_target == nullptr || d_seed_pairs == nullptr) + { + GW_LOG_ERROR("Invalid input pointers"); + return StatusType::invalid_input; + } + if (d_scored_segment_pairs == nullptr || d_num_scored_segment_pairs == nullptr) + { + GW_LOG_ERROR("Invalid output pointers"); + return StatusType::invalid_input; + } + // Switch to configured GPU + scoped_device_switch dev(device_id_); + total_scored_segment_pairs_ = 0; + for (int32_t seed_pair_start = 0; seed_pair_start < num_seed_pairs; seed_pair_start += batch_max_ungapped_extensions_) + { + // TODO - Kernel optimizations [Unnecessary memset?] + // Github Issue: https://github.com/clara-parabricks/GenomeWorks/issues/579 + GW_CU_CHECK_ERR(cudaMemsetAsync((void*)d_done_.data(), 0, batch_max_ungapped_extensions_ * sizeof(int32_t), stream_)); + GW_CU_CHECK_ERR(cudaMemsetAsync((void*)d_tmp_ssp_.data(), 0, batch_max_ungapped_extensions_ * sizeof(ScoredSegmentPair), stream_)); + const int32_t curr_num_pairs = std::min(batch_max_ungapped_extensions_, num_seed_pairs - seed_pair_start); + find_high_scoring_segment_pairs<<<1024, 128, 0, stream_>>>(d_target, + target_length, + d_query, + query_length, + d_score_mat_.data(), + no_entropy_, + xdrop_threshold_, + score_threshold, + d_seed_pairs, + curr_num_pairs, + seed_pair_start, + d_scored_segment_pairs, + d_done_.data()); + size_t cub_storage_bytes = d_temp_storage_cub_.size(); + GW_CU_CHECK_ERR(cub::DeviceScan::InclusiveSum(d_temp_storage_cub_.data(), + cub_storage_bytes, + d_done_.data(), + d_done_.data(), + curr_num_pairs, + stream_)) + // TODO- Make output compression async. Currently synchronocity is arising due to + // thrust::stable_sort. Dynamic parallelism or an equivalent sort with cub can be used + // Github Issue: https://github.com/clara-parabricks/GenomeWorks/issues/578 + const int32_t num_scored_segment_pairs = get_value_from_device(d_done_.data() + curr_num_pairs - 1, stream_); + if (num_scored_segment_pairs > 0) + { + // TODO - Explore scaling up/down launch config based on workload. Also explore making + // this accessible to the user for configuration + // Github Issue: https://github.com/clara-parabricks/GenomeWorks/issues/577 + compress_output<<<1024, 1024, 0, stream_>>>(d_done_.data(), + seed_pair_start, + d_scored_segment_pairs, + d_tmp_ssp_.data(), + curr_num_pairs); + thrust::stable_sort(thrust::cuda::par(allocator_).on(stream_), + d_tmp_ssp_.begin(), + d_tmp_ssp_.begin() + num_scored_segment_pairs, + scored_segment_pair_comp()); + GW_CU_CHECK_ERR(cub::DeviceSelect::Unique(d_temp_storage_cub_.data(), + cub_storage_bytes, + d_tmp_ssp_.data(), + d_scored_segment_pairs + total_scored_segment_pairs_, + d_num_scored_segment_pairs, + num_scored_segment_pairs, + stream_)) + total_scored_segment_pairs_ += get_value_from_device(d_num_scored_segment_pairs, stream_); + } + } + + set_device_value_async(d_num_scored_segment_pairs, &total_scored_segment_pairs_, stream_); + + return StatusType::success; +} + +StatusType UngappedXDrop::extend_async(const int8_t* h_query, const int32_t query_length, + const int8_t* h_target, const int32_t target_length, + const int32_t score_threshold, + const std::vector& h_seed_pairs) +{ + // Reset the extender if it was used before in this mode + reset(); + // Set host pointer mode on + host_ptr_api_mode_ = true; + // Allocate space for query and target sequences + d_query_ = device_buffer(query_length, allocator_, stream_); + d_target_ = device_buffer(target_length, allocator_, stream_); + // Allocate space for SeedPair input + d_seed_pairs_ = device_buffer(h_seed_pairs.size(), allocator_, stream_); + // Allocate space for ScoredSegmentPair output + d_ssp_ = device_buffer(h_seed_pairs.size(), allocator_, stream_); + d_num_ssp_ = device_buffer(1, allocator_, stream_); + + // Async memcopy all the input values to device + device_copy_n(h_query, query_length, d_query_.data(), stream_); + device_copy_n(h_target, target_length, d_target_.data(), stream_); + device_copy_n(h_seed_pairs.data(), h_seed_pairs.size(), d_seed_pairs_.data(), stream_); + + // Launch the ungapped extender device function + return extend_async(d_query_.data(), query_length, + d_target_.data(), target_length, + score_threshold, d_seed_pairs_.data(), + d_seed_pairs_.size(), d_ssp_.data(), + d_num_ssp_.data()); +} + +StatusType UngappedXDrop::sync() +{ + if (host_ptr_api_mode_) + { + const int32_t h_num_ssp = get_value_from_device(d_num_ssp_.data(), stream_); + if (h_num_ssp > 0) + { + h_ssp_.resize(h_num_ssp); + device_copy_n(d_ssp_.data(), h_num_ssp, h_ssp_.data(), stream_); + GW_CU_CHECK_ERR(cudaStreamSynchronize(stream_)); + } + return StatusType::success; + } + + // If this function was called without using the host pointer API, throw error + return StatusType::invalid_operation; +} + +const std::vector& UngappedXDrop::get_scored_segment_pairs() const +{ + if (host_ptr_api_mode_) + { + return h_ssp_; + } + // If this function was called using the host pointer API, throw error + throw std::runtime_error("Invalid API call. Getting scored segment pairs without calling extend_async host ptr API"); +} + +void UngappedXDrop::reset() +{ + // Reset these only if host pointer API was used earlier + if (host_ptr_api_mode_) + { + h_ssp_.clear(); + host_ptr_api_mode_ = false; + } +} + +UngappedXDrop::~UngappedXDrop() +{ + UngappedXDrop::reset(); +} + +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/src/ungapped_xdrop.cuh b/cudaextender/src/ungapped_xdrop.cuh new file mode 100644 index 000000000..79684779d --- /dev/null +++ b/cudaextender/src/ungapped_xdrop.cuh @@ -0,0 +1,97 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +/* +* This algorithm was adapted from SegAlign's Ungapped Extender authored by +* Sneha Goenka (gsneha@stanford.edu) and Yatish Turakhia (yturakhi@uscs.edu). +* Source code for original implementation and use in SegAlign can be found +* here: https://github.com/gsneha26/SegAlign +*/ +#pragma once + +#include +#include +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ + +class UngappedXDrop : public Extender +{ +public: + UngappedXDrop(const int32_t* h_score_mat, + int32_t score_mat_dim, + int32_t xdrop_threshold, + bool no_entropy, + cudaStream_t stream, + int32_t device_id, + DefaultDeviceAllocator allocator); + ~UngappedXDrop() override; + + StatusType extend_async(const int8_t* h_query, int32_t query_length, + const int8_t* h_target, int32_t target_length, + int32_t score_threshold, + const std::vector& h_seed_pairs) override; + + StatusType extend_async(const int8_t* d_query, int32_t query_length, + const int8_t* d_target, int32_t target_length, + int32_t score_threshold, const SeedPair* d_seed_pairs, + int32_t num_seed_pairs, ScoredSegmentPair* d_scored_segment_pairs, + int32_t* d_num_scored_segment_pairs) override; + + StatusType sync() override; + + void reset() override; + + const std::vector& get_scored_segment_pairs() const override; + +private: + // Device ptr API required variables + DefaultDeviceAllocator allocator_; + pinned_host_vector h_score_mat_; + const int32_t score_mat_dim_; // Assume matrix is square + const int32_t xdrop_threshold_; + const bool no_entropy_; + cudaStream_t stream_; + const int32_t device_id_; + std::vector scored_segment_pairs_; + int32_t batch_max_ungapped_extensions_; + device_buffer d_score_mat_; // Pointer to device substitution matrix + device_buffer d_done_; + device_buffer d_tmp_ssp_; + int32_t total_scored_segment_pairs_; + device_buffer d_temp_storage_cub_; // temporary storage for cub functions + + // Host ptr API additional required variables + bool host_ptr_api_mode_; + device_buffer d_query_; + device_buffer d_target_; + device_buffer d_seed_pairs_; + device_buffer d_num_ssp_; + device_buffer d_ssp_; + std::vector h_ssp_; +}; + +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/src/ungapped_xdrop_kernels.cu b/cudaextender/src/ungapped_xdrop_kernels.cu new file mode 100644 index 000000000..bf0367e48 --- /dev/null +++ b/cudaextender/src/ungapped_xdrop_kernels.cu @@ -0,0 +1,481 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +/* +* This algorithm was adapted from SegAlign's Ungapped Extender authored by +* Sneha Goenka (gsneha@stanford.edu) and Yatish Turakhia (yturakhi@uscs.edu). +* Source code for original implementation and use in SegAlign can be found +* here: https://github.com/gsneha26/SegAlign +*/ +#include "ungapped_xdrop_kernels.cuh" + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ +// extend the seed values to a segment by ungapped x-drop method, adjust low-scoring +// segment scores based on entropy factor, compare resulting segment scores +// to score_threshold and update the d_scored_segment_pairs and d_done vectors +__global__ void find_high_scoring_segment_pairs(const int8_t* __restrict__ d_target, + const int32_t target_length, + const int8_t* __restrict__ d_query, + const int32_t query_length, + const int32_t* d_sub_mat, + const bool no_entropy, + const int32_t xdrop_threshold, + const int32_t score_threshold, + const SeedPair* d_seed_pairs, + const int32_t num_seed_pairs, + const int32_t start_index, + ScoredSegmentPair* d_scored_segment_pairs, + int32_t* d_done) +{ + // TODO - Kernel optimizations - + // Github Issue: https://github.com/clara-parabricks/GenomeWorks/issues/579 + + // TODO - Following variables are an artifact of the hardcoded encoding scheme with a fixed + // scoring matrix and a fixed alphabet. Will be replaced with cudasequence API. + // Github Issue: https://github.com/clara-parabricks/GenomeWorks/issues/574 + constexpr int32_t nuc = 8; + constexpr int32_t nuc2 = 64; + + constexpr int32_t num_warps = 4; + constexpr int32_t warp_size = 32; + const int32_t lane_id = threadIdx.x % warp_size; + const int32_t warp_id = (threadIdx.x - lane_id) / warp_size; + const float ln_4 = log(4.0f); + __shared__ int32_t ref_loc[num_warps]; + __shared__ int32_t query_loc[num_warps]; + __shared__ int32_t total_score[num_warps]; + __shared__ int32_t prev_score[num_warps]; + __shared__ int32_t prev_max_score[num_warps]; + __shared__ int32_t prev_max_pos[num_warps]; + __shared__ bool edge_found[num_warps]; + __shared__ bool xdrop_found[num_warps]; + __shared__ bool new_max_found[num_warps]; + __shared__ int32_t left_extent[num_warps]; + __shared__ int32_t extent[num_warps]; + __shared__ int32_t tile[num_warps]; + __shared__ int32_t sub_mat[nuc2]; + // TODO - Accuracy exploration required to check if the following member can be a float and to + // check the condition for entropy calculation. + // Github Issue: https://github.com/clara-parabricks/GenomeWorks/issues/575 + __shared__ double entropy[num_warps]; + + if (threadIdx.x < nuc2) + { + sub_mat[threadIdx.x] = d_sub_mat[threadIdx.x]; + } + __syncthreads(); + + for (int32_t hid0 = blockIdx.x * num_warps; hid0 < num_seed_pairs; hid0 += num_warps * gridDim.x) + { + short count[4] = {0}; + short count_del[4] = {0}; + const int32_t hid = hid0 + warp_id + start_index; + if (lane_id == 0) + { + if (hid < num_seed_pairs) + { + ref_loc[warp_id] = d_seed_pairs[hid].target_position_in_read; + query_loc[warp_id] = d_seed_pairs[hid].query_position_in_read; + } + else + { + ref_loc[warp_id] = d_seed_pairs[hid0].target_position_in_read; + query_loc[warp_id] = d_seed_pairs[hid0].query_position_in_read; + } + total_score[warp_id] = 0; + tile[warp_id] = 0; + xdrop_found[warp_id] = false; + edge_found[warp_id] = false; + new_max_found[warp_id] = false; + entropy[warp_id] = 1.0f; + prev_score[warp_id] = 0; + prev_max_score[warp_id] = -1000; + prev_max_pos[warp_id] = 0; + extent[warp_id] = 0; + } + __syncwarp(); + ////////////////////////////////////////////////////////////////// + //Right extension + while (!xdrop_found[warp_id] && !edge_found[warp_id]) + { + int32_t thread_score = 0; + const int32_t pos_offset = lane_id + tile[warp_id]; + const int32_t ref_pos = ref_loc[warp_id] + pos_offset; + const int32_t query_pos = query_loc[warp_id] + pos_offset; + int8_t r_chr; + int8_t q_chr; + + if (ref_pos < target_length && query_pos < query_length) + { + r_chr = d_target[ref_pos]; + q_chr = d_query[query_pos]; + thread_score = sub_mat[r_chr * nuc + q_chr]; + } + __syncwarp(); + +#pragma unroll + for (int32_t offset = 1; offset < warp_size; offset = offset << 1) + { + const int32_t temp = __shfl_up_sync(0xFFFFFFFF, thread_score, offset); + + if (lane_id >= offset) + { + thread_score += temp; + } + } + + thread_score += prev_score[warp_id]; + + int32_t max_pos; + int32_t max_thread_score; + + if (thread_score > prev_max_score[warp_id]) + { + max_thread_score = thread_score; + max_pos = pos_offset; + } + else + { + max_thread_score = prev_max_score[warp_id]; + max_pos = prev_max_pos[warp_id]; + } + + __syncwarp(); + +#pragma unroll + for (int32_t offset = 1; offset < warp_size; offset = offset << 1) + { + const int32_t temp = __shfl_up_sync(0xFFFFFFFF, max_thread_score, offset); + const int32_t temp_pos = __shfl_up_sync(0xFFFFFFFF, max_pos, offset); + + if (lane_id >= offset) + { + if (temp >= max_thread_score) + { + max_thread_score = temp; + max_pos = temp_pos; + } + } + } + + bool xdrop_done = ((max_thread_score - thread_score) > xdrop_threshold); + __syncwarp(); + +#pragma unroll + for (int32_t offset = 1; offset < warp_size; offset = offset << 1) + { + xdrop_done |= __shfl_up_sync(0xFFFFFFFF, xdrop_done, offset); + } + + if (lane_id == warp_size - 1) + { + new_max_found[warp_id] = max_pos > prev_max_pos[warp_id]; + prev_max_pos[warp_id] = max_pos; + if (xdrop_done) + { + total_score[warp_id] += max_thread_score; + xdrop_found[warp_id] = true; + extent[warp_id] = max_pos; + tile[warp_id] = max_pos; + } + else if (ref_pos >= target_length || query_pos >= query_length) + { + total_score[warp_id] += max_thread_score; + edge_found[warp_id] = true; + extent[warp_id] = max_pos; + tile[warp_id] = max_pos; + } + else + { + prev_score[warp_id] = thread_score; + prev_max_score[warp_id] = max_thread_score; + tile[warp_id] += warp_size; + } + } + __syncwarp(); + + if (new_max_found[warp_id]) + { +#pragma unroll + for (int32_t i = 0; i < 4; i++) + { + count[i] = count[i] + count_del[i]; + count_del[i] = 0; + } + } + __syncwarp(); + + if (r_chr == q_chr) + { + if (pos_offset <= prev_max_pos[warp_id]) + { + count[r_chr] += 1; + } + else + { + count_del[r_chr] += 1; + } + } + __syncwarp(); + } + + __syncwarp(); + + //////////////////////////////////////////////////////////////// + //Left extension + + if (lane_id == 0) + { + tile[warp_id] = 0; + xdrop_found[warp_id] = false; + edge_found[warp_id] = false; + new_max_found[warp_id] = false; + prev_score[warp_id] = 0; + prev_max_score[warp_id] = -1000; + prev_max_pos[warp_id] = 0; + left_extent[warp_id] = 0; + } + + count_del[0] = 0; + count_del[1] = 0; + count_del[2] = 0; + count_del[3] = 0; + __syncwarp(); + + while (!xdrop_found[warp_id] && !edge_found[warp_id]) + { + int32_t thread_score = 0; + const int32_t pos_offset = lane_id + 1 + tile[warp_id]; + int8_t r_chr; + int8_t q_chr; + + if (ref_loc[warp_id] >= pos_offset && query_loc[warp_id] >= pos_offset) + { + const int32_t ref_pos = ref_loc[warp_id] - pos_offset; + const int32_t query_pos = query_loc[warp_id] - pos_offset; + r_chr = d_target[ref_pos]; + q_chr = d_query[query_pos]; + thread_score = sub_mat[r_chr * nuc + q_chr]; + } + +#pragma unroll + for (int32_t offset = 1; offset < warp_size; offset = offset << 1) + { + const int32_t temp = __shfl_up_sync(0xFFFFFFFF, thread_score, offset); + + if (lane_id >= offset) + { + thread_score += temp; + } + } + + thread_score += prev_score[warp_id]; + + int32_t max_pos; + int32_t max_thread_score; + + if (thread_score > prev_max_score[warp_id]) + { + max_thread_score = thread_score; + max_pos = pos_offset; + } + else + { + max_thread_score = prev_max_score[warp_id]; + max_pos = prev_max_pos[warp_id]; + } + __syncwarp(); + +#pragma unroll + for (int32_t offset = 1; offset < warp_size; offset = offset << 1) + { + const int32_t temp = __shfl_up_sync(0xFFFFFFFF, max_thread_score, offset); + const int32_t temp_pos = __shfl_up_sync(0xFFFFFFFF, max_pos, offset); + + if (lane_id >= offset) + { + if (temp >= max_thread_score) + { + max_thread_score = temp; + max_pos = temp_pos; + } + } + } + + bool xdrop_done = ((max_thread_score - thread_score) > xdrop_threshold); + __syncwarp(); + +#pragma unroll + for (int32_t offset = 1; offset < warp_size; offset = offset << 1) + { + xdrop_done |= __shfl_up_sync(0xFFFFFFFF, xdrop_done, offset); + } + + if (lane_id == warp_size - 1) + { + new_max_found[warp_id] = max_pos > prev_max_pos[warp_id]; + prev_max_pos[warp_id] = max_pos; + if (xdrop_done) + { + total_score[warp_id] += max_thread_score; + xdrop_found[warp_id] = true; + left_extent[warp_id] = max_pos; + extent[warp_id] += left_extent[warp_id]; + tile[warp_id] = max_pos; + } + else if (ref_loc[warp_id] < pos_offset || query_loc[warp_id] < pos_offset) + { + total_score[warp_id] += max_thread_score; + edge_found[warp_id] = true; + left_extent[warp_id] = max_pos; + extent[warp_id] += left_extent[warp_id]; + tile[warp_id] = max_pos; + } + else + { + prev_score[warp_id] = thread_score; + prev_max_score[warp_id] = max_thread_score; + tile[warp_id] += warp_size; + } + } + __syncwarp(); + + if (new_max_found[warp_id]) + { +#pragma unroll + for (int32_t i = 0; i < 4; i++) + { + count[i] = count[i] + count_del[i]; + count_del[i] = 0; + } + } + __syncwarp(); + + if (r_chr == q_chr) + { + if (pos_offset <= prev_max_pos[warp_id]) + { + count[r_chr] += 1; + } + else + { + count_del[r_chr] += 1; + } + } + __syncwarp(); + } + + ////////////////////////////////////////////////////////////////// + + if (total_score[warp_id] >= score_threshold && total_score[warp_id] <= 3 * score_threshold && !no_entropy) + { + for (int32_t i = 0; i < 4; i++) + { +#pragma unroll + for (int32_t offset = 1; offset < warp_size; offset = offset << 1) + { + count[i] += __shfl_up_sync(0xFFFFFFFF, count[i], offset); + } + } + __syncwarp(); + + if (lane_id == warp_size - 1 && ((count[0] + count[1] + count[2] + count[3]) >= 20)) + { + double entropy_ln = 0.f; +#pragma unroll + for (int32_t i = 0; i < 4; i++) + { + if (count[i] != 0) + { + const double probability = static_cast(count[i]) / static_cast(extent[warp_id] + 1); + entropy_ln += (probability)*log(probability); + } + } + entropy[warp_id] = -entropy_ln / ln_4; // Store Entropy with log base 4 + } + } + __syncwarp(); + + ////////////////////////////////////////////////////////////////// + + if (hid < num_seed_pairs) + { + if (lane_id == 0) + { + if (static_cast(static_cast(total_score[warp_id]) * entropy[warp_id]) >= score_threshold) + { + d_scored_segment_pairs[hid].seed_pair.target_position_in_read = ref_loc[warp_id] - left_extent[warp_id]; + d_scored_segment_pairs[hid].seed_pair.query_position_in_read = query_loc[warp_id] - left_extent[warp_id]; + d_scored_segment_pairs[hid].length = extent[warp_id]; + if (entropy[warp_id] > 0) + d_scored_segment_pairs[hid].score = total_score[warp_id] * entropy[warp_id]; + d_done[hid - start_index] = 1; + } + else + { + d_scored_segment_pairs[hid].seed_pair.target_position_in_read = ref_loc[warp_id]; + d_scored_segment_pairs[hid].seed_pair.query_position_in_read = query_loc[warp_id]; + d_scored_segment_pairs[hid].length = 0; + d_scored_segment_pairs[hid].score = 0; + d_done[hid - start_index] = 0; + } + } + } + __syncwarp(); + } +} + +// Gather the SSPs from the resulting segments to the beginning of the tmp_ssp array +__global__ void compress_output(const int32_t* d_done, + const int32_t start_index, + const ScoredSegmentPair* d_ssp, + ScoredSegmentPair* d_tmp_ssp, + const int32_t num_seed_pairs) +{ + const int32_t stride = blockDim.x * gridDim.x; + const int32_t start = blockDim.x * blockIdx.x + threadIdx.x; + for (int32_t id = start; id < num_seed_pairs; id += stride) + { + const int32_t reduced_index = d_done[id]; + const int32_t index = id + start_index; + if (index > 0) + { + if (reduced_index > d_done[index - 1]) + { + d_tmp_ssp[reduced_index - 1] = d_ssp[index]; + } + } + else + { + if (reduced_index == 1) + { + d_tmp_ssp[0] = d_ssp[start_index]; + } + } + } +} + +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/src/ungapped_xdrop_kernels.cuh b/cudaextender/src/ungapped_xdrop_kernels.cuh new file mode 100644 index 000000000..befd9bea0 --- /dev/null +++ b/cudaextender/src/ungapped_xdrop_kernels.cuh @@ -0,0 +1,99 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +/* +* This algorithm was adapted from SegAlign's Ungapped Extender authored by +* Sneha Goenka (gsneha@stanford.edu) and Yatish Turakhia (yturakhi@uscs.edu). +* Source code for original implementation and use in SegAlign can be found +* here: https://github.com/gsneha26/SegAlign +*/ +#pragma once + +#include "ungapped_xdrop.cuh" + +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ + +// extend the hits to a segment by ungapped x-drop method, adjust low-scoring +// segment scores based on entropy factor, compare resulting segment scores +// to score_threshold and update the d_scored_segment_pairs and d_done vectors +__global__ void find_high_scoring_segment_pairs(const int8_t* __restrict__ d_target, + const int32_t target_length, + const int8_t* __restrict__ d_query, + const int32_t query_length, + const int32_t* d_sub_mat, + const bool no_entropy, + const int32_t xdrop_threshold, + const int32_t score_threshold, + const SeedPair* __restrict__ d_seed_pairs, + const int32_t num_seed_pairs, + const int32_t start_index, + ScoredSegmentPair* d_scored_segment_pairs, + int32_t* d_done); + +// Gathers the SSPs from the resulting segments to the beginning of the +// tmp_ssp vector +__global__ void compress_output(const int32_t* d_done, + const int32_t start_index, + const ScoredSegmentPair* d_ssp, + ScoredSegmentPair* d_tmp_ssp, + int num_hits); + +// Binary predicate for sorting the ScoredSegmentPairs +struct scored_segment_pair_comp +{ + __host__ __device__ bool operator()(const ScoredSegmentPair& x, const ScoredSegmentPair& y) + { + if (x.seed_pair.query_position_in_read < y.seed_pair.query_position_in_read) + return true; + else if (x.seed_pair.query_position_in_read == y.seed_pair.query_position_in_read) + { + if (x.length > y.length) + return true; + else if (x.length == y.length) + { + if (x.seed_pair.target_position_in_read < y.seed_pair.target_position_in_read) + return true; + else if (x.seed_pair.target_position_in_read == y.seed_pair.target_position_in_read) + { + if (x.score > y.score) + return true; + else + return false; + } + else + return false; + } + else + return false; + } + else + return false; + } +}; + +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/tests/CMakeLists.txt b/cudaextender/tests/CMakeLists.txt new file mode 100644 index 000000000..7c774c8cc --- /dev/null +++ b/cudaextender/tests/CMakeLists.txt @@ -0,0 +1,29 @@ +# +# Copyright 2020 NVIDIA CORPORATION. +# +# Licensed under the Apache License, Version 2.0 (the "License"); +# you may not use this file except in compliance with the License. +# You may obtain a copy of the License at +# +# http://www.apache.org/licenses/LICENSE-2.0 +# +# Unless required by applicable law or agreed to in writing, software +# distributed under the License is distributed on an "AS IS" BASIS, +# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +# See the License for the specific language governing permissions and +# limitations under the License. +# + + +set(TARGET_NAME cudaextendertests) + +set(SOURCES + main.cpp + Test_CudaextenderEnd2End.cu) + +get_property(cudextender_data_include_dir GLOBAL PROPERTY cudaextender_data_include_dir) +include_directories(${cudextender_data_include_dir}) + +set(LIBS cudaextender) + +gw_add_tests(${TARGET_NAME} "${SOURCES}" "${LIBS}") diff --git a/cudaextender/tests/Test_CudaextenderEnd2End.cu b/cudaextender/tests/Test_CudaextenderEnd2End.cu new file mode 100644 index 000000000..c818d77d6 --- /dev/null +++ b/cudaextender/tests/Test_CudaextenderEnd2End.cu @@ -0,0 +1,127 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ +#include "gtest/gtest.h" + +#include +#include +#include +#include +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudaextender +{ + +struct End2EndTestParam +{ + std::string query_file; + std::string target_file; + std::string seed_pairs_file; + std::string golden_scored_segment_pairs_file; + int32_t score_threshold; +}; + +std::vector getCudaextenderEnd2EndTestCases() +{ + std::vector test_cases; + + End2EndTestParam test1{}; + test1.query_file = std::string(CUDAEXTENDER_DATA_DIR) + "/sample.fa"; + test1.target_file = std::string(CUDAEXTENDER_DATA_DIR) + "/sample.fa"; + test1.seed_pairs_file = std::string(CUDAEXTENDER_DATA_DIR) + "/sample_seed_pairs.csv"; + test1.golden_scored_segment_pairs_file = std::string(CUDAEXTENDER_DATA_DIR) + "/sample_scored_segment_pairs.csv"; + test1.score_threshold = 3000; + test_cases.push_back(test1); + + return test_cases; +} + +// Testing correctness of UngappedXDrop extension End2End with default scoring matrix +class TestCudaextenderEnd2End : public ::testing::TestWithParam +{ +public: + void SetUp() + { + param_ = GetParam(); + // Define Scoring Matrix + int32_t score_matrix[NUC2] = {91, -114, -31, -123, -1000, -1000, -100, -9100, + -114, 100, -125, -31, -1000, -1000, -100, -9100, + -31, -125, 100, -114, -1000, -1000, -100, -9100, + -123, -31, -114, 91, -1000, -1000, -100, -9100, + -1000, -1000, -1000, -1000, -1000, -1000, -1000, -9100, + -1000, -1000, -1000, -1000, -1000, -1000, -1000, -9100, + -100, -100, -100, -100, -1000, -1000, -100, -9100, + -9100, -9100, -9100, -9100, -9100, -9100, -9100, -9100}; + const int32_t xdrop_threshold = 910; + const int32_t device_id = 0; + const bool no_entropy = false; + const std::size_t max_gpu_memory = cudautils::find_largest_contiguous_device_memory_section(); + allocator_ = create_default_device_allocator(max_gpu_memory); + stream_ = make_cuda_stream(); + ungapped_extender_ = create_extender(score_matrix, NUC2, xdrop_threshold, no_entropy, stream_.get(), device_id, allocator_); + } + + void TearDown() + { + ungapped_extender_.reset(); + } + +protected: + std::unique_ptr ungapped_extender_; + End2EndTestParam param_; + CudaStream stream_; + DefaultDeviceAllocator allocator_; +}; + +TEST_P(TestCudaextenderEnd2End, TestCorrectness) +{ + std::unique_ptr fasta_parser_target = io::create_kseq_fasta_parser(param_.target_file, 0, false); + const std::string target_sequence = fasta_parser_target->get_sequence_by_id(0).seq; + std::unique_ptr fasta_parser_query = io::create_kseq_fasta_parser(param_.query_file, 0, false); + const std::string query_sequence = fasta_parser_query->get_sequence_by_id(0).seq; + std::vector h_seed_pairs; + parse_seed_pairs(param_.seed_pairs_file, h_seed_pairs); + // Allocate pinned memory for query and target strings + pinned_host_vector h_encoded_target(target_sequence.length()); + pinned_host_vector h_encoded_query(target_sequence.length()); + encode_sequence(h_encoded_target.data(), target_sequence.c_str(), target_sequence.length()); + encode_sequence(h_encoded_query.data(), query_sequence.c_str(), query_sequence.length()); + ungapped_extender_->extend_async(h_encoded_query.data(), + get_size(h_encoded_query), + h_encoded_target.data(), + get_size(h_encoded_target), + param_.score_threshold, + h_seed_pairs); + // Parse golden scored_segment_pairs while extension is in progress + std::vector golden_scored_segment_pairs; + parse_scored_segment_pairs(param_.golden_scored_segment_pairs_file, golden_scored_segment_pairs); + ungapped_extender_->sync(); + std::vector scored_segment_pairs = ungapped_extender_->get_scored_segment_pairs(); + ASSERT_EQ(golden_scored_segment_pairs, scored_segment_pairs); +} + +INSTANTIATE_TEST_SUITE_P(TestEnd2End, TestCudaextenderEnd2End, ::testing::ValuesIn(getCudaextenderEnd2EndTestCases())); + +} // namespace cudaextender + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudaextender/tests/main.cpp b/cudaextender/tests/main.cpp new file mode 100644 index 000000000..f8017e551 --- /dev/null +++ b/cudaextender/tests/main.cpp @@ -0,0 +1,25 @@ +/* +* Copyright 2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ + +#include "gtest/gtest.h" + +// ----------------------------------------------------------------------------- +int main(int argc, char** argv) +{ + ::testing::InitGoogleTest(&argc, argv); + + return RUN_ALL_TESTS(); +} diff --git a/cudamapper/CMakeLists.txt b/cudamapper/CMakeLists.txt index d50bd6bf1..22868ecd3 100644 --- a/cudamapper/CMakeLists.txt +++ b/cudamapper/CMakeLists.txt @@ -67,10 +67,23 @@ target_include_directories(${MODULE_NAME} $ $ ) -target_link_libraries(${MODULE_NAME} gwbase gwio cub) -target_compile_options(${MODULE_NAME} PRIVATE -Werror) + +# optionally link against htslib +if (TARGET htslib_project) + target_compile_definitions(${MODULE_NAME} PUBLIC GW_BUILD_HTSLIB) + add_dependencies(${MODULE_NAME} htslib_project) + target_link_libraries(${MODULE_NAME} htslib gwbase gwio cub) +else() + target_link_libraries(${MODULE_NAME} gwbase gwio cub) +endif() + +target_compile_options(${MODULE_NAME} PRIVATE -Werror -Wall -Wextra) +if (gw_optimize_for_native_cpu) + target_compile_options(${MODULE_NAME} PRIVATE -march=native) +endif() add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/include) +add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/README.md) cuda_add_executable(${MODULE_NAME}-bin src/main.cu @@ -79,6 +92,9 @@ cuda_add_executable(${MODULE_NAME}-bin target_compile_options(${MODULE_NAME}-bin PRIVATE -Werror) target_link_libraries(${MODULE_NAME}-bin ${MODULE_NAME} cudaaligner) set_target_properties(${MODULE_NAME}-bin PROPERTIES OUTPUT_NAME ${MODULE_NAME}) +if (TARGET htslib_project) + target_compile_definitions(${MODULE_NAME}-bin PUBLIC GW_BUILD_HTSLIB) +endif() # Add tests folder diff --git a/cudamapper/README.md b/cudamapper/README.md new file mode 100644 index 000000000..85fe8be9c --- /dev/null +++ b/cudamapper/README.md @@ -0,0 +1,31 @@ +# cudamapper + +The `cudamapper` package provides minimizer-based GPU-accelerated approximate mapping. + +## Library +Built as `libcudamapper.[so|a]` + +* `Indexer` module to generate an index of minimizers from a list of sequences. +* `Matcher` module to find locations of matching pairs of minimizers between sequences using minimizer indices. +* `Overlapper` module to generate overlaps from sequence of minimizer matches generated by matcher. + +APIs documented in [include](include/claraparabricks/genomeworks/cudamapper) folder. + +## Sample +[sample_cudamapper](samples/sample_cudamapper.cpp) - A prototypical binary highlighting the usage of `libcudamapper` APIs (indexer, matcher and overlapper) and +techniques to tie them into an application. + +## Tool + +`cudamapper` is an end-to-end command line to for sequence to sequence mapping. `cudamapper` outputs +mappings in the PAF format and is currently optimised for all-vs-all long read (ONT, Pacific Biosciences) sequences. + +To run all-vs all overlaps use the following command: + +`cudamapper in.fasta in.fasta` + +A query fasta can be mapped to a reference as follows: + +`cudamapper query.fasta target.fasta` + +To access more information about running cudamapper, run `cudamapper --help`. diff --git a/cudamapper/include/claraparabricks/genomeworks/cudamapper/index.hpp b/cudamapper/include/claraparabricks/genomeworks/cudamapper/index.hpp index 001cbc829..abb142e20 100644 --- a/cudamapper/include/claraparabricks/genomeworks/cudamapper/index.hpp +++ b/cudamapper/include/claraparabricks/genomeworks/cudamapper/index.hpp @@ -16,9 +16,9 @@ #pragma once +#include #include #include -#include #include #include #include @@ -35,6 +35,51 @@ namespace cudamapper /// \addtogroup cudamapper /// \{ +/// IndexDescriptor Implementation - Every Index is defined by its first read and the number of reads +/// Used in conjunction with a fasta parser object to create an index +class IndexDescriptor +{ +public: + /// \brief constructor + IndexDescriptor(read_id_t first_read, + number_of_reads_t number_of_reads); + + /// \brief getter + read_id_t first_read() const; + + /// \brief getter + number_of_reads_t number_of_reads() const; + + /// \brief returns hash value + std::size_t get_hash() const; + +private: + /// \brief generates hash + void generate_hash(); + + /// first read in index + read_id_t first_read_; + /// number of reads in index + number_of_reads_t number_of_reads_; + /// hash of this object + std::size_t hash_; +}; + +/// \brief equality operator +bool operator==(const IndexDescriptor& lhs, + const IndexDescriptor& rhs); + +/// \brief inequality operator +bool operator!=(const IndexDescriptor& lhs, + const IndexDescriptor& rhs); + +/// IndexDescriptorHash - operator() calculates hash of a given IndexDescriptor +struct IndexDescriptorHash +{ + /// \brief caclulates hash of given IndexDescriptor + std::size_t operator()(const IndexDescriptor& index_descriptor) const; +}; + /// Index - manages mapping of (k,w)-kmer-representation and all its occurences class Index { @@ -43,73 +88,92 @@ class Index virtual ~Index() = default; /// \brief returns an array of representations of sketch elements + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of representations of sketch elements virtual const device_buffer& representations() const = 0; /// \brief returns an array of reads ids for sketch elements + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of reads ids for sketch elements virtual const device_buffer& read_ids() const = 0; /// \brief returns an array of starting positions of sketch elements in their reads + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of starting positions of sketch elements in their reads virtual const device_buffer& positions_in_reads() const = 0; /// \brief returns an array of directions in which sketch elements were read + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of directions in which sketch elements were read virtual const device_buffer& directions_of_reads() const = 0; /// \brief returns an array where each representation is recorder only once, sorted by representation + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array where each representation is recorder only once, sorted by representation virtual const device_buffer& unique_representations() const = 0; /// \brief returns first occurrence of corresponding representation from unique_representations() in data arrays + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return first occurrence of corresponding representation from unique_representations() in data arrays virtual const device_buffer& first_occurrence_of_representations() const = 0; /// \brief returns number of reads in input data + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return number of reads in input data virtual read_id_t number_of_reads() const = 0; /// \brief returns smallest read_id in index + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return smallest read_id in index (0 if empty index) virtual read_id_t smallest_read_id() const = 0; /// \brief returns largest read_id in index + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return largest read_id in index (0 if empty index) virtual read_id_t largest_read_id() const = 0; /// \brief returns length of the longest read in this index + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return length of the longest read in this index virtual position_in_read_t number_of_basepairs_in_longest_read() const = 0; /// \brief Return the maximum kmer length allowable + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return Return the maximum kmer length allowable static uint64_t maximum_kmer_size() { return sizeof(representation_t) * CHAR_BIT / 2; } + /// \brief checks if index is ready to be used on this device, index might not be ready if its creation or copy from host is asynchronous + /// \return true if the index is ready to be used + virtual bool is_ready() const = 0; + + /// \brief if is_ready() is true returns immediately, blocks until it becomes ready otherwise + virtual void wait_to_be_ready() = 0; + /// \brief generates a mapping of (k,w)-kmer-representation to all of its occurrences for one or more sequences + /// Generation is done asynchronously and one should call wait_to_be_ready() before using the object /// \param allocator The device memory allocator to use for temporary buffer allocations /// \param parser parser for the whole input file (part that goes into this index is determined by first_read_id and past_the_last_read_id) - /// \param first_read_id read_id of the first read to the included in this index - /// \param past_the_last_read_id read_id+1 of the last read to be included in this index + /// \param descriptor object holding the first read, size of the read, and hash value of the index being created /// \param kmer_size k - the kmer length /// \param window_size w - the length of the sliding window used to find sketch elements (i.e. the number of adjacent kmers in a window, adjacent = shifted by one basepair) /// \param hash_representations if true, hash kmer representations /// \param filtering_parameter filter out all representations for which number_of_sketch_elements_with_that_representation/total_skech_elements >= filtering_parameter, filtering_parameter == 1.0 disables filtering - /// \param cuda_stream CUDA stream on which the work is to be done. Device arrays are also associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor is done + /// \param cuda_stream_generation CUDA stream on which index is generated. Device arrays are associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor has been done + /// \param cuda_stream_copy CUDA stream on which the index is copied to host if needed. Device arrays are associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor has been done /// \return instance of Index static std::unique_ptr - create_index(DefaultDeviceAllocator allocator, - const io::FastaParser& parser, - const read_id_t first_read_id, - const read_id_t past_the_last_read_id, - const std::uint64_t kmer_size, - const std::uint64_t window_size, - const bool hash_representations = true, - const double filtering_parameter = 1.0, - const cudaStream_t cuda_stream = 0); + create_index_async(DefaultDeviceAllocator allocator, + const io::FastaParser& parser, + const IndexDescriptor& descriptor, + const std::uint64_t kmer_size, + const std::uint64_t window_size, + const bool hash_representations = true, + const double filtering_parameter = 1.0, + const cudaStream_t cuda_stream_generation = 0, + const cudaStream_t cuda_stream_copy = 0); }; /// IndexHostCopyBase - Creates and maintains a copy of computed IndexGPU elements on the host, then allows to retrieve target @@ -118,6 +182,17 @@ class Index class IndexHostCopyBase { public: + /// Span - helper struct that provides a view of part of underlying array + /// \tparam T type of data in this view + template + struct Span + { + /// pointer to first element in view + T* data; + /// total elements of type T in view + std::ptrdiff_t size; + }; + /// \brief copy cached index vectors from the host and create an object of Index on GPU /// \param allocator asynchronous device allocator used for temporary buffer allocations /// \param cuda_stream H2D copy is done on this stream. Device arrays are also associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor is done @@ -128,29 +203,32 @@ class IndexHostCopyBase /// \brief virtual destructor virtual ~IndexHostCopyBase() = default; + /// \brief waits for copy to host to be done + virtual void finish_copying() const = 0; + /// \brief returns an array of representations of sketch elements (stored on host) /// \return an array of representations of sketch elements - virtual const std::vector& representations() const = 0; + virtual const Span representations() const = 0; /// \brief returns an array of reads ids for sketch elements (stored on host) /// \return an array of reads ids for sketch elements - virtual const std::vector& read_ids() const = 0; + virtual const Span read_ids() const = 0; /// \brief returns an array of starting positions of sketch elements in their reads (stored on host) /// \return an array of starting positions of sketch elements in their reads - virtual const std::vector& positions_in_reads() const = 0; + virtual const Span positions_in_reads() const = 0; /// \brief returns an array of directions in which sketch elements were read (stored on host) /// \return an array of directions in which sketch elements were read - virtual const std::vector& directions_of_reads() const = 0; + virtual const Span directions_of_reads() const = 0; /// \brief returns an array where each representation is recorded only once, sorted by representation (stored on host) /// \return an array where each representation is recorded only once, sorted by representation - virtual const std::vector& unique_representations() const = 0; + virtual const Span unique_representations() const = 0; /// \brief returns first occurrence of corresponding representation from unique_representations(), plus one more element with the total number of sketch elements (stored on host) /// \return first occurrence of corresponding representation from unique_representations(), plus one more element with the total number of sketch elements - virtual const std::vector& first_occurrence_of_representations() const = 0; + virtual const Span first_occurrence_of_representations() const = 0; /// \brief returns number of reads in input data /// \return number of reads in input data @@ -172,64 +250,34 @@ class IndexHostCopyBase /// \return window_size_ virtual std::uint64_t window_size() const = 0; - /// \brief Constructor - /// \brief creates a copy of input processed index on the host + /// \brief Starts creating a copy of index on the host + /// Copy is done asynchronously and one should wait for it to finish with finish_copying() /// \param index - pointer to computed index parameters (vectors of sketch elements) on GPU /// \param first_read_id - representing smallest read_id in index /// \param kmer_size - number of basepairs in a k-mer /// \param window_size the number of adjacent k-mers in a window, adjacent = shifted by one basepair /// \param cuda_stream D2H copy is done on this stream /// \return - an instance of IndexHostCopyBase - static std::unique_ptr create_cache(const Index& index, - const read_id_t first_read_id, - const std::uint64_t kmer_size, - const std::uint64_t window_size, - const cudaStream_t cuda_stream = 0); + static std::unique_ptr create_host_copy_async(const Index& index, + const read_id_t first_read_id, + const std::uint64_t kmer_size, + const std::uint64_t window_size, + const cudaStream_t cuda_stream = 0); }; -/// IndexDescriptor Implementation - Every Index is defined by its first read and the number of reads -/// Used in conjunction with a fasta parser object to create an index -class IndexDescriptor +/// IndexNotReadyException - Exception to be thrown if a member of Index is accessed, but is_read() == false +class IndexNotReadyException : public std::exception { public: - /// \brief constructor - IndexDescriptor(read_id_t first_read, - number_of_reads_t number_of_reads); - - /// \brief getter - read_id_t first_read() const; - - /// \brief getter - number_of_reads_t number_of_reads() const; + /// \brief Constructor + /// \param function_name name of funciton which has been accessed + IndexNotReadyException(const std::string& function_name); - /// \brief returns hash value - std::size_t get_hash() const; + /// \brief Returns the error message of the exception + const char* what() const noexcept override; private: - /// \brief generates hash - void generate_hash(); - - /// first read in index - read_id_t first_read_; - /// number of reads in index - number_of_reads_t number_of_reads_; - /// hash of this object - std::size_t hash_; -}; - -/// \brief equality operator -bool operator==(const IndexDescriptor& lhs, - const IndexDescriptor& rhs); - -/// \brief inequality operator -bool operator!=(const IndexDescriptor& lhs, - const IndexDescriptor& rhs); - -/// IndexDescriptorHash - operator() calculates hash of a given IndexDescriptor -struct IndexDescriptorHash -{ - /// \brief caclulates hash of given IndexDescriptor - std::size_t operator()(const IndexDescriptor& index_descriptor) const; + const std::string message_; }; } // namespace cudamapper diff --git a/cudamapper/include/claraparabricks/genomeworks/cudamapper/utils.hpp b/cudamapper/include/claraparabricks/genomeworks/cudamapper/utils.hpp index bc6a7bd61..227bf097c 100644 --- a/cudamapper/include/claraparabricks/genomeworks/cudamapper/utils.hpp +++ b/cudamapper/include/claraparabricks/genomeworks/cudamapper/utils.hpp @@ -20,6 +20,10 @@ #include #include +#ifdef GW_BUILD_HTSLIB +#include "sam.h" +#endif + #include #include @@ -37,6 +41,14 @@ class FastaParser; namespace cudamapper { +// enum to determine output format +enum class OutputFormat +{ + PAF, + SAM, + BAM +}; + /// \brief prints overlaps to stdout in PAF format /// \param overlaps vector of overlap objects /// \param cigars CIGAR strings. Empty vector if none exist @@ -51,6 +63,25 @@ void print_paf(const std::vector& overlaps, int32_t kmer_size, std::mutex& write_output_mutex); +#ifdef GW_BUILD_HTSLIB +/// \brief prints overlaps to stdout in BAM format +/// \param overlaps vector of overlap objects +/// \param cigars CIGAR strings. Empty vector if none exist +/// \param query_parser needed for read names and lengths +/// \param target_parser needed for read names and lengths +/// \param format print in either BAM or SAM +/// \param write_output_mutex mutex that enables exclusive access to output stream +/// \param argc (optional) number of command line arguments used to generated the @PG CL sections +/// \param argv (optional) command line arguments used to generated the @PG CL sections +void print_sam(const std::vector& overlaps, + const std::vector& cigars, + const io::FastaParser& query_parser, + const io::FastaParser& target_parser, + OutputFormat format, + std::mutex& write_output_mutex, + int argc = -1, + char* argv[] = nullptr); +#endif /// \brief returns a vector of IndexDescriptors in which the sum of basepairs of all reads in one IndexDescriptor is at most max_basepairs_per_index /// If a single read exceeds max_chunk_size it will be placed in its own IndexDescriptor. /// @@ -59,6 +90,7 @@ void print_paf(const std::vector& overlaps, /// \return vector of IndexDescriptors std::vector group_reads_into_indices(const io::FastaParser& parser, number_of_basepairs_t max_basepairs_per_index = 1000000); + } // namespace cudamapper } // namespace genomeworks diff --git a/cudamapper/samples/CMakeLists.txt b/cudamapper/samples/CMakeLists.txt index 503cbfb28..ca0684314 100644 --- a/cudamapper/samples/CMakeLists.txt +++ b/cudamapper/samples/CMakeLists.txt @@ -27,5 +27,11 @@ target_link_libraries(${MODULE_NAME} cudamapper ) +if (TARGET htslib_project) + target_compile_definitions(${MODULE_NAME} + PUBLIC + GW_BUILD_HTSLIB) +endif() + install(TARGETS ${MODULE_NAME} DESTINATION samples) diff --git a/cudamapper/samples/sample_cudamapper.cpp b/cudamapper/samples/sample_cudamapper.cpp index c35ebe766..142439d4b 100644 --- a/cudamapper/samples/sample_cudamapper.cpp +++ b/cudamapper/samples/sample_cudamapper.cpp @@ -29,6 +29,7 @@ #include #include #include +#include // define constants. See cudamapper/src/application_parameters.hpp for more. // constants used in multiple places @@ -73,7 +74,8 @@ void process_batch(std::vector& query_index_descriptors, const std::shared_ptr query_parser, const std::shared_ptr target_parser, DefaultDeviceAllocator allocator, - bool print) + const bool print, + const OutputFormat format) { // extra variables used in print_paf. Note "cigars" are typically found during alignment. const std::vector cigars(0); @@ -82,28 +84,28 @@ void process_batch(std::vector& query_index_descriptors, // process the pairs of query and target indices for (const IndexDescriptor& query_index_descriptor : query_index_descriptors) { - std::unique_ptr query_index = Index::create_index(allocator, - *query_parser, - query_index_descriptor.first_read(), - query_index_descriptor.first_read() + query_index_descriptor.number_of_reads(), - KMER_SIZE, - WINDOWS_SIZE, - true, // hash representations - FILTERING_PARAMETER); // filter parameter + std::unique_ptr query_index = Index::create_index_async(allocator, + *query_parser, + query_index_descriptor, + KMER_SIZE, + WINDOWS_SIZE, + true, // hash representations + FILTERING_PARAMETER); // filter parameter + query_index->wait_to_be_ready(); for (const IndexDescriptor& target_index_descriptor : target_index_descriptors) { // skip pairs in which target batch has smaller id than query batch as it will be covered by symmetry if (target_index_descriptor.first_read() >= query_index_descriptor.first_read()) { - std::unique_ptr target_index = Index::create_index(allocator, - *target_parser, - target_index_descriptor.first_read(), - target_index_descriptor.first_read() + target_index_descriptor.number_of_reads(), - KMER_SIZE, - WINDOWS_SIZE, - true, // hash representations - FILTERING_PARAMETER); // filter parameter + std::unique_ptr target_index = Index::create_index_async(allocator, + *target_parser, + target_index_descriptor, + KMER_SIZE, + WINDOWS_SIZE, + true, // hash representations + FILTERING_PARAMETER); // filter parameter + target_index->wait_to_be_ready(); // find anchors & find overlaps auto matcher = Matcher::create_matcher(allocator, @@ -128,7 +130,19 @@ void process_batch(std::vector& query_index_descriptors, // print overlaps if (print) { - print_paf(overlaps, cigars, *query_parser, *target_parser, KMER_SIZE, print_mutex); +#ifdef GW_BUILD_HTSLIB + if (format == OutputFormat::PAF) + { +#endif + print_paf(overlaps, cigars, *query_parser, *target_parser, KMER_SIZE, print_mutex); +#ifdef GW_BUILD_HTSLIB + } + // SAM or BAM, depends on type of format + else + { + print_sam(overlaps, cigars, *query_parser, *target_parser, format, print_mutex); + } +#endif } } } @@ -140,11 +154,12 @@ void process_batch(std::vector& query_index_descriptors, int main(int argc, char** argv) { // parse command line options - int c = 0; - bool help = false; - bool print = false; + int c = 0; + bool help = false; + bool print = false; + OutputFormat format = OutputFormat::PAF; - while ((c = getopt(argc, argv, "hp")) != -1) + while ((c = getopt(argc, argv, "hpSB")) != -1) { switch (c) { @@ -154,6 +169,18 @@ int main(int argc, char** argv) case 'h': help = true; break; + case 'S': +#ifndef GW_BUILD_HTSLIB + throw std::runtime_error("ERROR: Argument -S cannot be used without htslib"); +#endif + format = OutputFormat::SAM; + break; + case 'B': +#ifndef GW_BUILD_HTSLIB + throw std::runtime_error("ERROR: Argument -B cannot be used without htslib"); +#endif + format = OutputFormat::BAM; + break; } } @@ -162,9 +189,11 @@ int main(int argc, char** argv) { std::cout << "CUDA Mapper API sample program. Runs minimizer-based approximate mapping" << std::endl; std::cout << "Usage:" << std::endl; - std::cout << "./sample_cudamapper [-p] [-h]" << std::endl; + std::cout << "./sample_cudamapper [-p] [-h] [-S] [-B]" << std::endl; std::cout << "-p : Print the overlaps to stdout" << std::endl; std::cout << "-h : Print help message" << std::endl; + std::cout << "-S : Print in SAM format" << std::endl; + std::cout << "-B : Print in BAM format" << std::endl; std::exit(0); } @@ -185,7 +214,7 @@ int main(int argc, char** argv) std::vector query_index_descriptors = initialize_batch(query_parser, allocator); std::vector target_index_descriptors = initialize_batch(target_parser, allocator); - process_batch(query_index_descriptors, target_index_descriptors, query_parser, target_parser, allocator, print); + process_batch(query_index_descriptors, target_index_descriptors, query_parser, target_parser, allocator, print, format); return 0; } diff --git a/cudamapper/src/application_parameters.cpp b/cudamapper/src/application_parameters.cpp index ee6d013bc..f7642ea60 100644 --- a/cudamapper/src/application_parameters.cpp +++ b/cudamapper/src/application_parameters.cpp @@ -23,6 +23,7 @@ #include #include #include +#include #include namespace claraparabricks @@ -59,12 +60,13 @@ ApplicationParameters::ApplicationParameters(int argc, char* argv[]) {"help", no_argument, 0, 'h'}, }; - std::string optstring = "k:w:d:m:i:t:F:a:r:l:b:z:RDQ:q:C:c:vh"; + std::string optstring = "k:w:d:m:i:t:F:a:r:l:b:z:RDQ:q:C:c:BSvh"; bool target_indices_in_host_memory_set = false; bool target_indices_in_device_memory_set = false; bool custom_filtering_parameter = false; int32_t argument = 0; + format = OutputFormat::PAF; while ((argument = getopt_long(argc, argv, optstring.c_str(), options, nullptr)) != -1) { switch (argument) @@ -131,10 +133,24 @@ ApplicationParameters::ApplicationParameters(int argc, char* argv[]) target_indices_in_device_memory = std::stoi(optarg); target_indices_in_device_memory_set = true; break; + case 'S': +#ifndef GW_BUILD_HTSLIB + throw std::runtime_error("ERROR: Argument -S cannot be used without htslib"); +#endif + format = OutputFormat::SAM; + break; + case 'B': +#ifndef GW_BUILD_HTSLIB + throw std::runtime_error("ERROR: Argument -B cannot be used without htslib"); +#endif + format = OutputFormat::BAM; + break; case 'v': print_version(); + exit(1); case 'h': help(0); + exit(1); default: exit(1); } @@ -355,6 +371,12 @@ void ApplicationParameters::help(int32_t exit_code) -c, --target-indices-in-device-memory number of target indices to keep in device memory [5])" << R"( + -S + print overlaps in SAM format" + << R"( + -B + print overlaps in BAM format" + << R"( -v, --version Version information)" << std::endl; diff --git a/cudamapper/src/application_parameters.hpp b/cudamapper/src/application_parameters.hpp index 22acfbfad..705d95c45 100644 --- a/cudamapper/src/application_parameters.hpp +++ b/cudamapper/src/application_parameters.hpp @@ -32,6 +32,9 @@ class FastaParser; namespace cudamapper { +// Forward declare enum for output type +enum class OutputFormat; + /// @brief application parameteres, default or passed through command line class ApplicationParameters { @@ -59,7 +62,8 @@ class ApplicationParameters int32_t query_indices_in_device_memory = 5; // q int32_t target_indices_in_host_memory = 10; // C int32_t target_indices_in_device_memory = 5; // c - bool all_to_all = false; + OutputFormat format; // default is PAF, S for SAM, and B for BAM + bool all_to_all = false; std::string query_filepath; std::string target_filepath; std::shared_ptr query_parser; diff --git a/cudamapper/src/cudamapper_utils.cpp b/cudamapper/src/cudamapper_utils.cpp index 8125874e8..269ef5080 100644 --- a/cudamapper/src/cudamapper_utils.cpp +++ b/cudamapper/src/cudamapper_utils.cpp @@ -38,7 +38,7 @@ std::vector split_into_kmers(const gw_string_view_t& s, const const std::size_t kmer_count = s.length() - kmer_size + 1; std::vector kmers; - if (s.length() < kmer_size) + if (get_size(s) < kmer_size) { kmers.push_back(s); return kmers; @@ -46,7 +46,7 @@ std::vector split_into_kmers(const gw_string_view_t& s, const for (std::size_t i = 0; i < kmer_count; i += stride) { - kmers.push_back(s.substr(i, i + kmer_size)); + kmers.push_back(s.substr(i, kmer_size)); } return kmers; } diff --git a/cudamapper/src/index.cu b/cudamapper/src/index.cu index 98c7064b4..168dbedd6 100644 --- a/cudamapper/src/index.cu +++ b/cudamapper/src/index.cu @@ -28,33 +28,33 @@ namespace genomeworks namespace cudamapper { -std::unique_ptr Index::create_index(DefaultDeviceAllocator allocator, - const io::FastaParser& parser, - const read_id_t first_read_id, - const read_id_t past_the_last_read_id, - const std::uint64_t kmer_size, - const std::uint64_t window_size, - const bool hash_representations, - const double filtering_parameter, - const cudaStream_t cuda_stream) +std::unique_ptr Index::create_index_async(DefaultDeviceAllocator allocator, + const io::FastaParser& parser, + const IndexDescriptor& descriptor, + const std::uint64_t kmer_size, + const std::uint64_t window_size, + const bool hash_representations, + const double filtering_parameter, + const cudaStream_t cuda_stream_generation, + const cudaStream_t cuda_stream_copy) { - GW_NVTX_RANGE(profiler, "create_index"); + GW_NVTX_RANGE(profiler, "create_index_async"); return std::make_unique>(allocator, parser, - first_read_id, - past_the_last_read_id, + descriptor, kmer_size, window_size, hash_representations, filtering_parameter, - cuda_stream); + cuda_stream_generation, + cuda_stream_copy); } -std::unique_ptr IndexHostCopyBase::create_cache(const Index& index, - const read_id_t first_read_id, - const std::uint64_t kmer_size, - const std::uint64_t window_size, - const cudaStream_t cuda_stream) +std::unique_ptr IndexHostCopyBase::create_host_copy_async(const Index& index, + const read_id_t first_read_id, + const std::uint64_t kmer_size, + const std::uint64_t window_size, + const cudaStream_t cuda_stream) { GW_NVTX_RANGE(profiler, "cache_D2H"); return std::make_unique(index, @@ -64,6 +64,16 @@ std::unique_ptr IndexHostCopyBase::create_cache(const Index& cuda_stream); } +IndexNotReadyException::IndexNotReadyException(const std::string& function_name) + : message_("Index::" + function_name + "() has been accessed before a call to wait_to_be_ready()") +{ +} + +const char* IndexNotReadyException::what() const noexcept +{ + return message_.c_str(); +} + } // namespace cudamapper } // namespace genomeworks diff --git a/cudamapper/src/index_cache.cu b/cudamapper/src/index_cache.cu index 4e82c7e31..b128d35a4 100644 --- a/cudamapper/src/index_cache.cu +++ b/cudamapper/src/index_cache.cu @@ -32,7 +32,76 @@ namespace genomeworks namespace cudamapper { -IndexCacheHost::IndexCacheHost(const bool same_query_and_target, +DeviceIndexCache::DeviceIndexCache(const CacheType cache_type, + HostIndexCache* host_cache) + : cache_type_(cache_type) + , host_cache_(host_cache) + , is_ready_(false) +{ + host_cache_->register_device_cache(cache_type_, + this); +} + +DeviceIndexCache::~DeviceIndexCache() +{ + host_cache_->deregister_device_cache(cache_type_, + this); +} + +void DeviceIndexCache::add_index(const IndexDescriptor index_descriptor, + std::shared_ptr device_index) +{ + cache_[index_descriptor] = device_index; +} + +std::shared_ptr DeviceIndexCache::get_index(const IndexDescriptor index_descriptor) const +{ + if (!is_ready()) + { + throw DeviceCacheNotReadyException(cache_type_, + index_descriptor); + } + + return get_index_no_check_if_ready(index_descriptor); +} + +std::shared_ptr DeviceIndexCache::get_index_no_check_if_ready(IndexDescriptor index_descriptor) const +{ + const auto index_iter = cache_.find(index_descriptor); + if (index_iter == cache_.end()) + { + throw IndexNotFoundException(cache_type_, + IndexNotFoundException::IndexLocation::device_cache, + index_descriptor); + } + return index_iter->second; +} + +bool DeviceIndexCache::has_index(const IndexDescriptor index_descriptor) const +{ + // TODO: use optional instead + return 0 != cache_.count(index_descriptor); +} + +void DeviceIndexCache::wait_for_data_to_be_ready() +{ + if (!is_ready()) + { + for (const auto& index_it : cache_) + { + index_it.second->wait_to_be_ready(); + } + + is_ready_ = true; + } +} + +bool DeviceIndexCache::is_ready() const +{ + return is_ready_; +} + +HostIndexCache::HostIndexCache(const bool same_query_and_target, genomeworks::DefaultDeviceAllocator allocator, std::shared_ptr query_parser, std::shared_ptr target_parser, @@ -40,7 +109,8 @@ IndexCacheHost::IndexCacheHost(const bool same_query_and_target, const std::uint64_t window_size, const bool hash_representations, const double filtering_parameter, - const cudaStream_t cuda_stream) + cudaStream_t cuda_stream_generation, + cudaStream_t cuda_stream_copy) : same_query_and_target_(same_query_and_target) , allocator_(allocator) , query_parser_(query_parser) @@ -49,254 +119,255 @@ IndexCacheHost::IndexCacheHost(const bool same_query_and_target, , window_size_(window_size) , hash_representations_(hash_representations) , filtering_parameter_(filtering_parameter) - , cuda_stream_(cuda_stream) + , cuda_stream_generation_(cuda_stream_generation) + , cuda_stream_copy_(cuda_stream_copy) { } -void IndexCacheHost::generate_query_cache_content(const std::vector& descriptors_of_indices_to_cache, - const std::vector& descriptors_of_indices_to_keep_on_device, - const bool skip_copy_to_host) -{ - generate_cache_content(descriptors_of_indices_to_cache, - descriptors_of_indices_to_keep_on_device, - skip_copy_to_host, - CacheSelector::query_cache); -} - -void IndexCacheHost::generate_target_cache_content(const std::vector& descriptors_of_indices_to_cache, - const std::vector& descriptors_of_indices_to_keep_on_device, - const bool skip_copy_to_host) -{ - generate_cache_content(descriptors_of_indices_to_cache, - descriptors_of_indices_to_keep_on_device, - skip_copy_to_host, - CacheSelector::target_cache); -} - -std::shared_ptr IndexCacheHost::get_index_from_query_cache(const IndexDescriptor& descriptor_of_index_to_cache) -{ - return get_index_from_cache(descriptor_of_index_to_cache, - CacheSelector::query_cache); -} - -std::shared_ptr IndexCacheHost::get_index_from_target_cache(const IndexDescriptor& descriptor_of_index_to_cache) -{ - return get_index_from_cache(descriptor_of_index_to_cache, - CacheSelector::target_cache); -} - -void IndexCacheHost::generate_cache_content(const std::vector& descriptors_of_indices_to_cache, - const std::vector& descriptors_of_indices_to_keep_on_device, - const bool skip_copy_to_host, - const CacheSelector which_cache) +void HostIndexCache::generate_content(const CacheType cache_type, + const std::vector& descriptors_of_indices_to_cache, + const std::vector& descriptors_of_indices_to_keep_on_device, + const bool skip_copy_to_host) { // skip_copy_to_host only makes sense if descriptors_of_indices_to_cache and descriptors_of_indices_to_keep_on_device are the same // otherwise some indices would be created and not saved on either host or device assert(!skip_copy_to_host || (descriptors_of_indices_to_cache == descriptors_of_indices_to_keep_on_device)); + assert(!descriptors_of_indices_to_cache.empty()); - cache_type_t& cache_to_edit = (CacheSelector::query_cache == which_cache) ? query_cache_ : target_cache_; - const cache_type_t& cache_to_check = (CacheSelector::query_cache == which_cache) ? target_cache_ : query_cache_; - device_cache_type_t& temp_device_cache_to_edit = (CacheSelector::query_cache == which_cache) ? query_temp_device_cache_ : target_temp_device_cache_; - const device_cache_type_t& temp_device_cache_to_check = (CacheSelector::query_cache == which_cache) ? target_temp_device_cache_ : query_temp_device_cache_; - const genomeworks::io::FastaParser* parser = (CacheSelector::query_cache == which_cache) ? query_parser_.get() : target_parser_.get(); + host_cache_t& this_cache = (CacheType::query_cache == cache_type) ? query_host_cache_ : target_host_cache_; + const host_cache_t& other_cache = (CacheType::query_cache == cache_type) ? target_host_cache_ : query_host_cache_; + device_cache_t& indices_kept_on_device = (CacheType::query_cache == cache_type) ? query_indices_kept_on_device_ : target_indices_kept_on_device_; + const genomeworks::io::FastaParser* parser = (CacheType::query_cache == cache_type) ? query_parser_.get() : target_parser_.get(); // convert descriptors_of_indices_to_keep_on_device into set for faster search std::unordered_set descriptors_of_indices_to_keep_on_device_set(begin(descriptors_of_indices_to_keep_on_device), end(descriptors_of_indices_to_keep_on_device)); - cache_type_t new_cache; - temp_device_cache_to_edit.clear(); // this should be empty by now anyway + host_cache_t new_cache; + indices_kept_on_device.clear(); // normally this should be empty anyway + + // In most cases index is generated on device and then moved to host. These two operations can be overlapped, i.e. while one index is being copied + // to host the next index can be generated. + // Index cache is expected to be larger than the available device memory, meaning it is not possible to keep all indices on device while they are + // being copied to host. In this implementation only two copies of index are kept on device: the one currently being generated and the one currently + // being copied to host (from the previous step). + + std::shared_ptr index_on_host = nullptr; + std::shared_ptr index_on_device = nullptr; + // Only one pair of (host, device) indices can be copied at a time. Whenever a copy should be started if these pointers are not null (= copy is in progress) + // wait for that current copy to be done first + std::shared_ptr index_on_host_copy_in_flight = nullptr; + std::shared_ptr index_on_device_copy_in_flight = nullptr; + + const bool host_copy_needed = !skip_copy_to_host; for (const IndexDescriptor& descriptor_of_index_to_cache : descriptors_of_indices_to_cache) { - // check if this index should be kept on device in addition to copying it to host - const bool keep_on_device = descriptors_of_indices_to_keep_on_device_set.count(descriptor_of_index_to_cache) != 0; + index_on_host = nullptr; + index_on_device = nullptr; - std::shared_ptr index_on_host = nullptr; - std::shared_ptr index_on_device = nullptr; + const bool device_copy_needed = descriptors_of_indices_to_keep_on_device_set.count(descriptor_of_index_to_cache) != 0; - if (same_query_and_target_) + // check if host copy already exists + + // check if index is already in this cache + auto index_in_this_cache = this_cache.find(descriptor_of_index_to_cache); + if (index_in_this_cache != this_cache.end()) + { + // index already cached + index_on_host = index_in_this_cache->second; + } + // if index not found in this cache and query and target input files are the same check the other cache as well + if (!index_on_host && same_query_and_target_) { - // check if the same index already exists in the other cache - auto existing_cache = cache_to_check.find(descriptor_of_index_to_cache); - if (existing_cache != cache_to_check.end()) + auto index_in_other_cache = other_cache.find(descriptor_of_index_to_cache); + if (index_in_other_cache != other_cache.end()) { - index_on_host = existing_cache->second; - if (keep_on_device) - { - auto existing_device_cache = temp_device_cache_to_check.find(descriptor_of_index_to_cache); - if (existing_device_cache != temp_device_cache_to_check.end()) - { - index_on_device = existing_device_cache->second; - } - else - { - index_on_device = index_on_host->copy_index_to_device(allocator_, cuda_stream_); - } - } + index_on_host = index_in_other_cache->second; } } - if (nullptr == index_on_host) + if (!index_on_host) { - // check if this index is already cached in this cache - auto existing_cache = cache_to_edit.find(descriptor_of_index_to_cache); - if (existing_cache != cache_to_edit.end()) + // create index + index_on_device = Index::create_index_async(allocator_, + *parser, + descriptor_of_index_to_cache, + kmer_size_, + window_size_, + hash_representations_, + filtering_parameter_, + cuda_stream_generation_, + cuda_stream_copy_); + index_on_device->wait_to_be_ready(); + + if (host_copy_needed) { - // index already cached - index_on_host = existing_cache->second; - if (keep_on_device) + // if a copy is already in progress wait for it to finish + if (index_on_host_copy_in_flight) { - index_on_device = index_on_host->copy_index_to_device(allocator_, cuda_stream_); - } - } - else - { - // create index - index_on_device = Index::create_index(allocator_, - *parser, - descriptor_of_index_to_cache.first_read(), - descriptor_of_index_to_cache.first_read() + descriptor_of_index_to_cache.number_of_reads(), - kmer_size_, - window_size_, - hash_representations_, - filtering_parameter_, - cuda_stream_); - // copy it to host memory - if (!skip_copy_to_host) - { - index_on_host = IndexHostCopy::create_cache(*index_on_device, - descriptor_of_index_to_cache.first_read(), - kmer_size_, - window_size_, - cuda_stream_); + assert(index_on_host_copy_in_flight && index_on_device_copy_in_flight); + index_on_host_copy_in_flight->finish_copying(); } + + index_on_host = IndexHostCopy::create_host_copy_async(*index_on_device, + descriptor_of_index_to_cache.first_read(), + kmer_size_, + window_size_, + cuda_stream_copy_); + + index_on_host_copy_in_flight = index_on_host; + index_on_device_copy_in_flight = index_on_device; } } - // save pointer to cached index - if (!skip_copy_to_host) + if (index_on_host) { - assert(nullptr != index_on_host); new_cache[descriptor_of_index_to_cache] = index_on_host; } - if (keep_on_device) + // Device copy of index is only saved if is already exists, i.e. if the index has been generated + // If the index has been found on host it won't be copied back to device at this point + // TODO: check whether this index is already present in device cache, this is not expected to happen frequently so performance gains are going to be small + if (device_copy_needed && index_on_device) { - temp_device_cache_to_edit[descriptor_of_index_to_cache] = index_on_device; + indices_kept_on_device[descriptor_of_index_to_cache] = index_on_device; } } - std::swap(new_cache, cache_to_edit); -} - -std::shared_ptr IndexCacheHost::get_index_from_cache(const IndexDescriptor& descriptor_of_index_to_cache, - const CacheSelector which_cache) -{ - std::shared_ptr index; - - const cache_type_t& host_cache = (CacheSelector::query_cache == which_cache) ? query_cache_ : target_cache_; - device_cache_type_t& temp_device_index_cache = (CacheSelector::query_cache == which_cache) ? query_temp_device_cache_ : target_temp_device_cache_; - - auto temp_device_index_cache_iter = temp_device_index_cache.find(descriptor_of_index_to_cache); - // check if index is present in device memory, copy from host if not - if (temp_device_index_cache_iter != temp_device_index_cache.end()) - { - index = temp_device_index_cache_iter->second; - // indices are removed from device cache after they have been used for the first time - temp_device_index_cache.erase(temp_device_index_cache_iter); - } - else + // wait for the last copy to finish + if (index_on_host_copy_in_flight) { - // TODO: throw custom exception if index not found - index = host_cache.at(descriptor_of_index_to_cache)->copy_index_to_device(allocator_, cuda_stream_); + assert(index_on_host_copy_in_flight && index_on_device_copy_in_flight); + index_on_host_copy_in_flight->finish_copying(); } - return index; -} - -IndexCacheDevice::IndexCacheDevice(const bool same_query_and_target, - std::shared_ptr index_cache_host) - : same_query_and_target_(same_query_and_target) - , index_cache_host_(index_cache_host) -{ -} - -void IndexCacheDevice::generate_query_cache_content(const std::vector& descriptors_of_indices_to_cache) -{ - generate_cache_content(descriptors_of_indices_to_cache, CacheSelector::query_cache); -} - -void IndexCacheDevice::generate_target_cache_content(const std::vector& descriptors_of_indices_to_cache) -{ - generate_cache_content(descriptors_of_indices_to_cache, CacheSelector::target_cache); -} - -std::shared_ptr IndexCacheDevice::get_index_from_query_cache(const IndexDescriptor& descriptor_of_index_to_cache) -{ - // TODO: throw custom exception if index not found - return query_cache_.at(descriptor_of_index_to_cache); + std::swap(new_cache, this_cache); } -std::shared_ptr IndexCacheDevice::get_index_from_target_cache(const IndexDescriptor& descriptor_of_index_to_cache) +std::shared_ptr HostIndexCache::start_copying_indices_to_device(const CacheType cache_type, + const std::vector& descriptors_of_indices_to_cache) { - // TODO: throw custom exception if index not found - return target_cache_.at(descriptor_of_index_to_cache); -} + const host_cache_t& host_cache = (CacheType::query_cache == cache_type) ? query_host_cache_ : target_host_cache_; + const std::vector& this_device_caches = (CacheType::query_cache == cache_type) ? query_device_caches_ : target_device_caches_; + const std::vector& other_device_caches = (CacheType::query_cache == cache_type) ? target_device_caches_ : query_device_caches_; + device_cache_t& indices_kept_on_device = (CacheType::query_cache == cache_type) ? query_indices_kept_on_device_ : target_indices_kept_on_device_; -void IndexCacheDevice::generate_cache_content(const std::vector& descriptors_of_indices_to_cache, - const CacheSelector which_cache) -{ - cache_type_t& cache_to_edit = (CacheSelector::query_cache == which_cache) ? query_cache_ : target_cache_; - const cache_type_t& cache_to_check = (CacheSelector::query_cache == which_cache) ? target_cache_ : query_cache_; + std::shared_ptr device_cache = std::make_shared(cache_type, + this); - cache_type_t new_cache; - - for (const IndexDescriptor& descriptor_of_index_to_cache : descriptors_of_indices_to_cache) + for (const IndexDescriptor& descriptor : descriptors_of_indices_to_cache) { + std::shared_ptr device_index = nullptr; - std::shared_ptr index = nullptr; + // check if index was kept on device after creation + auto index_kept_on_device = indices_kept_on_device.find(descriptor); + if (index_kept_on_device != indices_kept_on_device.end()) + { + device_index = index_kept_on_device->second; + indices_kept_on_device.erase(descriptor); + } - if (same_query_and_target_) + // check if value is already in this cache + if (!device_index) { - // check if the same index already exists in the other cache - auto existing_cache = cache_to_check.find(descriptor_of_index_to_cache); - if (existing_cache != cache_to_check.end()) + for (const DeviceIndexCache* const existing_cache : this_device_caches) { - index = existing_cache->second; + if (existing_cache != device_cache.get() && existing_cache->has_index(descriptor)) + { + device_index = existing_cache->get_index_no_check_if_ready(descriptor); + break; + } } } - if (nullptr == index) + // if query and target files are the same check the other index as well + if (!device_index && same_query_and_target_) { - // check if this index is already cached in this cache - auto existing_cache = cache_to_edit.find(descriptor_of_index_to_cache); - if (existing_cache != cache_to_edit.end()) + for (const DeviceIndexCache* const existing_cache : other_device_caches) { - // index already cached - index = existing_cache->second; - } - else - { - // index not already cached -> fetch it from index_cache_host_ - if (CacheSelector::query_cache == which_cache) - { - index = index_cache_host_->get_index_from_query_cache(descriptor_of_index_to_cache); - } - else + if (existing_cache->has_index(descriptor)) { - index = index_cache_host_->get_index_from_target_cache(descriptor_of_index_to_cache); + device_index = existing_cache->get_index_no_check_if_ready(descriptor); + break; } } } - assert(nullptr != index); + // if index has not been found on device copy it from host + if (!device_index) + { + const auto index_on_host_iter = host_cache.find(descriptor); + if (index_on_host_iter == host_cache.end()) + { + throw IndexNotFoundException(cache_type, + IndexNotFoundException::IndexLocation::host_cache, + descriptor); + } + device_index = index_on_host_iter->second->copy_index_to_device(allocator_, cuda_stream_copy_); + } - // save pointer to cached index - new_cache[descriptor_of_index_to_cache] = index; + assert(device_index); + device_cache->add_index(descriptor, + device_index); } - std::swap(new_cache, cache_to_edit); + return device_cache; +} + +void HostIndexCache::register_device_cache(const CacheType cache_type, + DeviceIndexCache* index_cache) +{ + assert(cache_type == CacheType::query_cache || cache_type == CacheType::target_cache); + + std::vector& device_caches = cache_type == CacheType::query_cache ? query_device_caches_ : target_device_caches_; + + device_caches.push_back(index_cache); +} + +void HostIndexCache::deregister_device_cache(const CacheType cache_type, + DeviceIndexCache* index_cache) +{ + assert(cache_type == CacheType::query_cache || cache_type == CacheType::target_cache); + + std::vector& device_caches = cache_type == CacheType::query_cache ? query_device_caches_ : target_device_caches_; + + auto new_end = std::remove(begin(device_caches), end(device_caches), index_cache); + device_caches.erase(new_end, end(device_caches)); +} + +IndexNotFoundException::IndexNotFoundException(const CacheType cache_type, + const IndexLocation index_location, + const IndexDescriptor index_descriptor) + : message_(std::string(cache_type == CacheType::query_cache ? "Query " : "Target ") + + "index not found in " + + std::string(index_location == IndexLocation::host_cache ? "host " : "device ") + + "cache. First read: " + + std::to_string(index_descriptor.first_read()) + + ", number of reads: " + + std::to_string(index_descriptor.number_of_reads())) +{ +} + +const char* IndexNotFoundException::what() const noexcept +{ + return message_.c_str(); +} + +DeviceCacheNotReadyException::DeviceCacheNotReadyException(const CacheType cache_type, + const IndexDescriptor index_descriptor) + : message_("Cache for " + + std::string(cache_type == CacheType::query_cache ? "query " : "target ") + + "index is not ready. First read: " + + std::to_string(index_descriptor.first_read()) + + ", number of reads: " + + std::to_string(index_descriptor.number_of_reads())) +{ +} + +const char* DeviceCacheNotReadyException::what() const noexcept +{ + return message_.c_str(); } } // namespace cudamapper diff --git a/cudamapper/src/index_cache.cuh b/cudamapper/src/index_cache.cuh index e3a8fa174..4dec7d9a7 100644 --- a/cudamapper/src/index_cache.cuh +++ b/cudamapper/src/index_cache.cuh @@ -16,7 +16,9 @@ #pragma once +#include #include +#include #include #include @@ -38,111 +40,195 @@ namespace cudamapper { class IndexHostCopyBase; +class HostIndexCache; -/// IndexCacheHost - Creates Indices, stores them in host memory and on demand copies them back to device memory +/// CacheType - Specifies if query or target cache +enum class CacheType +{ + query_cache, + target_cache +}; + +/// DeviceIndexCache - Owns copies of indices on device /// -/// The user tells cache which Indices to keep in cache using generate_query_cache_content() and generate_target_cache_content() and -/// retrieves indices using get_index_from_query_cache() and get_index_from_target_cache(). Trying to retrieve an -/// Index which was not previously stored in cache results in an exception -class IndexCacheHost +/// These object are created by HostIndexCache::start_copying_indices_to_device() +class DeviceIndexCache { public: /// \brief Constructor - /// \param same_query_and_target true means that both query and target are the same, meaning that if requested index exists in query cache it can also be used by target cache directly + /// \param cache_type + /// \param host_cache HostIndexCache that created this object + DeviceIndexCache(CacheType cache_type, + HostIndexCache* host_cache); + + DeviceIndexCache(const DeviceIndexCache&) = delete; + DeviceIndexCache(DeviceIndexCache&&) = delete; + DeviceIndexCache& operator=(const DeviceIndexCache&) = delete; + DeviceIndexCache& operator=(DeviceIndexCache&&) = delete; + + /// \brief Destructor + ~DeviceIndexCache(); + + /// \brief Returns requested index for which it is guarateed that it is ready, i.e. is has been fully copied from host memory is needed + /// Calling this function before wait_for_data_to_be_ready() results in an exception + /// \param index_descriptor + /// \throw IndexNotFoundException if requested index is not cached + /// \throw DeviceCacheNotReadyException is cache is not ready, i.e. wait_for_data_to_be_ready() has not been called yet + /// \return requested index + std::shared_ptr get_index(IndexDescriptor index_descriptor) const; + + /// \brief Returns whether given index is present in cache + /// \param index_descriptor + /// \return is given index present in cache + bool has_index(IndexDescriptor index_descriptor) const; + + /// \brief Waits for indices to be copied from host memory. Must be called before get_index() + void wait_for_data_to_be_ready(); + + /// \brief Returns whether indices have been copied to device and get_index() can be called, i.e. whether wait_for_data_to_be_ready() has already been called + /// \return whether indices have been copied to device + bool is_ready() const; + +private: + friend HostIndexCache; + + using device_cache_t = std::unordered_map, + IndexDescriptorHash>; + + /// \brief Adds index to cache + /// To be called by HostIndexCache::start_copying_indices_to_device() + /// \param index_descriptor + /// \param device_index + void add_index(IndexDescriptor index_descriptor, + std::shared_ptr device_index); + + /// \brief Returns requested index, returned index might not be ready and has to be synchronized directly + /// \param index_descriptor + /// \throw IndexNotFoundException if requested index is not cached + /// \return requested index + std::shared_ptr get_index_no_check_if_ready(IndexDescriptor index_descriptor) const; + + device_cache_t cache_; + + CacheType cache_type_; + // HostIndexCache which created this DeviceIndexCache + HostIndexCache* host_cache_; + + // wait_for_data_to_be_ready + bool is_ready_; +}; + +/// HostIndexCache - Creates indices, stores them in host memory and on demands moves them to device memory +/// +/// Class contains separate caches for query and target. The user chooses between query and target by specifying CacheType in function calls. +/// The user generates indices and stores them in host memory using generate_content(). The user then copies some of those indices +/// to device memory using start_copying_indices_to_device() and the function returns a pointer to DeviceIndexCache. To wait for indices to be +/// fully copied one should call DeviceIndexCache::wait_for_data_to_be_ready(). +/// It is user's responsibility to make sure that indices requested by start_copying_indices_to_device() were generated by generate_content(). +/// Memory copy to device is done asynchronously, the user should make sure that every call to start_copying_indices_to_device() is +/// accompanied by a call DeviceIndexCache::wait_for_data_to_be_ready(). +/// The class tries to minimize the number of index creation and movements, e.g. by reusing already existing indices, but not guarantees are given. +class HostIndexCache +{ +public: + /// \brief Constructor only initializes cache, no index is generated at this point, generate_content() does that + /// + /// \param same_query_and_target true means that both query and target files are the same, meaning that if some index exists in query cache it can also be used by target cache directly /// \param allocator allocator to use for device arrays /// \param query_parser /// \param target_parser - /// \param kmer_size // see Index - /// \param window_size // see Index - /// \param hash_representations // see Index - /// \param filtering_parameter // see Index - /// \param cuda_stream // device memory used for Index copy will only we freed up once all previously scheduled work on this stream has finished - IndexCacheHost(bool same_query_and_target, + /// \param kmer_size see Index + /// \param window_size see Index + /// \param hash_representations see Index + /// \param filtering_parameter see Index + /// \param cuda_stream_generation index generation is done one this stream, device memory in resulting device copies of index will only we freed once all previously scheduled work on this stream has finished + /// \param cuda_stream_copy D2H and H2D copies of indices will be done on this stream, device memory in resulting device copies of index will only we freed once all previously scheduled work on this stream has finished + HostIndexCache(bool same_query_and_target, genomeworks::DefaultDeviceAllocator allocator, std::shared_ptr query_parser, std::shared_ptr target_parser, std::uint64_t kmer_size, std::uint64_t window_size, - bool hash_representations = true, - double filtering_parameter = 1.0, - cudaStream_t cuda_stream = 0); - - IndexCacheHost(const IndexCacheHost&) = delete; - IndexCacheHost& operator=(const IndexCacheHost&) = delete; - IndexCacheHost(IndexCacheHost&&) = delete; - IndexCacheHost& operator=(IndexCacheHost&&) = delete; - ~IndexCacheHost() = default; - - /// \brief Discards previously cached query Indices, creates new Indices and copies them to host memory + bool hash_representations = true, + double filtering_parameter = 1.0, + cudaStream_t cuda_stream_generation = 0, + cudaStream_t cuda_stream_copy = 0); + + HostIndexCache(const HostIndexCache&) = delete; + HostIndexCache(HostIndexCache&&) = delete; + HostIndexCache& operator=(const HostIndexCache&) = delete; + HostIndexCache& operator=(HostIndexCache&&) = delete; + ~HostIndexCache() = default; + + /// \brief Generates indices on device and copies them to host memory /// - /// Expected usage pattern is to call generate_query_cache_content() with certain index descriptors and then immediately retrieve some of them. - /// To avoid immediately copying back those indices from host to device it is possible to specify descriptors_of_indices_to_keep_on_device - // which will be copied to host, but also kept on device until retrieved for the first time using get_index_from_query_cache + /// If index already exists on host is may be reused. + /// Indices from descriptors_of_indices_to_keep_on_device will be kept on device in addition to being to host. This is useful if the same indices + /// are going to be requested by start_copying_indices_to_device() immediately after this call + /// If skip_copy_to_host is true indices are going to be kept on device and not copied to host. In that case descriptors_of_indices_to_cache must + /// be equal to descriptors_of_indices_to_keep_on_device and there must be only one call to start_copying_indices_to_device() with exactly these indices + /// Calling this function invalidates any previously cached data for the same cache type /// - /// \param descriptors_of_indices_to_cache descriptors on indices to keep in host memory - /// \param descriptors_of_indices_to_keep_on_device descriptors of indices to keep in device memory in addition to host memory until retrieved for the first time - /// \param skip_copy_to_host this option should be used if descriptors_of_indices_to_cache == descriptors_of_indices_to_keep_on_device and if each index will be queried only once, it's usefull for small cases where host cache isn't actually needed - void generate_query_cache_content(const std::vector& descriptors_of_indices_to_cache, - const std::vector& descriptors_of_indices_to_keep_on_device = {}, - bool skip_copy_to_host = false); - - /// \brief Discards previously cached target Indices, creates new Indices and copies them to host memory + /// \param cache_type + /// \param descriptors_of_indices_to_cache + /// \param descriptors_of_indices_to_keep_on_device + /// \param skip_copy_to_host + void generate_content(CacheType cache_type, + const std::vector& descriptors_of_indices_to_cache, + const std::vector& descriptors_of_indices_to_keep_on_device = {}, + bool skip_copy_to_host = false); + + /// \brief Begins copying indices to device /// - /// Expected usage pattern is to call generate_target_cache_content() with certain index descriptors and then immediately retrieve some of them. - /// To avoid immediately copying back those indices from host to device it is possible to specify descriptors_of_indices_to_keep_on_device - /// which will be copied to host, but also kept on device until retrieved for the first time using get_index_from_taget_cache + /// If index already exists on device it may be reused. + /// This copy is done asynchronously. Function returns a DeviceIndexCache object which should be used to access the indices. + /// Copy to device is finised by calling DeviceIndexCache::wait_for_data_to_be_ready(). + /// The user should make sure that every call to start_copying_indices_to_device() is accompanied by a call to DeviceIndexCache::wait_for_data_to_be_ready() /// - /// \param descriptors_of_indices_to_cache descriptors on indices to keep in host memory - /// \param descriptors_of_indices_to_keep_on_device descriptors of indices to keep in device memory in addition to host memory until retrieved for the first time - /// \param skip_copy_to_host this option should be used if descriptors_of_indices_to_cache == descriptors_of_indices_to_keep_on_device and if each index will be queried only once, it's usefull for small cases where host cache isn't actually needed - void generate_target_cache_content(const std::vector& descriptors_of_indices_to_cache, - const std::vector& descriptors_of_indices_to_keep_on_device = {}, - bool skip_copy_to_host = false); - - /// \brief Copies request Index to device memory - /// throws if that index is currently not in cache - std::shared_ptr get_index_from_query_cache(const IndexDescriptor& descriptor_of_index_to_cache); - - /// \brief Copies request Index to device memory - /// throws if that index is currently not in cache - std::shared_ptr get_index_from_target_cache(const IndexDescriptor& descriptor_of_index_to_cache); + /// \param cache_type + /// \param descriptors_of_indices_to_cache + /// \throw IndexNotFoundException if an index that is not cached by call to generate_content() is requested + /// \return DeviceIndexCache object + std::shared_ptr start_copying_indices_to_device(CacheType cache_type, + const std::vector& descriptors_of_indices_to_cache); private: - using cache_type_t = std::unordered_map, IndexDescriptorHash>; - using device_cache_type_t = std::unordered_map, - IndexDescriptorHash>; + using device_cache_t = std::unordered_map, + IndexDescriptorHash>; - enum class CacheSelector - { - query_cache, - target_cache - }; + /// \brief Registers DeviceIndexCache object + /// To be called by the constructor of DeviceIndexCache + /// \param cache_type + /// \param index_cache + void register_device_cache(CacheType cache_type, + DeviceIndexCache* index_cache); - /// \brief Discards previously cached Indices, creates new Indices and copies them to host memory - /// Uses which_cache to determine if it should be working on query of target indices - /// - /// If same_query_and_target_ is true function checks the other cache to see if that index is already in cache - void generate_cache_content(const std::vector& descriptors_of_indices_to_cache, - const std::vector& descriptors_of_indices_to_keep_on_device, - bool skip_copy_to_host, - CacheSelector which_cache); - - /// \brief Fetches requested index - /// Copies index from host to device memory, unless index is saved in temp device cache - /// If that is the case it returs that device copy are removes it from temp device cache - std::shared_ptr get_index_from_cache(const IndexDescriptor& descriptor_of_index_to_cache, - CacheSelector which_cache); - - /// Host copies of indices - cache_type_t query_cache_; - cache_type_t target_cache_; - /// User can instruct cache to also keep certain indices in device memory until retrieved for the first time - device_cache_type_t query_temp_device_cache_; - device_cache_type_t target_temp_device_cache_; + /// \brief Deregisters DeviceIndexCache object + /// To be called by the destructor of DeviceIndexCache + /// \param cache_type + /// \param index_cache + void deregister_device_cache(CacheType cache_type, + DeviceIndexCache* index_cache); + + // Indices kept on host + host_cache_t query_host_cache_; + host_cache_t target_host_cache_; + + // Indices kept of device because of descriptors_of_indices_to_keep_on_device + device_cache_t query_indices_kept_on_device_; + device_cache_t target_indices_kept_on_device_; + + // Currently existing DeviceIndexCaches created by this HostIndexCache + std::vector query_device_caches_; + std::vector target_device_caches_; const bool same_query_and_target_; genomeworks::DefaultDeviceAllocator allocator_; @@ -152,68 +238,51 @@ private: const std::uint64_t window_size_; const bool hash_representations_; const double filtering_parameter_; - const cudaStream_t cuda_stream_; + const cudaStream_t cuda_stream_generation_; + const cudaStream_t cuda_stream_copy_; }; -/// IndexCacheDevice - Keeps copies of Indices in device memory -/// -/// The user tells cache which Indices to keep in cache using generate_query_cache_content() and generate_target_cache_content() and -/// retrieves indices using get_index_from_query_cache() and get_index_from_target_cache(). Trying to retrieve an -/// Index which was not previously stored in cache results in an exception. -/// -/// IndexCacheDevice relies on IndexCacheHost to provide actual indices for caching -class IndexCacheDevice +/// IndexNotFoundException - Exception to be thrown if Index is reuqsted, but not found +class IndexNotFoundException : public std::exception { public: - /// \brief Constructor - /// \param same_query_and_target true means that both query and target are the same, meaning that if requested index exists in query cache it can also be used by target cache directly - /// \param index_cache_host underlying host cache to get the indices from - IndexCacheDevice(bool same_query_and_target, - std::shared_ptr index_cache_host); - - IndexCacheDevice(const IndexCacheDevice&) = delete; - IndexCacheDevice& operator=(const IndexCacheDevice&) = delete; - IndexCacheDevice(IndexCacheDevice&&) = delete; - IndexCacheDevice& operator=(IndexCacheDevice&&) = delete; - ~IndexCacheDevice() = default; - - /// \brief Discards previously cached query Indices, creates new Indices and copies them to host memory - void generate_query_cache_content(const std::vector& descriptors_of_indices_to_cache); - - /// \brief Discards previously cached target Indices, creates new Indices and copies them to host memory - void generate_target_cache_content(const std::vector& descriptors_of_indices_to_cache); + /// IndexLocation - Was the Index requested from host or device cache + enum class IndexLocation + { + host_cache, + device_cache + }; - /// \brief Copies request Index to device memory - /// throws if that index is currently not in cache - std::shared_ptr get_index_from_query_cache(const IndexDescriptor& descriptor_of_index_to_cache); + /// \brief constructor + /// \param cache_type was Index requested from host or device cache + /// \param index_location + /// \param index_descriptor + IndexNotFoundException(CacheType cache_type, + IndexLocation index_location, + IndexDescriptor index_descriptor); - /// \brief Copies request Index to device memory - /// throws if that index is currently not in cache - std::shared_ptr get_index_from_target_cache(const IndexDescriptor& descriptor_of_index_to_cache); + /// \brief Returns the error message of the exception + const char* what() const noexcept override; private: - using cache_type_t = std::unordered_map, - IndexDescriptorHash>; - - enum class CacheSelector - { - query_cache, - target_cache - }; + const std::string message_; +}; - /// \brief Discards previously cached Indices and caches new ones - /// Uses which_cache to determine if it should be working on query of target indices - /// - /// If same_query_and_target_ is true function checks the other cache to see if that index is already in cache - void generate_cache_content(const std::vector& descriptors_of_indices_to_cache, - CacheSelector which_cache); +/// DeviceCacheNotReadyException - Exception ot be thrown when an index is requested before it has been copied completely +class DeviceCacheNotReadyException : public std::exception +{ +public: + /// \brief constructor + /// \param cache_type + /// \param index_descriptor + DeviceCacheNotReadyException(CacheType cache_type, + IndexDescriptor index_descriptor); - cache_type_t query_cache_; - cache_type_t target_cache_; + /// \brief Returns the error message of the exception + const char* what() const noexcept override; - const bool same_query_and_target_; - std::shared_ptr index_cache_host_; +private: + const std::string message_; }; } // namespace cudamapper diff --git a/cudamapper/src/index_gpu.cuh b/cudamapper/src/index_gpu.cuh index 7b0f7a427..37e2ac487 100644 --- a/cudamapper/src/index_gpu.cuh +++ b/cudamapper/src/index_gpu.cuh @@ -62,7 +62,9 @@ template class IndexGPU : public Index { public: - /// \brief Constructor whcih constucts a new index + /// \brief Constructor which generates a new index + /// + /// Generation is done asynchronously and one should call wait_to_be_ready() before using the object /// /// \param parser parser for the whole input file (part that goes into this index is determined by first_read_id and past_the_last_read_id) /// \param first_read_id read_id of the first read to the included in this index @@ -71,73 +73,102 @@ public: /// \param window_size w - the length of the sliding window used to find sketch elements (i.e. the number of adjacent k-mers in a window, adjacent = shifted by one basepair) /// \param hash_representations - if true, hash kmer representations /// \param filtering_parameter - filter out all representations for which number_of_sketch_elements_with_that_representation/total_skech_elements >= filtering_parameter, filtering_parameter == 1.0 disables filtering - /// \param cuda_stream CUDA stream on which the work is to be done. Device arrays are also associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor is done + /// \param cuda_stream_generation CUDA stream on which index is generated. Device arrays are associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor has been done + /// \param cuda_stream_copy CUDA stream on which the index is copied to host if needed. Device arrays are associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor has been done IndexGPU(DefaultDeviceAllocator allocator, const io::FastaParser& parser, - const read_id_t first_read_id, - const read_id_t past_the_last_read_id, + const IndexDescriptor& descriptor, const std::uint64_t kmer_size, const std::uint64_t window_size, - const bool hash_representations = true, - const double filtering_parameter = 1.0, - const cudaStream_t cuda_stream = 0); + const bool hash_representations = true, + const double filtering_parameter = 1.0, + const cudaStream_t cuda_stream_generation = 0, + const cudaStream_t cuda_stream_copy = 0); /// \brief Constructor which copies the index from host copy /// + /// Copy is done asynchronously and one should call wait_to_be_ready() before using the object + /// /// \param allocator is pointer to asynchronous device allocator /// \param index_host_copy is a copy of index for a set of reads which has been previously computed and stored on the host. /// \param cuda_stream CUDA stream on which the work is to be done. Device arrays are also associated with this stream and will not be freed at least until all work issued on this stream before calling their destructor is done IndexGPU(DefaultDeviceAllocator allocator, - const IndexHostCopy& index_host_copy, + const IndexHostCopy* const index_host_copy, const cudaStream_t cuda_stream = 0); /// \brief returns an array of representations of sketch elements + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of representations of sketch elements const device_buffer& representations() const override; /// \brief returns an array of reads ids for sketch elements + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of reads ids for sketch elements const device_buffer& read_ids() const override; /// \brief returns an array of starting positions of sketch elements in their reads + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of starting positions of sketch elements in their reads const device_buffer& positions_in_reads() const override; /// \brief returns an array of directions in which sketch elements were read + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array of directions in which sketch elements were read const device_buffer& directions_of_reads() const override; /// \brief returns an array where each representation is recorder only once, sorted by representation + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return an array where each representation is recorder only once, sorted by representation const device_buffer& unique_representations() const override; /// \brief returns first occurrence of corresponding representation from unique_representations() in data arrays, plus one more element with the total number of sketch elements + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return first occurrence of corresponding representation from unique_representations() in data arrays, plus one more element with the total number of sketch elements const device_buffer& first_occurrence_of_representations() const override; /// \brief returns number of reads in input data + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return number of reads in input data read_id_t number_of_reads() const override; /// \brief returns smallest read_id in index + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return smallest read_id in index (0 if empty index) read_id_t smallest_read_id() const override; /// \brief returns largest read_id in index + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return largest read_id in index (0 if empty index) read_id_t largest_read_id() const override; /// \brief returns length of the longest read in this index + /// \throw IndexNotReadyException if called before wait_to_be_ready() /// \return length of the longest read in this index position_in_read_t number_of_basepairs_in_longest_read() const override; + /// \brief checks if index is ready to be used on this device, index might not be ready if its creation or copy from host is asynchronous + /// \return whether the index is ready to be used + bool is_ready() const override; + + /// \brief if is_ready() is true returns immediately, blocks until it becomes ready otherwise + void wait_to_be_ready() override; + private: + /// WayOfConstruciton - has IndexGPU been created by generation or copy from host copy + enum class WayOfConstruciton + { + generation, + copy + }; + /// \brief generates the index void generate_index(const io::FastaParser& query_parser, const read_id_t first_read_id, const read_id_t past_the_last_read_id, const bool hash_representations, - const double filtering_parameter); + const double filtering_parameter, + DefaultDeviceAllocator allocator, + const cudaStream_t cuda_stream); device_buffer representations_d_; device_buffer read_ids_d_; @@ -154,11 +185,15 @@ private: const std::uint64_t window_size_ = 0; read_id_t number_of_reads_ = 0; position_in_read_t number_of_basepairs_in_longest_read_ = 0; + const WayOfConstruciton way_of_construciton_; - // CUDA stream on which the work is to be done and device arrays are to be associated with - cudaStream_t cuda_stream_; + // has index generation finished + bool is_ready_; + // if index is not generated but copied from the host a pointer to it is saved here + const IndexHostCopy* const index_host_copy_source_; - DefaultDeviceAllocator allocator_; + // only important is using generating constructor, ignored in copying constructor + cudaStream_t cuda_stream_generation_; }; namespace details @@ -555,154 +590,217 @@ void filter_out_most_common_representations(DefaultDeviceAllocator allocator, template IndexGPU::IndexGPU(DefaultDeviceAllocator allocator, const io::FastaParser& parser, - const read_id_t first_read_id, - const read_id_t past_the_last_read_id, + const IndexDescriptor& descriptor, const std::uint64_t kmer_size, const std::uint64_t window_size, const bool hash_representations, const double filtering_parameter, - const cudaStream_t cuda_stream) - : first_read_id_(first_read_id) + const cudaStream_t cuda_stream_generation, + const cudaStream_t cuda_stream_copy) + : first_read_id_(descriptor.first_read()) , kmer_size_(kmer_size) , window_size_(window_size) , number_of_reads_(0) , number_of_basepairs_in_longest_read_(0) - , allocator_(allocator) - , representations_d_(allocator) - , read_ids_d_(allocator) - , positions_in_reads_d_(allocator) - , directions_of_reads_d_(allocator) - , unique_representations_d_(allocator) - , first_occurrence_of_representations_d_(allocator) - , cuda_stream_(cuda_stream) + , representations_d_(0, allocator, cuda_stream_generation, cuda_stream_copy) + , read_ids_d_(0, allocator, cuda_stream_generation, cuda_stream_copy) + , positions_in_reads_d_(0, allocator, cuda_stream_generation, cuda_stream_copy) + , directions_of_reads_d_(0, allocator, cuda_stream_generation, cuda_stream_copy) + , unique_representations_d_(0, allocator, cuda_stream_generation, cuda_stream_copy) + , first_occurrence_of_representations_d_(0, allocator, cuda_stream_generation, cuda_stream_copy) + , way_of_construciton_(WayOfConstruciton::generation) + , is_ready_(false) // set to true in wait_to_be_ready() + , index_host_copy_source_(nullptr) + , cuda_stream_generation_(cuda_stream_generation) { generate_index(parser, first_read_id_, - past_the_last_read_id, + first_read_id_ + descriptor.number_of_reads(), hash_representations, - filtering_parameter); - - // This is not completely necessary, but if removed one has to make sure that the next step - // uses the same stream or that sync is done in caller - GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream_)); + filtering_parameter, + allocator, + cuda_stream_generation); } template IndexGPU::IndexGPU(DefaultDeviceAllocator allocator, - const IndexHostCopy& index_host_copy, + const IndexHostCopy* const index_host_copy, const cudaStream_t cuda_stream) - : first_read_id_(index_host_copy.first_read_id()) - , kmer_size_(index_host_copy.kmer_size()) - , window_size_(index_host_copy.window_size()) - , allocator_(allocator) - , representations_d_(allocator) - , read_ids_d_(allocator) - , positions_in_reads_d_(allocator) - , directions_of_reads_d_(allocator) - , unique_representations_d_(allocator) - , first_occurrence_of_representations_d_(allocator) - , cuda_stream_(cuda_stream) + : first_read_id_(index_host_copy->first_read_id()) + , kmer_size_(index_host_copy->kmer_size()) + , window_size_(index_host_copy->window_size()) + , representations_d_(index_host_copy->representations().size, allocator, cuda_stream) + , read_ids_d_(index_host_copy->read_ids().size, allocator, cuda_stream) + , positions_in_reads_d_(index_host_copy->positions_in_reads().size, allocator, cuda_stream) + , directions_of_reads_d_(index_host_copy->directions_of_reads().size, allocator, cuda_stream) + , unique_representations_d_(index_host_copy->unique_representations().size, allocator, cuda_stream) + , first_occurrence_of_representations_d_(index_host_copy->first_occurrence_of_representations().size, allocator, cuda_stream) + , way_of_construciton_(WayOfConstruciton::copy) + , is_ready_(false) // set to true in wait_to_be_ready() + , index_host_copy_source_(index_host_copy) + , cuda_stream_generation_(cuda_stream) { GW_NVTX_RANGE(profiler, "IndexGPU::constructor_copy_from_IndexHostCopy"); - number_of_reads_ = index_host_copy.number_of_reads(); - number_of_basepairs_in_longest_read_ = index_host_copy.number_of_basepairs_in_longest_read(); - - //H2D- representations_d_ = index_host_copy.representations(); - representations_d_.clear_and_resize(index_host_copy.representations().size()); - cudautils::device_copy_n(index_host_copy.representations().data(), index_host_copy.representations().size(), representations_d_.data(), cuda_stream); - - //H2D- read_ids_d_ = index_host_copy.read_ids(); - read_ids_d_.clear_and_resize(index_host_copy.read_ids().size()); - cudautils::device_copy_n(index_host_copy.read_ids().data(), index_host_copy.read_ids().size(), read_ids_d_.data(), cuda_stream); - - //H2D- positions_in_reads_d_ = index_host_copy.positions_in_reads(); - positions_in_reads_d_.clear_and_resize(index_host_copy.positions_in_reads().size()); - cudautils::device_copy_n(index_host_copy.positions_in_reads().data(), index_host_copy.positions_in_reads().size(), positions_in_reads_d_.data(), cuda_stream); + number_of_reads_ = index_host_copy->number_of_reads(); + number_of_basepairs_in_longest_read_ = index_host_copy->number_of_basepairs_in_longest_read(); - //H2D- directions_of_reads_d_ = index_host_copy.directions_of_reads(); - directions_of_reads_d_.clear_and_resize(index_host_copy.directions_of_reads().size()); - cudautils::device_copy_n(index_host_copy.directions_of_reads().data(), index_host_copy.directions_of_reads().size(), directions_of_reads_d_.data(), cuda_stream); - - //H2D- unique_representations_d_ = index_host_copy.unique_representations(); - unique_representations_d_.clear_and_resize(index_host_copy.unique_representations().size()); - cudautils::device_copy_n(index_host_copy.unique_representations().data(), index_host_copy.unique_representations().size(), unique_representations_d_.data(), cuda_stream); - - //H2D- first_occurrence_of_representations_d_ = index_host_copy.first_occurrence_of_representations(); - first_occurrence_of_representations_d_.clear_and_resize(index_host_copy.first_occurrence_of_representations().size()); - cudautils::device_copy_n(index_host_copy.first_occurrence_of_representations().data(), index_host_copy.first_occurrence_of_representations().size(), first_occurrence_of_representations_d_.data(), cuda_stream); - - // This is not completely necessary, but if removed one has to make sure that the next step - // uses the same stream or that sync is done in caller - GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream_)); + cudautils::device_copy_n(index_host_copy->representations().data, index_host_copy->representations().size, representations_d_.data(), cuda_stream); + cudautils::device_copy_n(index_host_copy->read_ids().data, index_host_copy->read_ids().size, read_ids_d_.data(), cuda_stream); + cudautils::device_copy_n(index_host_copy->positions_in_reads().data, index_host_copy->positions_in_reads().size, positions_in_reads_d_.data(), cuda_stream); + cudautils::device_copy_n(index_host_copy->directions_of_reads().data, index_host_copy->directions_of_reads().size, directions_of_reads_d_.data(), cuda_stream); + cudautils::device_copy_n(index_host_copy->unique_representations().data, index_host_copy->unique_representations().size, unique_representations_d_.data(), cuda_stream); + cudautils::device_copy_n(index_host_copy->first_occurrence_of_representations().data, index_host_copy->first_occurrence_of_representations().size, first_occurrence_of_representations_d_.data(), cuda_stream); } template const device_buffer& IndexGPU::representations() const { + if (!is_ready()) + { + throw IndexNotReadyException("representations"); + } + return representations_d_; }; template const device_buffer& IndexGPU::read_ids() const { + if (!is_ready()) + { + throw IndexNotReadyException("read_ids"); + } + return read_ids_d_; } template const device_buffer& IndexGPU::positions_in_reads() const { + if (!is_ready()) + { + throw IndexNotReadyException("positions_in_reads"); + } + return positions_in_reads_d_; } template const device_buffer& IndexGPU::directions_of_reads() const { + if (!is_ready()) + { + throw IndexNotReadyException("directions_of_reads"); + } + return directions_of_reads_d_; } template const device_buffer& IndexGPU::unique_representations() const { + if (!is_ready()) + { + throw IndexNotReadyException("unique_representations"); + } + return unique_representations_d_; } template const device_buffer& IndexGPU::first_occurrence_of_representations() const { + if (!is_ready()) + { + throw IndexNotReadyException("first_occurrence_of_representations"); + } + return first_occurrence_of_representations_d_; } template read_id_t IndexGPU::number_of_reads() const { + if (!is_ready()) + { + throw IndexNotReadyException("number_of_reads"); + } + return number_of_reads_; } template read_id_t IndexGPU::smallest_read_id() const { + if (!is_ready()) + { + throw IndexNotReadyException("smallest_read_id"); + } + return number_of_reads_ > 0 ? first_read_id_ : 0; } template read_id_t IndexGPU::largest_read_id() const { + if (!is_ready()) + { + throw IndexNotReadyException("largest_read_id"); + } + return number_of_reads_ > 0 ? first_read_id_ + number_of_reads_ - 1 : 0; } template position_in_read_t IndexGPU::number_of_basepairs_in_longest_read() const { + if (!is_ready()) + { + throw IndexNotReadyException("number_of_basepairs_in_longest_read"); + } + return number_of_basepairs_in_longest_read_; } +template +bool IndexGPU::is_ready() const +{ + return is_ready_; +} + +template +void IndexGPU::wait_to_be_ready() +{ + // if index is not ready for usage wait for it to become ready + if (!is_ready()) + { + if (WayOfConstruciton::generation == way_of_construciton_) + { + GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream_generation_)); + } + else if (WayOfConstruciton::copy == way_of_construciton_) + { + assert(index_host_copy_source_); + index_host_copy_source_->finish_copying(); + } + else + { + assert(!"unsupported value of WayOfConstruciton"); + } + + is_ready_ = true; + } +} + template void IndexGPU::generate_index(const io::FastaParser& parser, const read_id_t first_read_id, const read_id_t past_the_last_read_id, const bool hash_representations, - const double filtering_parameter) + const double filtering_parameter, + DefaultDeviceAllocator allocator, + const cudaStream_t cuda_stream) { GW_NVTX_RANGE(profiler, "IndexGPU::generate_index"); @@ -778,24 +876,24 @@ void IndexGPU::generate_index(const io::FastaParser& parser, } // move basepairs to the device - device_buffer read_id_to_basepairs_section_d(read_id_to_basepairs_section_h.size(), allocator_, cuda_stream_); - device_buffer merged_basepairs_d(merged_basepairs_h.size(), allocator_, cuda_stream_); + device_buffer read_id_to_basepairs_section_d(read_id_to_basepairs_section_h.size(), allocator, cuda_stream); + device_buffer merged_basepairs_d(merged_basepairs_h.size(), allocator, cuda_stream); { GW_NVTX_RANGE(profiler, "IndexGPU::generate_index::move_basepairs_to_gpu"); cudautils::device_copy_n(read_id_to_basepairs_section_h.data(), read_id_to_basepairs_section_h.size(), read_id_to_basepairs_section_d.data(), - cuda_stream_); // H2D + cuda_stream); // H2D cudautils::device_copy_n(merged_basepairs_h.data(), merged_basepairs_h.size(), merged_basepairs_d.data(), - cuda_stream_); // H2D + cuda_stream); // H2D } // sketch elements get generated here - auto sketch_elements = SketchElementImpl::generate_sketch_elements(allocator_, + auto sketch_elements = SketchElementImpl::generate_sketch_elements(allocator, local_to_global_read_id.size(), // number of valid reads kmer_size_, window_size_, @@ -804,9 +902,9 @@ void IndexGPU::generate_index(const io::FastaParser& parser, read_id_to_basepairs_section_h, read_id_to_basepairs_section_d, hash_representations, - cuda_stream_); + cuda_stream); - GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream_)); + GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream)); merged_basepairs_h.clear(); merged_basepairs_h.shrink_to_fit(); @@ -824,7 +922,7 @@ void IndexGPU::generate_index(const io::FastaParser& parser, // TODO: consider using a CUB radix sort based function here { GW_NVTX_RANGE(profiler, "IndexGPU::generate_index::sort_minimizers"); - thrust::stable_sort_by_key(thrust::cuda::par(allocator_).on(cuda_stream_), + thrust::stable_sort_by_key(thrust::cuda::par(allocator).on(cuda_stream), std::begin(generated_representations_d), std::end(generated_representations_d), std::begin(generated_rest_d)); @@ -841,23 +939,23 @@ void IndexGPU::generate_index(const io::FastaParser& parser, { GW_NVTX_RANGE(profiler, "IndexGPU::generate_index::copy_rest_to_separate_arrays"); - details::index_gpu::copy_rest_to_separate_arrays<<>>(generated_rest_d.data(), - read_ids_d_.data(), - positions_in_reads_d_.data(), - directions_of_reads_d_.data(), - representations_d_.size()); + details::index_gpu::copy_rest_to_separate_arrays<<>>(generated_rest_d.data(), + read_ids_d_.data(), + positions_in_reads_d_.data(), + directions_of_reads_d_.data(), + representations_d_.size()); } // now generate the index elements - details::index_gpu::find_first_occurrences_of_representations(allocator_, + details::index_gpu::find_first_occurrences_of_representations(allocator, unique_representations_d_, first_occurrence_of_representations_d_, representations_d_, - cuda_stream_); + cuda_stream); if (filtering_parameter < 1.0) { - details::index_gpu::filter_out_most_common_representations(allocator_, + details::index_gpu::filter_out_most_common_representations(allocator, filtering_parameter, representations_d_, read_ids_d_, @@ -865,7 +963,7 @@ void IndexGPU::generate_index(const io::FastaParser& parser, directions_of_reads_d_, unique_representations_d_, first_occurrence_of_representations_d_, - cuda_stream_); + cuda_stream); } } diff --git a/cudamapper/src/index_host_copy.cu b/cudamapper/src/index_host_copy.cu index b36e811dc..5a83e50dd 100644 --- a/cudamapper/src/index_host_copy.cu +++ b/cudamapper/src/index_host_copy.cu @@ -14,11 +14,12 @@ * limitations under the License. */ -#include #include "index_host_copy.cuh" #include "index_gpu.cuh" #include "minimizer.hpp" +#include + namespace claraparabricks { @@ -36,87 +37,132 @@ IndexHostCopy::IndexHostCopy(const Index& index, : first_read_id_(first_read_id) , kmer_size_(kmer_size) , window_size_(window_size) -{ - GW_NVTX_RANGE(profiler, "cache_index"); + , memory_pinner_(*this) + , cuda_stream_(cuda_stream) +{ + GW_NVTX_RANGE(profiler, "index_host_copy::constructor"); + + // Use only one large array to store all arrays in order to reduce fragmentation when using pool allocators + // Align all arrays according to the largest type + constexpr size_t alignment_bytes = std::max({alignof(representation_t), alignof(read_id_t), alignof(position_in_read_t), alignof(SketchElement::DirectionOfRepresentation), alignof(std::uint32_t)}); + + const std::size_t representations_bytes = claraparabricks::genomeworks::ceiling_divide(index.representations().size() * sizeof(representation_t), alignment_bytes) * alignment_bytes; + const std::size_t read_ids_bytes = claraparabricks::genomeworks::ceiling_divide(index.read_ids().size() * sizeof(read_id_t), alignment_bytes) * alignment_bytes; + const std::size_t positions_in_reads_bytes = claraparabricks::genomeworks::ceiling_divide(index.positions_in_reads().size() * sizeof(position_in_read_t), alignment_bytes) * alignment_bytes; + const std::size_t directions_of_reads_bytes = claraparabricks::genomeworks::ceiling_divide(index.directions_of_reads().size() * sizeof(SketchElement::DirectionOfRepresentation), alignment_bytes) * alignment_bytes; + const std::size_t unique_representations_bytes = claraparabricks::genomeworks::ceiling_divide(index.unique_representations().size() * sizeof(representation_t), alignment_bytes) * alignment_bytes; + const std::size_t first_occurrence_of_representations_bytes = claraparabricks::genomeworks::ceiling_divide(index.first_occurrence_of_representations().size() * sizeof(std::uint32_t), alignment_bytes) * alignment_bytes; + + const std::size_t total_bytes = representations_bytes + + read_ids_bytes + + positions_in_reads_bytes + + directions_of_reads_bytes + + unique_representations_bytes + + first_occurrence_of_representations_bytes; + + { + GW_NVTX_RANGE(profiler, "index_host_copy::constructor::allocate_host_memory"); + underlying_array_.resize(total_bytes); + } + + std::size_t current_byte = 0; + representations_ = {reinterpret_cast(underlying_array_.data() + current_byte), index.representations().size()}; + current_byte += representations_bytes; + read_ids_ = {reinterpret_cast(underlying_array_.data() + current_byte), index.read_ids().size()}; + current_byte += read_ids_bytes; + positions_in_reads_ = {reinterpret_cast(underlying_array_.data() + current_byte), index.positions_in_reads().size()}; + current_byte += positions_in_reads_bytes; + directions_of_reads_ = {reinterpret_cast(underlying_array_.data() + current_byte), index.directions_of_reads().size()}; + current_byte += directions_of_reads_bytes; + unique_representations_ = {reinterpret_cast(underlying_array_.data() + current_byte), index.unique_representations().size()}; + current_byte += unique_representations_bytes; + first_occurrence_of_representations_ = {reinterpret_cast(underlying_array_.data() + current_byte), index.first_occurrence_of_representations().size()}; + + // register pinned memory, memory gets unpinned in finish_copying() + memory_pinner_.register_pinned_memory(); - representations_.resize(index.representations().size()); cudautils::device_copy_n(index.representations().data(), index.representations().size(), - representations_.data(), - cuda_stream); + representations_.data, + cuda_stream_); - read_ids_.resize(index.read_ids().size()); cudautils::device_copy_n(index.read_ids().data(), index.read_ids().size(), - read_ids_.data(), - cuda_stream); + read_ids_.data, + cuda_stream_); - positions_in_reads_.resize(index.positions_in_reads().size()); cudautils::device_copy_n(index.positions_in_reads().data(), index.positions_in_reads().size(), - positions_in_reads_.data(), - cuda_stream); + positions_in_reads_.data, + cuda_stream_); - directions_of_reads_.resize(index.directions_of_reads().size()); cudautils::device_copy_n(index.directions_of_reads().data(), index.directions_of_reads().size(), - directions_of_reads_.data(), - cuda_stream); + directions_of_reads_.data, + cuda_stream_); - unique_representations_.resize(index.unique_representations().size()); cudautils::device_copy_n(index.unique_representations().data(), index.unique_representations().size(), - unique_representations_.data(), - cuda_stream); + unique_representations_.data, + cuda_stream_); - first_occurrence_of_representations_.resize(index.first_occurrence_of_representations().size()); cudautils::device_copy_n(index.first_occurrence_of_representations().data(), index.first_occurrence_of_representations().size(), - first_occurrence_of_representations_.data(), - cuda_stream); + first_occurrence_of_representations_.data, + cuda_stream_); number_of_reads_ = index.number_of_reads(); number_of_basepairs_in_longest_read_ = index.number_of_basepairs_in_longest_read(); - // This is not completely necessary, but if removed one has to make sure that the next step - // uses the same stream or that sync is done in caller - GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream)); + // no stream synchronization, synchronization done in finish_copying() +} + +void IndexHostCopy::finish_copying() const +{ + GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream_)); + memory_pinner_.unregister_pinned_memory(); } std::unique_ptr IndexHostCopy::copy_index_to_device(DefaultDeviceAllocator allocator, const cudaStream_t cuda_stream) const { + GW_NVTX_RANGE(profiler, "index_host_copy::copy_index_to_device"); + // register pinned memory, memory gets unpinned in finish_copying() + memory_pinner_.register_pinned_memory(); + return std::make_unique>(allocator, - *this, + this, cuda_stream); + + // no stream synchronization, synchronization done in finish_copying() } -const std::vector& IndexHostCopy::representations() const +const IndexHostCopyBase::Span IndexHostCopy::representations() const { return representations_; } -const std::vector& IndexHostCopy::read_ids() const +const IndexHostCopyBase::Span IndexHostCopy::read_ids() const { return read_ids_; } -const std::vector& IndexHostCopy::positions_in_reads() const +const IndexHostCopyBase::Span IndexHostCopy::positions_in_reads() const { return positions_in_reads_; } -const std::vector& IndexHostCopy::directions_of_reads() const +const IndexHostCopyBase::Span IndexHostCopy::directions_of_reads() const { return directions_of_reads_; } -const std::vector& IndexHostCopy::unique_representations() const +const IndexHostCopyBase::Span IndexHostCopy::unique_representations() const { return unique_representations_; } -const std::vector& IndexHostCopy::first_occurrence_of_representations() const +const IndexHostCopyBase::Span IndexHostCopy::first_occurrence_of_representations() const { return first_occurrence_of_representations_; } @@ -146,6 +192,48 @@ std::uint64_t IndexHostCopy::window_size() const return window_size_; } +IndexHostCopy::IndexHostMemoryPinner::IndexHostMemoryPinner(IndexHostCopy& index_host_copy) + : index_host_copy_(index_host_copy) + , times_memory_pinned_(0) +{ +} + +IndexHostCopy::IndexHostMemoryPinner::~IndexHostMemoryPinner() +{ + // if memory was not unregistered (due to either a bug or an expection) unregister it + if (times_memory_pinned_ != 0) + { + assert(!"memory should always be unregistered by unregister_pinned_memory()"); + GW_NVTX_RANGE(profiler, "index_host_memory_pinner::unregister_pinned_memory"); + GW_CU_CHECK_ERR(cudaHostUnregister(index_host_copy_.underlying_array_.data())); + } +} + +void IndexHostCopy::IndexHostMemoryPinner::register_pinned_memory() +{ + // only pin memory if it hasn't been pinned yet + if (0 == times_memory_pinned_) + { + GW_NVTX_RANGE(profiler, "index_host_memory_pinner::register_pinned_memory"); + GW_CU_CHECK_ERR(cudaHostRegister(index_host_copy_.underlying_array_.data(), + index_host_copy_.underlying_array_.size() * sizeof(gw_byte_t), + cudaHostRegisterDefault)); + } + ++times_memory_pinned_; +} + +void IndexHostCopy::IndexHostMemoryPinner::unregister_pinned_memory() +{ + assert(times_memory_pinned_ > 0); + // only unpin memory if this is the last unpinning + if (1 == times_memory_pinned_) + { + GW_NVTX_RANGE(profiler, "index_host_memory_pinner::unregister_pinned_memory"); + GW_CU_CHECK_ERR(cudaHostUnregister(index_host_copy_.underlying_array_.data())); + } + --times_memory_pinned_; +} + } // namespace cudamapper } // namespace genomeworks diff --git a/cudamapper/src/index_host_copy.cuh b/cudamapper/src/index_host_copy.cuh index a8d0908b6..17ed9918d 100644 --- a/cudamapper/src/index_host_copy.cuh +++ b/cudamapper/src/index_host_copy.cuh @@ -26,14 +26,15 @@ namespace genomeworks namespace cudamapper { + /// IndexHostCopy - Creates and maintains a copy of computed IndexGPU elements on the host /// /// class IndexHostCopy : public IndexHostCopyBase { public: - /// \brief Constructor - /// \brief cache the computed index to host + /// \brief Constructor - Starts creating a copy of index on the host + /// Copy is done asynchronously and one should wait for it to finish with finish_copying() /// \param index - pointer to computed index parameters (vectors of sketch elements) on GPU /// \param first_read_id - representing smallest read_id in index /// \param kmer_size - number of basepairs in a k-mer @@ -53,29 +54,32 @@ public: std::unique_ptr copy_index_to_device(DefaultDeviceAllocator allocator, const cudaStream_t cuda_stream = 0) const override; + /// \brief waits for copy to be done + void finish_copying() const override; + /// \brief returns an array of representations of sketch elements (stored on host) /// \return an array of representations of sketch elements - const std::vector& representations() const override; + const Span representations() const override; /// \brief returns an array of reads ids for sketch elements (stored on host) /// \return an array of reads ids for sketch elements - const std::vector& read_ids() const override; + const Span read_ids() const override; /// \brief returns an array of starting positions of sketch elements in their reads (stored on host) /// \return an array of starting positions of sketch elements in their reads - const std::vector& positions_in_reads() const override; + const Span positions_in_reads() const override; /// \brief returns an array of directions in which sketch elements were read (stored on host) /// \return an array of directions in which sketch elements were read - const std::vector& directions_of_reads() const override; + const Span directions_of_reads() const override; /// \brief returns an array where each representation is recorded only once, sorted by representation (stored on host) /// \return an array where each representation is recorded only once, sorted by representation - const std::vector& unique_representations() const override; + const Span unique_representations() const override; /// \brief returns first occurrence of corresponding representation from unique_representations(), plus one more element with the total number of sketch elements (stored on host) /// \return first occurrence of corresponding representation from unique_representations(), plus one more element with the total number of sketch elements - const std::vector& first_occurrence_of_representations() const override; + const Span first_occurrence_of_representations() const override; /// \brief returns number of reads in input data /// \return number of reads in input data @@ -98,13 +102,49 @@ public: std::uint64_t window_size() const override; private: - std::vector representations_; - std::vector read_ids_; - std::vector positions_in_reads_; - std::vector directions_of_reads_; - - std::vector unique_representations_; - std::vector first_occurrence_of_representations_; + /// IndexHostMemoryPinner - registers and unregisters host array in given IndexHostCopy as pinned memory + class IndexHostMemoryPinner + { + public: + /// \brief Constructor - registers pinned memory + /// \param index_host_copy - IndexHostCopy whose arrays should be registered + IndexHostMemoryPinner(IndexHostCopy& index_host_copy); + + IndexHostMemoryPinner(const IndexHostMemoryPinner&) = delete; + IndexHostMemoryPinner& operator=(const IndexHostMemoryPinner&) = delete; + IndexHostMemoryPinner(IndexHostMemoryPinner&&) = delete; + IndexHostMemoryPinner& operator=(IndexHostMemoryPinner&&) = delete; + + /// \brief Destructor - unregisters pinned memory if it hasn't been unregistered yet + ~IndexHostMemoryPinner(); + + /// \brief registers pinned memory + void register_pinned_memory(); + + /// \brief unregisteres pinned memory + void unregister_pinned_memory(); + + private: + IndexHostCopy& index_host_copy_; + // Theoretically speaking it could happen that the same IndexHostCopy gets copied multiple time in a row. In that case + // memory should be unpinned only once the last copy has finished (i.e. the caller waits for it to be finished). + // This counter is increased every time new copy have started and decreased every time the user waits for the copy to finish. + int32_t times_memory_pinned_; + }; + + // use a single underlying vector in order to reduce memory fragmentation when using pool allocators + std::vector underlying_array_; + + Span representations_; + Span read_ids_; + Span positions_in_reads_; + Span directions_of_reads_; + Span unique_representations_; + Span first_occurrence_of_representations_; + + mutable IndexHostMemoryPinner memory_pinner_; + + cudaStream_t cuda_stream_; read_id_t number_of_reads_; position_in_read_t number_of_basepairs_in_longest_read_; diff --git a/cudamapper/src/main.cu b/cudamapper/src/main.cu index e39447302..f01449ac4 100644 --- a/cudamapper/src/main.cu +++ b/cudamapper/src/main.cu @@ -195,14 +195,17 @@ struct OverlapsAndCigars }; /// \brief does overlapping and matching for pairs of query and target indices from device_batch -/// \param device_batch -/// \param device_cache data will be loaded into cache within the function +/// \param device_batch list of query and target indices to be processed +/// \param query_index_cache indices should be loaded into cache beforehand +/// \param target_index_cache indices should be loaded into cache beforehand /// \param application_parameters -/// \param overlaps_and_cigars_to_process overlaps and cigars are output here and the then consumed by another thread +/// \param device_allocator +/// \param overlaps_and_cigars_to_process overlaps and cigars are output here and then consumed by another thread /// \param number_of_skipped_pairs_of_indices number of pairs of indices skipped due to OOM error, variable shared between all threads, each call increases the number by the number of skipped pairs -/// \param cuda_stream +/// \param cuda_stream cuda stream on which the computation should be done void process_one_device_batch(const IndexBatch& device_batch, - IndexCacheDevice& device_cache, + std::shared_ptr query_index_cache, + std::shared_ptr target_index_cache, const ApplicationParameters& application_parameters, DefaultDeviceAllocator device_allocator, ThreadsafeProducerConsumer& overlaps_and_cigars_to_process, @@ -212,11 +215,7 @@ void process_one_device_batch(const IndexBatch& device_batch, GW_NVTX_RANGE(profiler, "main::process_one_device_batch"); const std::vector& query_index_descriptors = device_batch.query_indices; const std::vector& target_index_descriptors = device_batch.target_indices; - - // fetch indices for this batch from host memory assert(!query_index_descriptors.empty() && !target_index_descriptors.empty()); - device_cache.generate_query_cache_content(query_index_descriptors); - device_cache.generate_target_cache_content(target_index_descriptors); // process pairs of query and target indices for (const IndexDescriptor& query_index_descriptor : query_index_descriptors) @@ -226,8 +225,8 @@ void process_one_device_batch(const IndexBatch& device_batch, // if doing all-to-all skip pairs in which target batch has smaller id than query batch as it will be covered by symmetry if (!application_parameters.all_to_all || target_index_descriptor.first_read() >= query_index_descriptor.first_read()) { - std::shared_ptr query_index = device_cache.get_index_from_query_cache(query_index_descriptor); - std::shared_ptr target_index = device_cache.get_index_from_target_cache(target_index_descriptor); + std::shared_ptr query_index = query_index_cache->get_index(query_index_descriptor); + std::shared_ptr target_index = target_index_cache->get_index(target_index_descriptor); try { @@ -279,18 +278,16 @@ void process_one_device_batch(const IndexBatch& device_batch, } /// \brief loads one batch into host memory and then processes its device batches one by one -/// \param batch +/// \param batch list of all query and target indices that belong to this batch, as well as subgroups of those indices that belong to device batches /// \param application_parameters -/// \param host_cache data will be loaded into cache within the function -/// \param device_cache data will be loaded into cache within the function +/// \param host_index_cache data will be loaded into cache within the function /// \param overlaps_and_cigars_to_process overlaps and cigars are output to this structure and the then consumed by another thread /// \param number_of_skipped_pairs_of_indices number of pairs of indices skipped due to OOM error, variable shared between all threads, each call increases the number by the number of skipped pairs /// \param cuda_stream void process_one_batch(const BatchOfIndices& batch, const ApplicationParameters& application_parameters, DefaultDeviceAllocator device_allocator, - IndexCacheHost& host_cache, - IndexCacheDevice& device_cache, + HostIndexCache& host_index_cache, ThreadsafeProducerConsumer& overlaps_and_cigars_to_process, std::atomic& number_of_skipped_pairs_of_indices, cudaStream_t cuda_stream) @@ -306,27 +303,65 @@ void process_one_batch(const BatchOfIndices& batch, // load indices into host memory { + GW_NVTX_RANGE(profiler, "main::process_one_batch::generte_host_indices"); assert(!host_batch.query_indices.empty() && !host_batch.target_indices.empty() && !device_batches.empty()); - GW_NVTX_RANGE(profiler, "main::process_one_batch::host_indices"); - host_cache.generate_query_cache_content(host_batch.query_indices, - device_batches.front().query_indices, - skip_copy_to_host); - host_cache.generate_target_cache_content(host_batch.target_indices, - device_batches.front().target_indices, - skip_copy_to_host); + host_index_cache.generate_content(CacheType::query_cache, + host_batch.query_indices, + device_batches.front().query_indices, + skip_copy_to_host); + host_index_cache.generate_content(CacheType::target_cache, + host_batch.target_indices, + device_batches.front().target_indices, + skip_copy_to_host); } // process device batches one by one - for (const IndexBatch& device_batch : batch.device_batches) + // Processing one device batch is overlapped with fetching indices from host to device for the next device batch. + // Loop uses copy_device_batch_index as its index, compute_device_batch_index is equal to copy_device_batch_index - 1 + // (compute_device_batch_index does not actually exist). + // copy_device_batch_index loops over one more element because for such element compute_device_batch_index would have been equal to the last batch + std::shared_ptr query_cache_being_copied_into; + std::shared_ptr query_cache_with_ready_data; + std::shared_ptr target_cache_being_copied_into; + std::shared_ptr target_cache_with_ready_data; + for (int32_t copy_device_batch_index = 0; copy_device_batch_index < get_size(batch.device_batches) + 1; ++copy_device_batch_index) { - process_one_device_batch(device_batch, - device_cache, - application_parameters, - device_allocator, - overlaps_and_cigars_to_process, - number_of_skipped_pairs_of_indices, - cuda_stream); + if (copy_device_batch_index > 0) + { + // if not the first batch wait for previous batch to finish copying + GW_NVTX_RANGE(profiler, "main::process_one_batch::finish_generating_device_indices"); + query_cache_being_copied_into->wait_for_data_to_be_ready(); + target_cache_being_copied_into->wait_for_data_to_be_ready(); + query_cache_with_ready_data = query_cache_being_copied_into; + target_cache_with_ready_data = target_cache_being_copied_into; + } + + if (copy_device_batch_index < get_size(batch.device_batches)) + { + // if not pass-the-last batch start copying the batch + GW_NVTX_RANGE(profiler, "main::process_one_batch::start_generating_device_indices"); + query_cache_being_copied_into = host_index_cache.start_copying_indices_to_device(CacheType::query_cache, + batch.device_batches[copy_device_batch_index].query_indices); + target_cache_being_copied_into = host_index_cache.start_copying_indices_to_device(CacheType::target_cache, + batch.device_batches[copy_device_batch_index].target_indices); + } + + if (copy_device_batch_index > 0) + { + // when copy_device_batch_index == 0 then compute_device_batch_index == -1, so there is no batch to process + GW_NVTX_RANGE(profiler, "main::process_one_batch::process_device_batch"); + process_one_device_batch(batch.device_batches[copy_device_batch_index - 1], + query_cache_with_ready_data, + target_cache_with_ready_data, + application_parameters, + device_allocator, + overlaps_and_cigars_to_process, + number_of_skipped_pairs_of_indices, + cuda_stream); + } + + GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream)); } } @@ -370,15 +405,32 @@ void postprocess_and_write_thread_function(const int32_t device_id, 0.5); } - // write to output + // write to output PAF, SAM, or BAM format { - GW_NVTX_RANGE(profiler, "main::postprocess_and_write_thread::print_paf"); - print_paf(overlaps, - cigars, - *application_parameters.query_parser, - *application_parameters.target_parser, - application_parameters.kmer_size, - output_mutex); + GW_NVTX_RANGE(profiler, "main::postprocess_and_write_thread::print_function"); +#ifdef GW_BUILD_HTSLIB + if (application_parameters.format == OutputFormat::PAF) + { +#endif + print_paf(overlaps, + cigars, + *application_parameters.query_parser, + *application_parameters.target_parser, + application_parameters.kmer_size, + output_mutex); +#ifdef GW_BUILD_HTSLIB + } + // SAM or BAM, depends on type of format + else + { + print_sam(overlaps, + cigars, + *application_parameters.query_parser, + *application_parameters.target_parser, + application_parameters.format, + output_mutex); + } +#endif } } } @@ -393,7 +445,8 @@ void postprocess_and_write_thread_function(const int32_t device_id, /// \param batches_of_indices /// \param application_parameters /// \param output_mutex -/// \param cuda_stream +/// \param cuda_stream_computation +/// \param cuda_stream_copy /// \param number_of_total_batches /// \param number_of_skipped_pairs_of_indices /// \param number_of_processed_batches @@ -401,7 +454,8 @@ void worker_thread_function(const int32_t device_id, ThreadsafeDataProvider& batches_of_indices, const ApplicationParameters& application_parameters, std::mutex& output_mutex, - cudaStream_t cuda_stream, + cudaStream_t cuda_stream_computation, + cudaStream_t cuda_stream_copy, const int64_t number_of_total_batches, std::atomic& number_of_skipped_pairs_of_indices, std::atomic& number_of_processed_batches) @@ -411,22 +465,21 @@ void worker_thread_function(const int32_t device_id, // This function is expected to run in a separate thread so set current device in order to avoid problems GW_CU_CHECK_ERR(cudaSetDevice(device_id)); - DefaultDeviceAllocator device_allocator = create_default_device_allocator(application_parameters.max_cached_memory_bytes); - - // create host_cache, data is not loaded at this point but later as each batch gets processed - auto host_cache = std::make_shared(application_parameters.all_to_all, - device_allocator, - application_parameters.query_parser, - application_parameters.target_parser, - application_parameters.kmer_size, - application_parameters.windows_size, - true, // hash_representations - application_parameters.filtering_parameter, - cuda_stream); - - // create host_cache, data is not loaded at this point but later as each batch gets processed - IndexCacheDevice device_cache(application_parameters.all_to_all, - host_cache); + // Whenever device_allocator is used directly (e.g. in Thrust library) it will be associated with cuda_stream_computation + DefaultDeviceAllocator device_allocator = create_default_device_allocator(application_parameters.max_cached_memory_bytes, + cuda_stream_computation); + + // create index_cache, indices are not created at this point but later as each batch gets processed + HostIndexCache host_index_cache(application_parameters.all_to_all, + device_allocator, + application_parameters.query_parser, + application_parameters.target_parser, + application_parameters.kmer_size, + application_parameters.windows_size, + true, // hash_representations + application_parameters.filtering_parameter, + cuda_stream_computation, + cuda_stream_copy); // data structure used to exchange data with postprocess_and_write_thread ThreadsafeProducerConsumer overlaps_and_cigars_to_process; @@ -460,11 +513,10 @@ void worker_thread_function(const int32_t device_id, process_one_batch(batch_of_indices.value(), application_parameters, device_allocator, - *host_cache, - device_cache, + host_index_cache, overlaps_and_cigars_to_process, number_of_skipped_pairs_of_indices, - cuda_stream); + cuda_stream_computation); } // tell writer thread that there will be no more overlaps and it can finish once it has written all overlaps @@ -476,7 +528,7 @@ void worker_thread_function(const int32_t device_id, } // by this point all GPU work should anyway be done as postprocess_and_write_thread also finished and all GPU work had to be done before last values could be written - GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream)); + GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream_computation)); } } // namespace @@ -516,23 +568,26 @@ int main(int argc, char* argv[]) // pairs of indices might be skipped if they cause out of memory errors std::atomic number_of_skipped_pairs_of_indices{0}; + // explicitly assign one stream for computations and one for D2H and H2D copies of indices to each GPU + std::vector cuda_streams_computation; + std::vector cuda_streams_copy; + // create worker threads (one thread per device) // these thread process batches_of_indices one by one std::vector worker_threads; - // CudaStreams for each thread - std::vector cuda_streams; - for (int32_t device_id = 0; device_id < parameters.num_devices; ++device_id) { GW_CU_CHECK_ERR(cudaSetDevice(device_id)); - cuda_streams.emplace_back(make_cuda_stream()); + cuda_streams_computation.emplace_back(make_cuda_stream()); + cuda_streams_copy.emplace_back(make_cuda_stream()); worker_threads.emplace_back(worker_thread_function, device_id, std::ref(batches_of_indices), std::ref(parameters), std::ref(output_mutex), - cuda_streams.back().get(), + cuda_streams_computation.back().get(), + cuda_streams_copy.back().get(), number_of_total_batches, std::ref(number_of_skipped_pairs_of_indices), std::ref(number_of_processed_batches)); diff --git a/cudamapper/src/matcher_gpu.cu b/cudamapper/src/matcher_gpu.cu index 36a9ee173..eb93d62df 100644 --- a/cudamapper/src/matcher_gpu.cu +++ b/cudamapper/src/matcher_gpu.cu @@ -40,7 +40,7 @@ MatcherGPU::MatcherGPU(DefaultDeviceAllocator allocator, const Index& query_index, const Index& target_index, const cudaStream_t cuda_stream) - : anchors_d_(allocator) + : anchors_d_(0, allocator, cuda_stream) { GW_NVTX_RANGE(profile, "matcherGPU"); if (query_index.unique_representations().size() == 0 || target_index.unique_representations().size() == 0) diff --git a/cudamapper/src/overlapper.cpp b/cudamapper/src/overlapper.cpp index 1b6bd9341..b6632f52a 100644 --- a/cudamapper/src/overlapper.cpp +++ b/cudamapper/src/overlapper.cpp @@ -19,6 +19,7 @@ #include #include #include +#include #include "cudamapper_utils.hpp" #include "overlapper_triggered.hpp" @@ -134,13 +135,13 @@ namespace cudamapper void Overlapper::post_process_overlaps(std::vector& overlaps, const bool drop_fused_overlaps) { - const auto num_overlaps = get_size(overlaps); - bool in_fuse = false; - int fused_target_start; - int fused_query_start; - int fused_target_end; - int fused_query_end; - int num_residues = 0; + const auto num_overlaps = get_size(overlaps); + bool in_fuse = false; + position_in_read_t fused_target_start = std::numeric_limits::max(); + position_in_read_t fused_query_start = std::numeric_limits::max(); + position_in_read_t fused_target_end = std::numeric_limits::max(); + position_in_read_t fused_query_end = std::numeric_limits::max(); + int num_residues = 0; Overlap prev_overlap; std::vector drop_overlap_mask; if (drop_fused_overlaps) @@ -306,7 +307,6 @@ void Overlapper::rescue_overlap_ends(std::vector& overlaps, const std::int32_t extension, const float required_similarity) { - auto reverse_overlap = [](cudamapper::Overlap& overlap, std::uint32_t target_sequence_length) { overlap.relative_strand = overlap.relative_strand == RelativeStrand::Forward ? RelativeStrand::Reverse : RelativeStrand::Forward; position_in_read_t start_tmp = overlap.target_start_position_in_read_; @@ -350,7 +350,7 @@ void Overlapper::rescue_overlap_ends(std::vector& overlaps, while (rescue_rounds < max_rescue_rounds) { - details::overlapper::extend_overlap_by_sequence_similarity(overlap, query_view, target_view, 100, 0.9); + details::overlapper::extend_overlap_by_sequence_similarity(overlap, query_view, target_view, extension, required_similarity); ++rescue_rounds; if (overlap.query_end_position_in_read_ == prev_query_start && overlap.query_end_position_in_read_ == prev_query_end && diff --git a/cudamapper/src/utils.cpp b/cudamapper/src/utils.cpp index 1f4e040f3..52224f620 100644 --- a/cudamapper/src/utils.cpp +++ b/cudamapper/src/utils.cpp @@ -15,13 +15,20 @@ */ #include +#include +#include #include #include #include +#include #include +#ifdef GW_BUILD_HTSLIB +#include "kroundup.h" +#endif + namespace claraparabricks { @@ -115,6 +122,200 @@ void print_paf(const std::vector& overlaps, } } +#ifdef GW_BUILD_HTSLIB +namespace +{ + +static inline void encode_cigar(bam1_t* const alignment, const std::string& cigar) +{ + uint32_t* bam_cigar_start = bam_get_cigar(alignment); + memcpy(bam_cigar_start, cigar.c_str(), cigar.length()); + alignment->core.n_cigar = cigar.length(); + + return; +} + +static inline void encode_seq(bam1_t* const alignment, const std::string& seq) +{ + // This table was taken from bam_construct_seq() for base -> nibble encoding + static const char L[256] = + { + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 0, 15, 15, + 15, 1, 14, 2, 13, 15, 15, 4, 11, 15, 15, 12, 15, 3, 15, 15, + 15, 15, 5, 6, 8, 15, 7, 9, 15, 10, 15, 15, 15, 15, 15, 15, + 15, 1, 14, 2, 13, 15, 15, 4, 11, 15, 15, 12, 15, 3, 15, 15, + 15, 15, 5, 6, 8, 15, 7, 9, 15, 10, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, + 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15, 15}; + + const int32_t len = get_size(seq); + + // encode bases as nibbles and write them into the alignment struct 2 bases at a time + // 4 high bits are first base, 4 low bits are second base + uint8_t* bam_seq_start = bam_get_seq(alignment); + int32_t i = 0; + for (; (i + 1) < len; i += 2) + { + *bam_seq_start++ = (L[static_cast(seq[i])] << 4) + L[static_cast(seq[i + 1])]; + } + // odd number of bases, so we have one left over + if (i < len) + { + *bam_seq_start++ = L[static_cast(seq[i])] << 4; + } + + alignment->core.l_qseq = len; + + return; +} + +static inline void encode_qual(bam1_t* alignment) +{ + // if htslib encounters 0xff at the start of the QUAL section, it writes default value (*) + auto bam_qual_start = bam_get_qual(alignment); + *bam_qual_start = 0xff; +} + +} // namespace + +void print_sam(const std::vector& overlaps, + const std::vector& cigars, + const io::FastaParser& query_parser, + const io::FastaParser& target_parser, + const OutputFormat format, + std::mutex& write_output_mutex, + int argc, + char* argv[]) +{ + GW_NVTX_RANGE(profiler, "print_sam::formatting_output"); + + // Assume output is stdout, and assume SAM output by default + // Rest of the add()/write() functions choose based on samFile format + // use hts_close here directly, because sam_close is a macro for hts_close, which the compiler did not like + using samFilePtr_t = std::unique_ptr; + + auto file = (format == OutputFormat::SAM) ? samFilePtr_t(sam_open("-", "wh"), &hts_close) : samFilePtr_t(sam_open("-", "bwh"), &hts_close); + auto header = std::unique_ptr(sam_hdr_init(), &sam_hdr_destroy); + int result = 0; + + if (file == nullptr) + { + throw std::runtime_error("print_sam: cannot open file stream for writing"); + } + + const int64_t number_of_overlaps_to_print = get_size(overlaps); + for (int64_t i = 0; i < number_of_overlaps_to_print; ++i) + { + const std::string& target_read_name = target_parser.get_sequence_by_id(overlaps[i].target_read_id_).name; + const std::string length = std::to_string(target_parser.get_sequence_by_id(overlaps[i].target_read_id_).seq.length()); + + result = sam_hdr_add_line(header.get(), "SQ", "SN", target_read_name.c_str(), "LN", length.c_str(), + "CL", NULL); + if (result < 0) + { + std::cerr << "print_sam: could not add header value" << std::endl; + } + } + + // If we have the information to write out the CL section, do it + if ((argc != -1) && (argv != nullptr)) + { + auto command_line = std::unique_ptr(stringify_argv(argc, argv), &free); + result = sam_hdr_add_pg(header.get(), "cudamapper", "VN", claraparabricks_genomeworks_version().c_str(), + "CL", *command_line.get(), NULL); + } + else + { + result = sam_hdr_add_pg(header.get(), "cudamapper", "VN", claraparabricks_genomeworks_version().c_str(), NULL); + } + if (result < 0) + { + std::cerr << "print_sam: could not add PG header line" << std::endl; + } + + { + result = sam_hdr_write(file.get(), header.get()); + if (result < 0) + { + std::cerr << "print_sam: could not add PG header line" << std::endl; + } + } + + // write out mandatory fields for alignments + for (int64_t i = 0; i < number_of_overlaps_to_print; ++i) + { + const std::string& query_read_name = query_parser.get_sequence_by_id(overlaps[i].query_read_id_).name; + auto alignment = std::unique_ptr(bam_init1(), &bam_destroy1); + + // write QNAME field + bam_set_qname(alignment.get(), query_read_name.c_str()); + + // At this point we need to handle mem allocs ourselves, find necessary data size + size_t total_size = 0; + if (!cigars.empty()) + { + total_size = alignment->core.l_qname + alignment->core.l_extranul // len query name + how many padding '\0' chars + + cigars[i].length() + ((query_parser.get_sequence_by_id(overlaps[i].query_read_id_).seq.length() + 1) / 2); // sequence length and div by 2 because bases in the struct are encoded as nibbles + } + else + { + // case where we don't have CIGAR strings. See above calculation for details + total_size = alignment->core.l_qname + alignment->core.l_extranul + ((query_parser.get_sequence_by_id(overlaps[i].query_read_id_).seq.length() + 1) / 2); + } + const size_t max_data = kroundup64(total_size); + if (total_size >= alignment->m_data) + { + alignment->data = static_cast(realloc(alignment->data, max_data)); + } + alignment->l_data = total_size; + alignment->m_data = max_data; + + // write FLAG field + alignment->core.flag = 0; + + // write POS, MAPQ + // NOTE hardcode MAPQ to 255 like in print_paf, but SAM specification says we shouldn't do this + alignment->core.pos = static_cast(overlaps[i].query_start_position_in_read_); + alignment->core.qual = 255; + + // write CIGAR + if (!cigars.empty()) + { + encode_cigar(alignment.get(), cigars[i]); + } + + // write RNEXT, PNEXT, and TLEN + // all left as blank/default for now + + // write SEQ + encode_seq(alignment.get(), query_parser.get_sequence_by_id(overlaps[i].query_read_id_).seq); + + // QUAL is set to * by default + encode_qual(alignment.get()); + + // TODO: write AUX data if available + + std::lock_guard lg(write_output_mutex); + result = sam_write1(file.get(), header.get(), alignment.get()); + if (result < 0) + { + throw std::runtime_error("ERROR, print_sam: could not write alignment"); + } + } + + return; +} +#endif + std::vector group_reads_into_indices(const io::FastaParser& parser, const number_of_basepairs_t max_basepairs_per_index) { diff --git a/cudamapper/tests/Test_CudamapperIndexCache.cu b/cudamapper/tests/Test_CudamapperIndexCache.cu index a426c4477..8f0acfb95 100644 --- a/cudamapper/tests/Test_CudamapperIndexCache.cu +++ b/cudamapper/tests/Test_CudamapperIndexCache.cu @@ -36,9 +36,7 @@ namespace genomeworks namespace cudamapper { -// *** Test IndexCacheHost *** - -void check_if_index_is_correct(const std::shared_ptr& index, +void check_if_index_is_correct(const std::shared_ptr& index, const std::vector& expected_representations, const std::vector& expected_read_ids, const std::vector& expected_positions_in_reads, @@ -108,7 +106,7 @@ void check_if_index_is_correct(const std::shared_ptr& index, ASSERT_EQ(index_maximum_kmer_size, expected_maximum_kmer_size) << " test_uid: " << test_uid; } -TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) +TEST(TestCudamapperIndexCaching, test_index_cache_same_query_and_target) { // catcaag_aagcta.fasta k = 3 w = 2 @@ -164,7 +162,8 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) // CATCAAG_AAGCTA // All minimizers: AAG(4f0), AAG(0f1), AGC(2r1), ATC(1f0), ATG(0r0), CAA(3f0), CTA(3f1) - CudaStream cuda_stream = make_cuda_stream(); + CudaStream cuda_stream_generate = make_cuda_stream(); + CudaStream cuda_stream_copy = make_cuda_stream(); const bool same_query_and_target = true; std::shared_ptr query_parser = io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/catcaag_aagcta.fasta"); @@ -336,19 +335,24 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) std::vector catcaag_aagcta_separate_index_descriptors({catcaag_index_descriptor, aagcta_index_descriptor}); std::vector catcaag_aagcta_one_index_descriptors({catcaag_aagcta_index_descriptor}); - IndexCacheHost index_host_cache(same_query_and_target, - allocator, - query_parser, - target_parser, - k, - w, - hash_representations, - filtering_parameter, - cuda_stream.get()); + HostIndexCache host_cache(same_query_and_target, + allocator, + query_parser, + target_parser, + k, + w, + hash_representations, + filtering_parameter, + cuda_stream_generate.get(), + cuda_stream_copy.get()); + + host_cache.generate_content(CacheType::query_cache, + catcaag_index_descriptors); - index_host_cache.generate_query_cache_content(catcaag_index_descriptors); + std::shared_ptr device_cache_query = host_cache.start_copying_indices_to_device(CacheType::query_cache, catcaag_index_descriptors); + device_cache_query->wait_for_data_to_be_ready(); - auto index_query_catcaag = index_host_cache.get_index_from_query_cache(catcaag_index_descriptor); + auto index_query_catcaag = device_cache_query->get_index(catcaag_index_descriptor); check_if_index_is_correct(index_query_catcaag, catcaag_representations, catcaag_read_ids, @@ -361,17 +365,18 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_1"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(catcaag_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); - - index_host_cache.generate_target_cache_content(aagcta_index_descriptors); - - index_query_catcaag = index_host_cache.get_index_from_query_cache(catcaag_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_1"); + ASSERT_THROW(device_cache_query->get_index(aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(host_cache.start_copying_indices_to_device(CacheType::target_cache, aagcta_index_descriptors), IndexNotFoundException); + ASSERT_THROW(host_cache.start_copying_indices_to_device(CacheType::target_cache, aagcta_index_descriptors), IndexNotFoundException); + + host_cache.generate_content(CacheType::target_cache, aagcta_index_descriptors); + std::shared_ptr device_cache_target = host_cache.start_copying_indices_to_device(CacheType::target_cache, aagcta_index_descriptors); + device_cache_target->wait_for_data_to_be_ready(); + + index_query_catcaag = device_cache_query->get_index(catcaag_index_descriptor); check_if_index_is_correct(index_query_catcaag, catcaag_representations, catcaag_read_ids, @@ -384,12 +389,12 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_2"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(catcaag_index_descriptor)); - auto index_target_aagcta = index_host_cache.get_index_from_target_cache(aagcta_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_2"); + ASSERT_THROW(device_cache_query->get_index(aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(device_cache_target->get_index(catcaag_index_descriptor), IndexNotFoundException); + auto index_target_aagcta = device_cache_target->get_index(aagcta_index_descriptor); check_if_index_is_correct(index_target_aagcta, aagcta_representations, aagcta_read_ids, @@ -402,14 +407,17 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_3"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_3"); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); - index_host_cache.generate_query_cache_content(aagcta_index_descriptors); + device_cache_query = nullptr; + host_cache.generate_content(CacheType::query_cache, aagcta_index_descriptors); + device_cache_query = host_cache.start_copying_indices_to_device(CacheType::query_cache, aagcta_index_descriptors); + device_cache_query->wait_for_data_to_be_ready(); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_index_descriptor)); - auto index_query_aagcta = index_host_cache.get_index_from_query_cache(aagcta_index_descriptor); + ASSERT_THROW(device_cache_query->get_index(catcaag_index_descriptor), IndexNotFoundException); + auto index_query_aagcta = device_cache_query->get_index(aagcta_index_descriptor); check_if_index_is_correct(index_query_aagcta, aagcta_representations, aagcta_read_ids, @@ -422,11 +430,11 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_4"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(catcaag_index_descriptor)); - index_target_aagcta = index_host_cache.get_index_from_target_cache(aagcta_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_4"); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(device_cache_target->get_index(catcaag_index_descriptor), IndexNotFoundException); + index_target_aagcta = device_cache_target->get_index(aagcta_index_descriptor); check_if_index_is_correct(index_target_aagcta, aagcta_representations, aagcta_read_ids, @@ -439,13 +447,16 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_5"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_5"); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); - index_host_cache.generate_query_cache_content(catcaag_aagcta_separate_index_descriptors); + device_cache_query = nullptr; + host_cache.generate_content(CacheType::query_cache, catcaag_aagcta_separate_index_descriptors); + device_cache_query = host_cache.start_copying_indices_to_device(CacheType::query_cache, catcaag_aagcta_separate_index_descriptors); + device_cache_query->wait_for_data_to_be_ready(); - auto index_query_catcaag_separate = index_host_cache.get_index_from_query_cache(catcaag_index_descriptor); + auto index_query_catcaag_separate = device_cache_query->get_index(catcaag_index_descriptor); check_if_index_is_correct(index_query_catcaag_separate, catcaag_representations, catcaag_read_ids, @@ -458,9 +469,9 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_6"); - auto index_query_aagcta_separate = index_host_cache.get_index_from_query_cache(aagcta_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_6"); + auto index_query_aagcta_separate = device_cache_query->get_index(aagcta_index_descriptor); check_if_index_is_correct(index_query_aagcta_separate, aagcta_representations, aagcta_read_ids, @@ -473,11 +484,11 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_7"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(catcaag_index_descriptor)); - index_target_aagcta = index_host_cache.get_index_from_target_cache(aagcta_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_7"); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(device_cache_target->get_index(catcaag_index_descriptor), IndexNotFoundException); + index_target_aagcta = device_cache_target->get_index(aagcta_index_descriptor); check_if_index_is_correct(index_target_aagcta, aagcta_representations, aagcta_read_ids, @@ -490,13 +501,16 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_8"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_8"); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); - index_host_cache.generate_target_cache_content(catcaag_aagcta_one_index_descriptors); + device_cache_target = nullptr; + host_cache.generate_content(CacheType::target_cache, catcaag_aagcta_one_index_descriptors); + device_cache_target = host_cache.start_copying_indices_to_device(CacheType::target_cache, catcaag_aagcta_one_index_descriptors); + device_cache_target->wait_for_data_to_be_ready(); - index_query_catcaag_separate = index_host_cache.get_index_from_query_cache(catcaag_index_descriptor); + index_query_catcaag_separate = device_cache_query->get_index(catcaag_index_descriptor); check_if_index_is_correct(index_query_catcaag_separate, catcaag_representations, catcaag_read_ids, @@ -509,9 +523,9 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_9"); - index_query_aagcta_separate = index_host_cache.get_index_from_query_cache(aagcta_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_9"); + index_query_aagcta_separate = device_cache_query->get_index(aagcta_index_descriptor); check_if_index_is_correct(index_query_aagcta_separate, aagcta_representations, aagcta_read_ids, @@ -524,12 +538,12 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_10"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_query_cache(catcaag_aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(catcaag_index_descriptor)); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(aagcta_index_descriptor)); - auto catcaag_aagcta_target_aagcta = index_host_cache.get_index_from_target_cache(catcaag_aagcta_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_10"); + ASSERT_THROW(device_cache_query->get_index(catcaag_aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(device_cache_target->get_index(catcaag_index_descriptor), IndexNotFoundException); + ASSERT_THROW(device_cache_target->get_index(aagcta_index_descriptor), IndexNotFoundException); + auto catcaag_aagcta_target_aagcta = device_cache_target->get_index(catcaag_aagcta_index_descriptor); check_if_index_is_correct(catcaag_aagcta_target_aagcta, catcaag_aagcta_representations, catcaag_aagcta_read_ids, @@ -542,11 +556,11 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_same_query_and_target) catcaag_aagcta_largest_read_id, catcaag_aagcta_number_of_basepairs_in_longest_read, catcaag_aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_same_query_and_target_11"); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_11"); } -TEST(TestCudamapperIndexCaching, test_index_cache_host_not_the_same_query_and_target) +TEST(TestCudamapperIndexCaching, test_index_cache_not_the_same_query_and_target) { // aagcta.fasta ctacaag.fasta k = 3 w = 2 @@ -594,7 +608,8 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_not_the_same_query_and_ta // All minimizers: AAG(4f), ATC(1f), ATG(0r), CAA(3f) - CudaStream cuda_stream = make_cuda_stream(); + CudaStream cuda_stream_generate = make_cuda_stream(); + CudaStream cuda_stream_copy = make_cuda_stream(); const bool same_query_and_target = false; std::shared_ptr query_parser = io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/aagcta.fasta"); @@ -696,19 +711,22 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_not_the_same_query_and_ta IndexDescriptor index_descriptor(0, 1); std::vector index_descriptors({index_descriptor}); - IndexCacheHost index_host_cache(same_query_and_target, - allocator, - query_parser, - target_parser, - k, - w, - hash_representations, - filtering_parameter, - cuda_stream.get()); - - index_host_cache.generate_query_cache_content(index_descriptors); - - auto index_query_aagcta = index_host_cache.get_index_from_query_cache(index_descriptor); + HostIndexCache host_cache(same_query_and_target, + allocator, + query_parser, + target_parser, + k, + w, + hash_representations, + filtering_parameter, + cuda_stream_generate.get(), + cuda_stream_copy.get()); + + host_cache.generate_content(CacheType::query_cache, index_descriptors); + std::shared_ptr device_cache_query = host_cache.start_copying_indices_to_device(CacheType::query_cache, index_descriptors); + device_cache_query->wait_for_data_to_be_ready(); + + auto index_query_aagcta = device_cache_query->get_index(index_descriptor); check_if_index_is_correct(index_query_aagcta, aagcta_representations, aagcta_read_ids, @@ -721,13 +739,15 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_not_the_same_query_and_ta aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_not_the_same_query_and_target_1"); - ASSERT_ANY_THROW(index_host_cache.get_index_from_target_cache(index_descriptor)); + cuda_stream_generate.get(), + "test_index_cache_not_the_same_query_and_target_1"); + ASSERT_THROW(host_cache.start_copying_indices_to_device(CacheType::target_cache, index_descriptors), IndexNotFoundException); - index_host_cache.generate_target_cache_content(index_descriptors); + host_cache.generate_content(CacheType::target_cache, index_descriptors); + std::shared_ptr device_cache_target = host_cache.start_copying_indices_to_device(CacheType::target_cache, index_descriptors); + device_cache_target->wait_for_data_to_be_ready(); - index_query_aagcta = index_host_cache.get_index_from_query_cache(index_descriptor); + index_query_aagcta = device_cache_query->get_index(index_descriptor); check_if_index_is_correct(index_query_aagcta, aagcta_representations, aagcta_read_ids, @@ -740,9 +760,9 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_not_the_same_query_and_ta aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_not_the_same_query_and_target_2"); - auto index_target_catcaag = index_host_cache.get_index_from_target_cache(index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_not_the_same_query_and_target_2"); + auto index_target_catcaag = device_cache_target->get_index(index_descriptor); check_if_index_is_correct(index_target_catcaag, catcaag_representations, catcaag_read_ids, @@ -755,15 +775,16 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_not_the_same_query_and_ta catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_not_the_same_query_and_target_3"); + cuda_stream_generate.get(), + "test_index_cache_not_the_same_query_and_target_3"); } -TEST(TestCudamapperIndexCaching, test_index_cache_host_keep_on_device) +TEST(TestCudamapperIndexCaching, test_index_cache_keep_on_device) { // AAGCTA: AAG(0f), AGC(2r), CTA(3f) - CudaStream cuda_stream = make_cuda_stream(); + CudaStream cuda_stream_generate = make_cuda_stream(); + CudaStream cuda_stream_copy = make_cuda_stream(); const bool same_query_and_target = true; std::shared_ptr query_parser = io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/aagcta.fasta"); @@ -819,29 +840,34 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_keep_on_device) IndexDescriptor index_descriptor(0, 1); std::vector index_descriptors({index_descriptor}); - auto index_cache_host = std::make_shared(same_query_and_target, - allocator, - query_parser, - target_parser, - k, - w, - hash_representations, - filtering_parameter, - cuda_stream.get()); - - index_cache_host->generate_query_cache_content(index_descriptors, - index_descriptors); - index_cache_host->generate_target_cache_content(index_descriptors, - index_descriptors); - - auto index_query_temp_device_cache = index_cache_host->get_index_from_query_cache(index_descriptor); - auto index_query_copy_from_host = index_cache_host->get_index_from_query_cache(index_descriptor); - auto index_target_temp_device_cache = index_cache_host->get_index_from_target_cache(index_descriptor); - auto index_target_copy_from_host = index_cache_host->get_index_from_target_cache(index_descriptor); - - ASSERT_EQ(index_query_temp_device_cache, index_target_temp_device_cache); - ASSERT_NE(index_query_temp_device_cache, index_query_copy_from_host); - ASSERT_NE(index_target_temp_device_cache, index_target_copy_from_host); + HostIndexCache host_cache(same_query_and_target, + allocator, + query_parser, + target_parser, + k, + w, + hash_representations, + filtering_parameter, + cuda_stream_generate.get(), + cuda_stream_copy.get()); + + host_cache.generate_content(CacheType::query_cache, index_descriptors, index_descriptors); + std::shared_ptr device_cache_query_1 = host_cache.start_copying_indices_to_device(CacheType::query_cache, index_descriptors); // 1st copy, kept on device + host_cache.generate_content(CacheType::target_cache, index_descriptors, index_descriptors); + std::shared_ptr device_cache_target_1 = host_cache.start_copying_indices_to_device(CacheType::target_cache, index_descriptors); + device_cache_query_1->wait_for_data_to_be_ready(); + device_cache_target_1->wait_for_data_to_be_ready(); + + auto index_query_temp_device_cache = device_cache_query_1->get_index(index_descriptor); + auto index_target_temp_device_cache = device_cache_target_1->get_index(index_descriptor); + + std::shared_ptr device_cache_query_2 = host_cache.start_copying_indices_to_device(CacheType::query_cache, index_descriptors); + std::shared_ptr device_cache_target_2 = host_cache.start_copying_indices_to_device(CacheType::target_cache, index_descriptors); + device_cache_query_2->wait_for_data_to_be_ready(); + device_cache_target_2->wait_for_data_to_be_ready(); + + auto index_query_copy_from_host = device_cache_query_2->get_index(index_descriptor); // 2nd copy, copied from host + auto index_target_copy_from_host = device_cache_target_2->get_index(index_descriptor); check_if_index_is_correct(index_query_temp_device_cache, aagcta_representations, @@ -855,8 +881,8 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_keep_on_device) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_keep_on_device_1"); + cuda_stream_generate.get(), + "test_index_cache_keep_on_device_1"); check_if_index_is_correct(index_query_copy_from_host, aagcta_representations, aagcta_read_ids, @@ -869,8 +895,8 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_keep_on_device) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_keep_on_device_2"); + cuda_stream_generate.get(), + "test_index_cache_keep_on_device_2"); check_if_index_is_correct(index_target_temp_device_cache, aagcta_representations, aagcta_read_ids, @@ -883,8 +909,8 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_keep_on_device) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_keep_on_device_3"); + cuda_stream_generate.get(), + "test_index_cache_keep_on_device_3"); check_if_index_is_correct(index_target_copy_from_host, aagcta_representations, aagcta_read_ids, @@ -897,13 +923,11 @@ TEST(TestCudamapperIndexCaching, test_index_cache_host_keep_on_device) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_host_keep_on_device_4"); + cuda_stream_generate.get(), + "test_index_cache_keep_on_device_4"); } -// *** Test IndexCacheDevice *** - -TEST(TestCudamapperIndexCaching, test_index_cache_device_same_query_and_target) +TEST(TestCudamapperIndexCaching, test_index_cache_same_query_and_target_2) { // >read_0 // CATCAAG @@ -913,7 +937,8 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_same_query_and_target) // CATCAAG minimizers: AAG(4f), ATC(1f), ATG(0r), CAA(3f) // AAGCTA minimizers: AAG(0f), AGC(2r), CTA(3f) - CudaStream cuda_stream = make_cuda_stream(); + CudaStream cuda_stream_generate = make_cuda_stream(); + CudaStream cuda_stream_copy = make_cuda_stream(); const bool same_query_and_target = true; std::shared_ptr query_parser = io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/catcaag_aagcta.fasta"); @@ -1017,23 +1042,21 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_same_query_and_target) std::vector aagcta_index_descriptors({aagcta_index_descriptor}); std::vector catcaag_aagcta_index_descriptors({catcaag_index_descriptor, aagcta_index_descriptor}); - auto index_cache_host = std::make_shared(same_query_and_target, - allocator, - query_parser, - target_parser, - k, - w, - hash_representations, - filtering_parameter, - cuda_stream.get()); - - IndexCacheDevice index_cache_device(same_query_and_target, - index_cache_host); - - index_cache_host->generate_query_cache_content(catcaag_index_descriptors); - ASSERT_ANY_THROW(index_cache_device.get_index_from_query_cache(catcaag_index_descriptor)); - index_cache_device.generate_query_cache_content(catcaag_index_descriptors); - auto index_query_catcaag = index_cache_device.get_index_from_query_cache(catcaag_index_descriptor); + HostIndexCache host_cache(same_query_and_target, + allocator, + query_parser, + target_parser, + k, + w, + hash_representations, + filtering_parameter, + cuda_stream_generate.get(), + cuda_stream_copy.get()); + + host_cache.generate_content(CacheType::query_cache, catcaag_index_descriptors); + std::shared_ptr device_cache_query = host_cache.start_copying_indices_to_device(CacheType::query_cache, catcaag_index_descriptors); + device_cache_query->wait_for_data_to_be_ready(); + auto index_query_catcaag = device_cache_query->get_index(catcaag_index_descriptor); check_if_index_is_correct(index_query_catcaag, catcaag_representations, catcaag_read_ids, @@ -1046,18 +1069,16 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_same_query_and_target) catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_device_same_query_and_target_1"); - ASSERT_ANY_THROW(index_cache_device.get_index_from_query_cache(aagcta_index_descriptor)); - ASSERT_ANY_THROW(index_cache_device.get_index_from_target_cache(catcaag_index_descriptor)); - ASSERT_ANY_THROW(index_cache_device.get_index_from_target_cache(aagcta_index_descriptor)); - - index_cache_host->generate_target_cache_content(catcaag_aagcta_index_descriptors); - ASSERT_ANY_THROW(index_cache_device.get_index_from_target_cache(catcaag_index_descriptor)); - ASSERT_ANY_THROW(index_cache_device.get_index_from_target_cache(aagcta_index_descriptor)); - index_cache_device.generate_target_cache_content(catcaag_aagcta_index_descriptors); - - auto index_target_catcaag = index_cache_device.get_index_from_target_cache(catcaag_index_descriptor); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_2_1"); + ASSERT_THROW(device_cache_query->get_index(aagcta_index_descriptor), IndexNotFoundException); + ASSERT_THROW(host_cache.start_copying_indices_to_device(CacheType::target_cache, catcaag_aagcta_index_descriptors), IndexNotFoundException); + + host_cache.generate_content(CacheType::target_cache, catcaag_aagcta_index_descriptors); + std::shared_ptr device_cache_target = host_cache.start_copying_indices_to_device(CacheType::target_cache, catcaag_aagcta_index_descriptors); + device_cache_target->wait_for_data_to_be_ready(); + + auto index_target_catcaag = device_cache_target->get_index(catcaag_index_descriptor); ASSERT_EQ(index_query_catcaag, index_target_catcaag); // check same object is used because same_query_and_target == true check_if_index_is_correct(index_target_catcaag, catcaag_representations, @@ -1071,10 +1092,10 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_same_query_and_target) catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_device_same_query_and_target_2"); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_2_2"); - auto index_target_aagcta = index_cache_device.get_index_from_target_cache(aagcta_index_descriptor); + auto index_target_aagcta = device_cache_target->get_index(aagcta_index_descriptor); check_if_index_is_correct(index_target_aagcta, aagcta_representations, aagcta_read_ids, @@ -1087,22 +1108,23 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_same_query_and_target) aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_device_same_query_and_target_3"); + cuda_stream_generate.get(), + "test_index_cache_same_query_and_target_2_3"); // get the same query and target indices again and make sure they point to the same objects as the last time - auto index_query_catcaag_1 = index_cache_device.get_index_from_query_cache(catcaag_index_descriptor); - auto index_target_aagcta_1 = index_cache_device.get_index_from_target_cache(aagcta_index_descriptor); + auto index_query_catcaag_1 = device_cache_query->get_index(catcaag_index_descriptor); + auto index_target_aagcta_1 = device_cache_target->get_index(aagcta_index_descriptor); ASSERT_EQ(index_query_catcaag, index_query_catcaag_1); ASSERT_EQ(index_target_aagcta, index_target_aagcta_1); } -TEST(TestCudamapperIndexCaching, test_index_cache_device_not_the_same_query_and_target) +TEST(TestCudamapperIndexCaching, test_index_cache_not_the_same_query_and_target_2) { // AAGCTA: AAG(0f), AGC(2r), CTA(3f) // CATCAAG: AAG(4f), ATC(1f), ATG(0r), CAA(3f) - CudaStream cuda_stream = make_cuda_stream(); + CudaStream cuda_stream_generate = make_cuda_stream(); + CudaStream cuda_stream_copy = make_cuda_stream(); const bool same_query_and_target = false; std::shared_ptr query_parser = io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/aagcta.fasta"); @@ -1204,25 +1226,22 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_not_the_same_query_and_ IndexDescriptor index_descriptor(0, 1); std::vector index_descriptors({index_descriptor}); - auto index_cache_host = std::make_shared(same_query_and_target, - allocator, - query_parser, - target_parser, - k, - w, - hash_representations, - filtering_parameter, - cuda_stream.get()); - - IndexCacheDevice index_cache_device(same_query_and_target, - index_cache_host); - - index_cache_host->generate_query_cache_content(index_descriptors); - ASSERT_ANY_THROW(index_cache_device.get_index_from_query_cache(index_descriptor)); - ASSERT_ANY_THROW(index_cache_device.get_index_from_target_cache(index_descriptor)); - - index_cache_device.generate_query_cache_content(index_descriptors); - auto index_query = index_cache_device.get_index_from_query_cache(index_descriptor); + HostIndexCache host_cache(same_query_and_target, + allocator, + query_parser, + target_parser, + k, + w, + hash_representations, + filtering_parameter, + cuda_stream_generate.get(), + cuda_stream_copy.get()); + + host_cache.generate_content(CacheType::query_cache, index_descriptors); + ASSERT_THROW(host_cache.start_copying_indices_to_device(CacheType::target_cache, index_descriptors), IndexNotFoundException); + std::shared_ptr device_cache_query = host_cache.start_copying_indices_to_device(CacheType::query_cache, index_descriptors); + device_cache_query->wait_for_data_to_be_ready(); + auto index_query = device_cache_query->get_index(index_descriptor); check_if_index_is_correct(index_query, aagcta_representations, aagcta_read_ids, @@ -1235,17 +1254,16 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_not_the_same_query_and_ aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_device_not_the_same_query_and_target_1"); - ASSERT_ANY_THROW(index_cache_device.get_index_from_target_cache(index_descriptor)); - - ASSERT_ANY_THROW(index_cache_device.generate_target_cache_content(index_descriptors)); + cuda_stream_generate.get(), + "test_index_cache_not_the_same_query_and_target_2_1"); + ASSERT_THROW(host_cache.start_copying_indices_to_device(CacheType::target_cache, index_descriptors), IndexNotFoundException); - index_cache_host->generate_target_cache_content(index_descriptors); - index_cache_device.generate_target_cache_content(index_descriptors); + host_cache.generate_content(CacheType::target_cache, index_descriptors); + std::shared_ptr device_cache_target = host_cache.start_copying_indices_to_device(CacheType::target_cache, index_descriptors); + device_cache_target->wait_for_data_to_be_ready(); - index_query = index_cache_device.get_index_from_query_cache(index_descriptor); - auto index_target = index_cache_device.get_index_from_target_cache(index_descriptor); + index_query = device_cache_query->get_index(index_descriptor); + auto index_target = device_cache_target->get_index(index_descriptor); ASSERT_NE(index_query, index_target); check_if_index_is_correct(index_query, aagcta_representations, @@ -1259,8 +1277,8 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_not_the_same_query_and_ aagcta_largest_read_id, aagcta_number_of_basepairs_in_longest_read, aagcta_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_device_not_the_same_query_and_target_2"); + cuda_stream_generate.get(), + "test_index_cache_not_the_same_query_and_target_2_2"); check_if_index_is_correct(index_target, catcaag_representations, catcaag_read_ids, @@ -1273,12 +1291,12 @@ TEST(TestCudamapperIndexCaching, test_index_cache_device_not_the_same_query_and_ catcaag_largest_read_id, catcaag_number_of_basepairs_in_longest_read, catcaag_maximum_kmer_size, - cuda_stream.get(), - "test_index_cache_device_not_the_same_query_and_target_3"); + cuda_stream_generate.get(), + "test_index_cache_not_the_same_query_and_target_2_3"); // get the same query and target indices again and make sure they point to the same objects as the last time - auto index_query_1 = index_cache_device.get_index_from_query_cache(index_descriptor); - auto index_target_1 = index_cache_device.get_index_from_target_cache(index_descriptor); + auto index_query_1 = device_cache_query->get_index(index_descriptor); + auto index_target_1 = device_cache_target->get_index(index_descriptor); ASSERT_EQ(index_query, index_query_1); ASSERT_EQ(index_target, index_target_1); } diff --git a/cudamapper/tests/Test_CudamapperIndexGPU.cu b/cudamapper/tests/Test_CudamapperIndexGPU.cu index 4b27afb3e..9350fcba8 100644 --- a/cudamapper/tests/Test_CudamapperIndexGPU.cu +++ b/cudamapper/tests/Test_CudamapperIndexGPU.cu @@ -1334,16 +1334,18 @@ void test_function(const std::string& filename, CudaStream cuda_stream = make_cuda_stream(); + // IndexDescriptors take the first_read and num_reads, get num_reads from past_the_last_read_id + IndexDescriptor descriptor = {first_read_id, (past_the_last_read_id - first_read_id)}; + IndexGPU index(allocator, *parser, - first_read_id, - past_the_last_read_id, + descriptor, kmer_size, window_size, false, filtering_parameter, cuda_stream.get()); - GW_CU_CHECK_ERR(cudaStreamSynchronize(cuda_stream.get())); + index.wait_to_be_ready(); ASSERT_EQ(index.number_of_reads(), expected_number_of_reads); if (0 == expected_number_of_reads) diff --git a/cudamapper/tests/Test_CudamapperMatcherGPU.cu b/cudamapper/tests/Test_CudamapperMatcherGPU.cu index ffe6165e9..58aa7e042 100644 --- a/cudamapper/tests/Test_CudamapperMatcherGPU.cu +++ b/cudamapper/tests/Test_CudamapperMatcherGPU.cu @@ -639,8 +639,10 @@ TEST(TestCudamapperMatcherGPU, OneReadOneMinimizer) { DefaultDeviceAllocator allocator = create_default_device_allocator(); std::unique_ptr parser = io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/gatt.fasta"); - std::unique_ptr query_index = Index::create_index(allocator, *parser, 0, parser->get_num_seqences(), 4, 1); - std::unique_ptr target_index = Index::create_index(allocator, *parser, 0, parser->get_num_seqences(), 4, 1); + std::unique_ptr query_index = Index::create_index_async(allocator, *parser, IndexDescriptor(0, parser->get_num_seqences()), 4, 1); + query_index->wait_to_be_ready(); + std::unique_ptr target_index = Index::create_index_async(allocator, *parser, IndexDescriptor(0, parser->get_num_seqences()), 4, 1); + target_index->wait_to_be_ready(); MatcherGPU matcher(allocator, *query_index, *target_index); thrust::host_vector anchors(matcher.anchors().size()); @@ -652,8 +654,10 @@ TEST(TestCudamapperMatcherGPU, AtLeastOneIndexEmpty) { DefaultDeviceAllocator allocator = create_default_device_allocator(); std::unique_ptr parser = io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/gatt.fasta"); - std::unique_ptr index_full = Index::create_index(allocator, *parser, 0, parser->get_num_seqences(), 4, 1); - std::unique_ptr index_empty = Index::create_index(allocator, *parser, 0, parser->get_num_seqences(), 5, 1); // kmer longer than read + std::unique_ptr index_full = Index::create_index_async(allocator, *parser, IndexDescriptor(0, parser->get_num_seqences()), 4, 1); + index_full->wait_to_be_ready(); + std::unique_ptr index_empty = Index::create_index_async(allocator, *parser, IndexDescriptor(0, parser->get_num_seqences()), 5, 1); // kmer longer than read + index_empty->wait_to_be_ready(); { MatcherGPU matcher(allocator, *index_full, *index_empty); diff --git a/cudamapper/tests/Test_CudamapperOverlapperTriggered.cu b/cudamapper/tests/Test_CudamapperOverlapperTriggered.cu index 9d8510415..cab478b2e 100644 --- a/cudamapper/tests/Test_CudamapperOverlapperTriggered.cu +++ b/cudamapper/tests/Test_CudamapperOverlapperTriggered.cu @@ -306,7 +306,7 @@ TEST(TestCudamapperOverlapperTriggerred, ReverseStrand) TEST(TestCudamapperOverlapperTriggerred, OverlapPostProcessingTwoForwardOverlapsTwoFusable) { - DefaultDeviceAllocator allocator; + DefaultDeviceAllocator allocator = create_default_device_allocator(); OverlapperTriggered overlapper(allocator); std::vector overlaps; @@ -359,7 +359,7 @@ TEST(TestCudamapperOverlapperTriggerred, OverlapPostProcessingTwoForwardOverlaps TEST(TestCudamapperOverlapperTriggerred, OverlapPostProcessingTwoForwardOverlapsOneFusable) { - DefaultDeviceAllocator allocator; + DefaultDeviceAllocator allocator = create_default_device_allocator(); OverlapperTriggered overlapper(allocator); std::vector overlaps; @@ -412,7 +412,7 @@ TEST(TestCudamapperOverlapperTriggerred, OverlapPostProcessingTwoForwardOverlaps TEST(TestCudamapperOverlapperTriggerred, OverlapPostProcessingOneForwardOneReverseBothFuasble) { - DefaultDeviceAllocator allocator; + DefaultDeviceAllocator allocator = create_default_device_allocator(); OverlapperTriggered overlapper(allocator); std::vector overlaps; diff --git a/cudamapper/tests/mock_index.cuh b/cudamapper/tests/mock_index.cuh index da89eb782..4515b3a0d 100644 --- a/cudamapper/tests/mock_index.cuh +++ b/cudamapper/tests/mock_index.cuh @@ -39,8 +39,7 @@ public: MockIndex(DefaultDeviceAllocator allocator) : IndexGPU(allocator, *genomeworks::io::create_kseq_fasta_parser(std::string(CUDAMAPPER_BENCHMARK_DATA_DIR) + "/gatt.fasta"), - 0, - 0, + IndexDescriptor(0, 0), 0, 0, true) diff --git a/cudapoa/CMakeLists.txt b/cudapoa/CMakeLists.txt index 53505f523..df600b0ec 100644 --- a/cudapoa/CMakeLists.txt +++ b/cudapoa/CMakeLists.txt @@ -38,7 +38,7 @@ endif() # Project specific NVCC flags, --expt-relaxed-constexpr is being added to allow using numeric_limits inside device kernels. # Using in CUDA 10.1+ to avoid compilation issues with CUDA <= 10.0. -set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} -std=c++14") +set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} -std=c++14 -arch=compute_60") if(gw_cuda_after_10_0) set(CUDA_NVCC_FLAGS "${CUDA_NVCC_FLAGS} --expt-relaxed-constexpr") endif() @@ -74,6 +74,7 @@ target_include_directories(${MODULE_NAME} ) add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/include) +add_doxygen_source_dir(${CMAKE_CURRENT_SOURCE_DIR}/README.md) add_executable(${MODULE_NAME}-bin src/main.cpp diff --git a/cudapoa/README.md b/cudapoa/README.md new file mode 100644 index 000000000..7b42694eb --- /dev/null +++ b/cudapoa/README.md @@ -0,0 +1,24 @@ +# CUDAPOA + +The `cudapoa` package provides a GPU-accelerated implementation of the [Partial Order Alignment](https://simpsonlab.github.io/2015/05/01/understanding-poa/) +algorithm. It is heavily influenced by [SPOA](https://github.com/rvaser/spoa) and in many cases can be considered a GPU-accelerated replacement. + +## Library +Built as `libcudapoa.[so|a]` + +* Generation of consensus sequences +* Generation of multi-sequence alignments (MSAs) +* Custom adaptive band implementation of POA +* Support for long and short read sequences + +APIs documented in [include](include/claraparabricks/genomeworks/cudapoa) folder. + +## Sample +[sample_cudapoa](samples/sample_cudapoa.cpp) - A prototypical binary to showcase the use of `libcudapoa` APIs. + +## Tool + +A command line tool for generating consensus and MSA from a list of `fasta`/`fastq` files. The tool +is built on top of `libcudapoa` and showcases optimization strategies for writing high performance +applications with `libcudapoa`. + diff --git a/cudapoa/benchmarks/multi_batch.hpp b/cudapoa/benchmarks/multi_batch.hpp index a88c0d30d..96e257f73 100644 --- a/cudapoa/benchmarks/multi_batch.hpp +++ b/cudapoa/benchmarks/multi_batch.hpp @@ -51,11 +51,12 @@ class MultiBatch size_t total = 0, free = 0; cudaSetDevice(0); cudaMemGetInfo(&free, &total); - size_t mem_per_batch = 0.9 * free / num_batches_; + DefaultDeviceAllocator allocator = create_default_device_allocator(0.9 * free); + int64_t mem_per_batch = 0.9 * free / num_batches_; for (int32_t batch = 0; batch < num_batches_; batch++) { streams_.emplace_back(make_cuda_stream()); - batches_.emplace_back(create_batch(0, streams_.back().get(), mem_per_batch, + batches_.emplace_back(create_batch(0, streams_.back().get(), allocator, mem_per_batch, OutputType::consensus, batch_size, -8, -6, 8)); diff --git a/cudapoa/include/claraparabricks/genomeworks/cudapoa/batch.hpp b/cudapoa/include/claraparabricks/genomeworks/cudapoa/batch.hpp index 3b8b416a2..664a0c451 100644 --- a/cudapoa/include/claraparabricks/genomeworks/cudapoa/batch.hpp +++ b/cudapoa/include/claraparabricks/genomeworks/cudapoa/batch.hpp @@ -21,6 +21,7 @@ #include #include #include +#include #include #include @@ -64,8 +65,6 @@ struct BatchConfig int32_t max_consensus_size; /// Maximum number of nodes in a POA graph, one graph per window int32_t max_nodes_per_graph; - /// Maximum vertical dimension of scoring matrix, which stores POA graph - int32_t matrix_graph_dimension; /// Maximum horizontal dimension of scoring matrix, which stores part of sequences used in scores matrix computation int32_t matrix_sequence_dimension; /// Band-width used in banded alignment, it also defines minimum band-width in adaptive alignment @@ -74,13 +73,16 @@ struct BatchConfig int32_t max_sequences_per_poa; /// Banding mode: full, static, adaptive BandMode band_mode; + /// Maximum distance of predecessor node used in NW computations for static or adaptive-banded + int32_t max_banded_pred_distance; /// constructor- set upper limit parameters based on max_seq_sz and band_width - BatchConfig(int32_t max_seq_sz = 1024, int32_t max_seq_per_poa = 100, int32_t band_width = 256, BandMode banding = BandMode::full_band, float adapive_storage_factor = 2.0); + BatchConfig(int32_t max_seq_sz = 1024, int32_t max_seq_per_poa = 100, int32_t band_width = 256, BandMode banding = BandMode::full_band, + float adapive_storage_factor = 2.0, float graph_length_factor = 3.0, int32_t max_pred_dist = 0); /// constructor- set all parameters separately - BatchConfig(int32_t max_seq_sz, int32_t max_consensus_sz, int32_t max_nodes_per_w, - int32_t band_width, int32_t max_seq_per_poa, int32_t matrix_seq_dim, BandMode banding); + BatchConfig(int32_t max_seq_sz, int32_t max_consensus_sz, int32_t max_nodes_per_poa, int32_t band_width, + int32_t max_seq_per_poa, int32_t matrix_seq_dim, BandMode banding, int32_t max_pred_dist); }; /// \class Batch @@ -163,17 +165,38 @@ class Batch /// /// \param device_id GPU device on which to run CUDA POA algorithm /// \param stream CUDA stream to use on GPU +/// \param allocator Allocator to use for internal device memory allocations /// \param max_gpu_mem Maximum GPU memory to use for this batch. /// \param output_mask which outputs to produce from POA (msa, consensus) /// \param batch_size defines upper limits for size of a POA batch, i.e. sequence length and other related parameters /// \param gap_score score to be assigned to a gap /// \param mismatch_score score to be assigned to a mismatch /// \param match_score score to be assigned for a match +/// \return Returns a unique pointer to a new Batch object +std::unique_ptr create_batch(int32_t device_id, + cudaStream_t stream, + DefaultDeviceAllocator allocator, + int64_t max_gpu_mem, + int8_t output_mask, + const BatchConfig& batch_size, + int16_t gap_score, + int16_t mismatch_score, + int16_t match_score); + +/// \brief Creates a new CUDA Batch object. /// +/// \param device_id GPU device on which to run CUDA POA algorithm +/// \param stream CUDA stream to use on GPU +/// \param max_gpu_mem Maximum GPU memory to use for this batch. +/// \param output_mask which outputs to produce from POA (msa, consensus) +/// \param batch_size defines upper limits for size of a POA batch, i.e. sequence length and other related parameters +/// \param gap_score score to be assigned to a gap +/// \param mismatch_score score to be assigned to a mismatch +/// \param match_score score to be assigned for a match /// \return Returns a unique pointer to a new Batch object std::unique_ptr create_batch(int32_t device_id, cudaStream_t stream, - size_t max_gpu_mem, + int64_t max_gpu_mem, int8_t output_mask, const BatchConfig& batch_size, int16_t gap_score, diff --git a/cudapoa/include/claraparabricks/genomeworks/cudapoa/cudapoa.hpp b/cudapoa/include/claraparabricks/genomeworks/cudapoa/cudapoa.hpp index 655859bb5..24f632c5c 100644 --- a/cudapoa/include/claraparabricks/genomeworks/cudapoa/cudapoa.hpp +++ b/cudapoa/include/claraparabricks/genomeworks/cudapoa/cudapoa.hpp @@ -16,6 +16,8 @@ #pragma once +#include + namespace claraparabricks { @@ -38,22 +40,36 @@ enum StatusType node_count_exceeded_maximum_graph_size, edge_count_exceeded_maximum_graph_size, exceeded_adaptive_banded_matrix_size, - seq_len_exceeded_maximum_nodes_per_window, + exceeded_maximum_predecessor_distance, loop_count_exceeded_upper_bound, output_type_unavailable, generic_error }; -/// Banding mode used in Needleman-Wunch algorithm -/// full_band performs computations on full scores matrix, highest accuracy -/// static_band performs computations on a fixed band along scores matrix diagonal, fastest implementation -/// adaptive_band, similar to static_band performs computations on a band along diagonal, but the band-width -/// can vary per alignment's score matrix, faster than full_band and more accurate than static_band +/// Generate corresponding error message for a given error type +/// \param [in] error_type input error code +/// \param [out] error_message corresponding error message +/// \param [out] error_hint possible hint to resolve the error +void decode_error(StatusType error_type, std::string& error_message, std::string& error_hint); + +/// Banding mode used in Needleman-Wunsch algorithm +/// - full_band performs computations on full scores matrix, highest accuracy +/// - static_band performs computations on a fixed band along scores matrix diagonal, fastest implementation +/// - adaptive_band, similar to static_band performs computations on a band along diagonal, but the band-width +/// can vary per alignment's score matrix, faster than full_band and more accurate than static_band +/// - static_band_traceback is similar to static_band, but uses traceback matrix. In this mode, score matrix is only +/// partially stored. The height of score matrix is equivalent to maximum predecessors distance and this maximum +/// distance is limited and smaller than full POA graph length, this can be a source of difference vs static_band. +/// Traceback matrix requires less memory compared to score matrix, and this banding mode can be useful for +/// long-read cases where GPU memory is limiting the parallelism. +/// - adaptive_band_traceback, similar to static_band_traceback but with varying band-width size enum BandMode { full_band = 0, static_band, - adaptive_band + adaptive_band, + static_band_traceback, + adaptive_band_traceback }; /// Initialize CUDA POA context. diff --git a/cudapoa/include/claraparabricks/genomeworks/cudapoa/utils.hpp b/cudapoa/include/claraparabricks/genomeworks/cudapoa/utils.hpp index 9ed9b49c4..ac23d22a2 100644 --- a/cudapoa/include/claraparabricks/genomeworks/cudapoa/utils.hpp +++ b/cudapoa/include/claraparabricks/genomeworks/cudapoa/utils.hpp @@ -59,6 +59,8 @@ void get_multi_batch_sizes(std::vector& list_of_batch_sizes, int32_t band_width = 256, BandMode band_mode = BandMode::adaptive_band, float adaptive_storage_factor = 2.0f, + float graph_length_factor = 3.0f, + int32_t max_pred_distance = 0, std::vector* bins_capacity = nullptr, float gpu_memory_usage_quota = 0.9, int32_t mismatch_score = -6, diff --git a/cudapoa/samples/sample_cudapoa.cpp b/cudapoa/samples/sample_cudapoa.cpp index b58be0187..773e8ee17 100644 --- a/cudapoa/samples/sample_cudapoa.cpp +++ b/cudapoa/samples/sample_cudapoa.cpp @@ -25,6 +25,7 @@ #include #include #include +#include using namespace claraparabricks::genomeworks; using namespace claraparabricks::genomeworks::cudapoa; @@ -46,7 +47,7 @@ std::unique_ptr initialize_batch(bool msa, const BatchConfig& batch_size) // Initialize CUDAPOA batch object for batched processing of POAs on the GPU. const int32_t device_id = 0; cudaStream_t stream = 0; - size_t mem_per_batch = 0.9 * free; // Using 90% of GPU available memory for CUDAPOA batch. + int64_t mem_per_batch = 0.9 * free; // Using 90% of GPU available memory for CUDAPOA batch. const int32_t mismatch_score = -6, gap_score = -8, match_score = 8; std::unique_ptr batch = create_batch(device_id, stream, @@ -63,6 +64,7 @@ std::unique_ptr initialize_batch(bool msa, const BatchConfig& batch_size) void process_batch(Batch* batch, bool msa_flag, bool print, std::vector& list_of_group_ids, int id_offset) { batch->generate_poa(); + std::string error_message, error_hint; StatusType status = StatusType::success; if (msa_flag) @@ -74,14 +76,20 @@ void process_batch(Batch* batch, bool msa_flag, bool print, std::vector status = batch->get_msa(msa, output_status); if (status != StatusType::success) { - std::cerr << "Could not generate MSA for batch : " << status << std::endl; + decode_error(status, error_message, error_hint); + std::cerr << "Could not generate MSA for batch : " << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } for (int32_t g = 0; g < get_size(msa); g++) { if (output_status[g] != StatusType::success) { - std::cerr << "Error generating MSA for POA group " << list_of_group_ids[g + id_offset] << ". Error type " << output_status[g] << std::endl; + decode_error(output_status[g], error_message, error_hint); + std::cerr << "Error generating MSA for POA group " << list_of_group_ids[g + id_offset] << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } else { @@ -105,14 +113,20 @@ void process_batch(Batch* batch, bool msa_flag, bool print, std::vector status = batch->get_consensus(consensus, coverage, output_status); if (status != StatusType::success) { - std::cerr << "Could not generate consensus for batch : " << status << std::endl; + decode_error(status, error_message, error_hint); + std::cerr << "Could not generate consensus for batch : " << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } for (int32_t g = 0; g < get_size(consensus); g++) { if (output_status[g] != StatusType::success) { - std::cerr << "Error generating consensus for POA group " << list_of_group_ids[g + id_offset] << ". Error type " << output_status[g] << std::endl; + decode_error(output_status[g], error_message, error_hint); + std::cerr << "Error generating consensus for POA group " << list_of_group_ids[g + id_offset] << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } else { @@ -131,7 +145,7 @@ int main(int argc, char** argv) int c = 0; bool msa = false; bool long_read = false; - BandMode band_mode = BandMode::adaptive_band; // 0: full, 1: static-band, 2: adaptive-band + BandMode band_mode = BandMode::adaptive_band; // 0: full, 1: static-band, 2: adaptive-band, 3- static-band-traceback 4- adaptive-band-traceback bool help = false; bool print = false; bool print_graph = false; @@ -148,9 +162,9 @@ int main(int argc, char** argv) long_read = true; break; case 'b': - if (std::stoi(optarg) < 0 || std::stoi(optarg) > 2) + if (std::stoi(optarg) < 0 || std::stoi(optarg) > 4) { - throw std::runtime_error("band-mode must be either 0 for full bands, 1 for static bands or 2 for adaptive bands"); + throw std::runtime_error("band-mode must be either 0 for full bands, 1 for static bands, 2 for adaptive bands, 3 and 4 for static and adaptive bands with traceback"); } band_mode = static_cast(std::stoi(optarg)); break; @@ -212,6 +226,9 @@ int main(int argc, char** argv) } } + // for error code message + std::string error_message, error_hint; + // analyze the POA groups and create a minimal set of batches to process them all std::vector list_of_batch_sizes; std::vector> list_of_groups_per_batch; @@ -303,7 +320,10 @@ int main(int argc, char** argv) if (status != StatusType::exceeded_maximum_poas && status != StatusType::success) { - std::cout << "Could not add POA group " << batch_group_ids[i] << " to batch " << b << ". Error code " << status << std::endl; + decode_error(status, error_message, error_hint); + std::cerr << "Could not add POA group " << batch_group_ids[i] << " to batch " << b << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; i++; } } diff --git a/cudapoa/src/allocate_block.hpp b/cudapoa/src/allocate_block.hpp index 0da1ae6c2..2b5771021 100644 --- a/cudapoa/src/allocate_block.hpp +++ b/cudapoa/src/allocate_block.hpp @@ -30,6 +30,7 @@ #include #include #include +#include #ifndef GW_LOG_LEVEL #ifndef NDEBUG @@ -50,37 +51,52 @@ namespace genomeworks namespace cudapoa { -template +template class BatchBlock { public: - BatchBlock(int32_t device_id, size_t avail_mem, int8_t output_mask, const BatchConfig& batch_size) + BatchBlock(int32_t device_id, DefaultDeviceAllocator allocator, int64_t max_mem, int8_t output_mask, const BatchConfig& batch_size) : max_sequences_per_poa_(throw_on_negative(batch_size.max_sequences_per_poa, "Maximum sequences per POA has to be non-negative")) , device_id_(throw_on_negative(device_id, "Device ID has to be non-negative")) , output_mask_(output_mask) { scoped_device_switch dev(device_id_); max_nodes_per_window_ = batch_size.max_nodes_per_graph; + traceback_alignment_ = batch_size.band_mode == BandMode::static_band_traceback || batch_size.band_mode == BandMode::adaptive_band_traceback; + score_matrix_height_ = traceback_alignment_ ? batch_size.max_banded_pred_distance : batch_size.max_nodes_per_graph; + score_matrix_width_ = batch_size.matrix_sequence_dimension; // calculate static and dynamic sizes of buffers needed per POA entry. int64_t host_size_fixed, device_size_fixed; int64_t host_size_per_poa, device_size_per_poa; std::tie(host_size_fixed, device_size_fixed, host_size_per_poa, device_size_per_poa) = calculate_space_per_poa(batch_size); - // Check minimum requirement for device memory - size_t minimum_device_mem = device_size_fixed + device_size_per_poa; + // Max memory that can be used = min(available free mem, upper limit on memory use) + int64_t avail_mem = std::min(get_size_of_largest_free_memory_block(allocator), max_mem); + int64_t minimum_device_mem = device_size_fixed + device_size_per_poa; if (avail_mem < minimum_device_mem) { - std::string msg = std::string("Require at least ") + std::string msg = std::string("Requires at least ") .append(std::to_string(minimum_device_mem)) .append(" bytes of device memory per CUDAPOA batch to process correctly."); throw std::runtime_error(msg); } - // Calculate max POAs possible based on available memory. - int64_t device_size_per_score_matrix = static_cast(batch_size.matrix_sequence_dimension) * - static_cast(batch_size.matrix_graph_dimension) * sizeof(ScoreT); - max_poas_ = avail_mem / (device_size_per_poa + device_size_per_score_matrix); + // compute device memory used for matrix buffer + // in banded traceback alignment, this is for traceback matrix, otherwise it is for score matrix + int64_t device_size_per_matrix = static_cast(batch_size.matrix_sequence_dimension) * + static_cast(batch_size.max_nodes_per_graph); + if (traceback_alignment_) + { + device_size_per_matrix *= sizeof(TraceT); + } + else + { + device_size_per_matrix *= sizeof(ScoreT); + } + + // Calculate max POAs possible based on available memory + max_poas_ = avail_mem / (device_size_per_poa + device_size_per_matrix); // Update final sizes for block based on calculated maximum POAs. output_size_ = max_poas_ * static_cast(batch_size.max_consensus_size); @@ -90,12 +106,11 @@ class BatchBlock // Allocate. GW_CU_CHECK_ERR(cudaHostAlloc((void**)&block_data_h_, total_h_, cudaHostAllocDefault)); - GW_CU_CHECK_ERR(cudaMalloc((void**)&block_data_d_, total_d_)); + block_data_d_ = device_buffer(total_d_, allocator); } ~BatchBlock() { - GW_CU_CHECK_ERR(cudaFree(block_data_d_)); GW_CU_CHECK_ERR(cudaFreeHost(block_data_h_)); } @@ -103,6 +118,7 @@ class BatchBlock { OutputDetails* output_details_h{}; OutputDetails* output_details_d{}; + uint8_t* block_data_d = block_data_d_.data(); // on host output_details_h = reinterpret_cast(&block_data_h_[offset_h_]); @@ -124,16 +140,16 @@ class BatchBlock offset_h_ += sizeof(OutputDetails); // on device - output_details_d->consensus = &block_data_d_[offset_d_]; + output_details_d->consensus = &block_data_d[offset_d_]; offset_d_ += cudautils::align(output_size_ * sizeof(*output_details_d->consensus)); if (output_mask_ & OutputType::consensus) { - output_details_d->coverage = reinterpret_castcoverage)>(&block_data_d_[offset_d_]); + output_details_d->coverage = reinterpret_castcoverage)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(output_size_ * sizeof(*output_details_d->coverage)); } if (output_mask_ & OutputType::msa) { - output_details_d->multiple_sequence_alignments = reinterpret_castmultiple_sequence_alignments)>(&block_data_d_[offset_d_]); + output_details_d->multiple_sequence_alignments = reinterpret_castmultiple_sequence_alignments)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(output_size_ * max_sequences_per_poa_ * sizeof(*output_details_d->multiple_sequence_alignments)); } @@ -146,6 +162,7 @@ class BatchBlock // on host InputDetails* input_details_h{}; InputDetails* input_details_d{}; + uint8_t* block_data_d = block_data_d_.data(); input_details_h = reinterpret_cast*>(&block_data_h_[offset_h_]); offset_h_ += sizeof(InputDetails); @@ -167,17 +184,17 @@ class BatchBlock offset_h_ += sizeof(InputDetails); // on device - input_details_d->sequences = &block_data_d_[offset_d_]; + input_details_d->sequences = &block_data_d[offset_d_]; offset_d_ += cudautils::align(input_size_ * sizeof(*input_details_d->sequences)); - input_details_d->base_weights = reinterpret_castbase_weights)>(&block_data_d_[offset_d_]); + input_details_d->base_weights = reinterpret_castbase_weights)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(input_size_ * sizeof(*input_details_d->base_weights)); - input_details_d->sequence_lengths = reinterpret_castsequence_lengths)>(&block_data_d_[offset_d_]); + input_details_d->sequence_lengths = reinterpret_castsequence_lengths)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(max_poas_ * max_sequences_per_poa_ * sizeof(*input_details_d->sequence_lengths)); - input_details_d->window_details = reinterpret_castwindow_details)>(&block_data_d_[offset_d_]); + input_details_d->window_details = reinterpret_castwindow_details)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(max_poas_ * sizeof(*input_details_d->window_details)); if (output_mask_ & OutputType::msa) { - input_details_d->sequence_begin_nodes_ids = reinterpret_castsequence_begin_nodes_ids)>(&block_data_d_[offset_d_]); + input_details_d->sequence_begin_nodes_ids = reinterpret_castsequence_begin_nodes_ids)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(max_poas_ * max_sequences_per_poa_ * sizeof(*input_details_d->sequence_begin_nodes_ids)); } @@ -185,42 +202,60 @@ class BatchBlock *input_details_d_p = input_details_d; } - void get_alignment_details(AlignmentDetails** alignment_details_d_p) + void get_alignment_details(AlignmentDetails** alignment_details_d_p) { - AlignmentDetails* alignment_details_d{}; - + AlignmentDetails* alignment_details_d{}; + uint8_t* block_data_d = block_data_d_.data(); // on host - alignment_details_d = reinterpret_cast*>(&block_data_h_[offset_h_]); - offset_h_ += sizeof(AlignmentDetails); + alignment_details_d = reinterpret_cast*>(&block_data_h_[offset_h_]); + offset_h_ += sizeof(AlignmentDetails); // on device; - alignment_details_d->alignment_graph = reinterpret_castalignment_graph)>(&block_data_d_[offset_d_]); + alignment_details_d->alignment_graph = reinterpret_castalignment_graph)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*alignment_details_d->alignment_graph) * max_nodes_per_window_ * max_poas_); - alignment_details_d->alignment_read = reinterpret_castalignment_read)>(&block_data_d_[offset_d_]); + alignment_details_d->alignment_read = reinterpret_castalignment_read)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*alignment_details_d->alignment_read) * max_nodes_per_window_ * max_poas_); + // in traceback banded mode, we store only part of scores matrix for forward computation in NW + if (traceback_alignment_) + { + alignment_details_d->scores = reinterpret_castscores)>(&block_data_d[offset_d_]); + offset_d_ += cudautils::align(sizeof(*alignment_details_d->scores) * score_matrix_width_ * score_matrix_height_ * max_poas_); + } + if (variable_bands_) { - alignment_details_d->band_starts = reinterpret_castband_starts)>(&block_data_d_[offset_d_]); + alignment_details_d->band_starts = reinterpret_castband_starts)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*alignment_details_d->band_starts) * max_nodes_per_window_ * max_poas_); - alignment_details_d->band_widths = reinterpret_castband_widths)>(&block_data_d_[offset_d_]); + alignment_details_d->band_widths = reinterpret_castband_widths)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*alignment_details_d->band_widths) * max_nodes_per_window_ * max_poas_); - alignment_details_d->band_head_indices = reinterpret_castband_head_indices)>(&block_data_d_[offset_d_]); + alignment_details_d->band_head_indices = reinterpret_castband_head_indices)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*alignment_details_d->band_head_indices) * max_nodes_per_window_ * max_poas_); - alignment_details_d->band_max_indices = reinterpret_castband_max_indices)>(&block_data_d_[offset_d_]); + alignment_details_d->band_max_indices = reinterpret_castband_max_indices)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*alignment_details_d->band_max_indices) * max_nodes_per_window_ * max_poas_); } - // rest of the available memory is assigned to scores buffer - alignment_details_d->scorebuf_alloc_size = total_d_ - offset_d_; - alignment_details_d->scores = reinterpret_castscores)>(&block_data_d_[offset_d_]); - *alignment_details_d_p = alignment_details_d; + if (!traceback_alignment_) + { + // in non-traceback alignments, where only scores buffer is used and traceback buffer size is 0, rest of the available memory is assigned to scores buffer + alignment_details_d->scorebuf_alloc_size = total_d_ - offset_d_; + alignment_details_d->scores = reinterpret_castscores)>(&block_data_d[offset_d_]); + alignment_details_d->traceback = nullptr; + } + else + { + // in traceback alignment, rest of the available memory is assigned to traceback buffer + alignment_details_d->scorebuf_alloc_size = total_d_ - offset_d_; + alignment_details_d->traceback = reinterpret_casttraceback)>(&block_data_d[offset_d_]); + } + + *alignment_details_d_p = alignment_details_d; } void get_graph_details(GraphDetails** graph_details_d_p, GraphDetails** graph_details_h_p) { GraphDetails* graph_details_d{}; GraphDetails* graph_details_h{}; - + uint8_t* block_data_d = block_data_d_.data(); // on host graph_details_h = reinterpret_cast*>(&block_data_h_[offset_h_]); offset_h_ += sizeof(GraphDetails); @@ -237,51 +272,51 @@ class BatchBlock graph_details_d->nodes = &block_data_h_[offset_h_]; // on device - graph_details_d->nodes = &block_data_d_[offset_d_]; + graph_details_d->nodes = &block_data_d[offset_d_]; offset_d_ += cudautils::align(sizeof(*graph_details_d->nodes) * max_nodes_per_window_ * max_poas_); - graph_details_d->node_alignments = reinterpret_castnode_alignments)>(&block_data_d_[offset_d_]); + graph_details_d->node_alignments = reinterpret_castnode_alignments)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->node_alignments) * max_nodes_per_window_ * CUDAPOA_MAX_NODE_ALIGNMENTS * max_poas_); - graph_details_d->node_alignment_count = reinterpret_castnode_alignment_count)>(&block_data_d_[offset_d_]); + graph_details_d->node_alignment_count = reinterpret_castnode_alignment_count)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->node_alignment_count) * max_nodes_per_window_ * max_poas_); - graph_details_d->incoming_edges = reinterpret_castincoming_edges)>(&block_data_d_[offset_d_]); + graph_details_d->incoming_edges = reinterpret_castincoming_edges)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->incoming_edges) * max_nodes_per_window_ * CUDAPOA_MAX_NODE_EDGES * max_poas_); - graph_details_d->incoming_edge_count = reinterpret_castincoming_edge_count)>(&block_data_d_[offset_d_]); + graph_details_d->incoming_edge_count = reinterpret_castincoming_edge_count)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->incoming_edge_count) * max_nodes_per_window_ * max_poas_); - graph_details_d->outgoing_edges = reinterpret_castoutgoing_edges)>(&block_data_d_[offset_d_]); + graph_details_d->outgoing_edges = reinterpret_castoutgoing_edges)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->outgoing_edges) * max_nodes_per_window_ * CUDAPOA_MAX_NODE_EDGES * max_poas_); - graph_details_d->outgoing_edge_count = reinterpret_castoutgoing_edge_count)>(&block_data_d_[offset_d_]); + graph_details_d->outgoing_edge_count = reinterpret_castoutgoing_edge_count)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->outgoing_edge_count) * max_nodes_per_window_ * max_poas_); - graph_details_d->incoming_edge_weights = reinterpret_castincoming_edge_weights)>(&block_data_d_[offset_d_]); + graph_details_d->incoming_edge_weights = reinterpret_castincoming_edge_weights)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->incoming_edge_weights) * max_nodes_per_window_ * CUDAPOA_MAX_NODE_EDGES * max_poas_); - graph_details_d->sorted_poa = reinterpret_castsorted_poa)>(&block_data_d_[offset_d_]); + graph_details_d->sorted_poa = reinterpret_castsorted_poa)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->sorted_poa) * max_nodes_per_window_ * max_poas_); - graph_details_d->sorted_poa_node_map = reinterpret_castsorted_poa_node_map)>(&block_data_d_[offset_d_]); + graph_details_d->sorted_poa_node_map = reinterpret_castsorted_poa_node_map)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->sorted_poa_node_map) * max_nodes_per_window_ * max_poas_); - graph_details_d->sorted_poa_local_edge_count = reinterpret_castsorted_poa_local_edge_count)>(&block_data_d_[offset_d_]); + graph_details_d->sorted_poa_local_edge_count = reinterpret_castsorted_poa_local_edge_count)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->sorted_poa_local_edge_count) * max_nodes_per_window_ * max_poas_); if (output_mask_ & OutputType::consensus) { - graph_details_d->consensus_scores = reinterpret_castconsensus_scores)>(&block_data_d_[offset_d_]); + graph_details_d->consensus_scores = reinterpret_castconsensus_scores)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->consensus_scores) * max_nodes_per_window_ * max_poas_); - graph_details_d->consensus_predecessors = reinterpret_castconsensus_predecessors)>(&block_data_d_[offset_d_]); + graph_details_d->consensus_predecessors = reinterpret_castconsensus_predecessors)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->consensus_predecessors) * max_nodes_per_window_ * max_poas_); } - graph_details_d->node_marks = reinterpret_castnode_marks)>(&block_data_d_[offset_d_]); + graph_details_d->node_marks = reinterpret_castnode_marks)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->node_marks) * max_nodes_per_window_ * max_poas_); - graph_details_d->check_aligned_nodes = reinterpret_castcheck_aligned_nodes)>(&block_data_d_[offset_d_]); + graph_details_d->check_aligned_nodes = reinterpret_castcheck_aligned_nodes)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->check_aligned_nodes) * max_nodes_per_window_ * max_poas_); - graph_details_d->nodes_to_visit = reinterpret_castnodes_to_visit)>(&block_data_d_[offset_d_]); + graph_details_d->nodes_to_visit = reinterpret_castnodes_to_visit)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->nodes_to_visit) * max_nodes_per_window_ * max_poas_); - graph_details_d->node_coverage_counts = reinterpret_castnode_coverage_counts)>(&block_data_d_[offset_d_]); + graph_details_d->node_coverage_counts = reinterpret_castnode_coverage_counts)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->node_coverage_counts) * max_nodes_per_window_ * max_poas_); if (output_mask_ & OutputType::msa) { - graph_details_d->outgoing_edges_coverage = reinterpret_castoutgoing_edges_coverage)>(&block_data_d_[offset_d_]); + graph_details_d->outgoing_edges_coverage = reinterpret_castoutgoing_edges_coverage)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->outgoing_edges_coverage) * max_nodes_per_window_ * CUDAPOA_MAX_NODE_EDGES * max_sequences_per_poa_ * max_poas_); - graph_details_d->outgoing_edges_coverage_count = reinterpret_castoutgoing_edges_coverage_count)>(&block_data_d_[offset_d_]); + graph_details_d->outgoing_edges_coverage_count = reinterpret_castoutgoing_edges_coverage_count)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->outgoing_edges_coverage_count) * max_nodes_per_window_ * CUDAPOA_MAX_NODE_EDGES * max_poas_); - graph_details_d->node_id_to_msa_pos = reinterpret_castnode_id_to_msa_pos)>(&block_data_d_[offset_d_]); + graph_details_d->node_id_to_msa_pos = reinterpret_castnode_id_to_msa_pos)>(&block_data_d[offset_d_]); offset_d_ += cudautils::align(sizeof(*graph_details_d->node_id_to_msa_pos) * max_nodes_per_window_ * max_poas_); } @@ -296,15 +331,17 @@ class BatchBlock uint8_t* get_block_device() { - return block_data_d_; + return block_data_d_.data(); } int32_t get_max_poas() const { return max_poas_; }; static int64_t compute_device_memory_per_poa(const BatchConfig& batch_size, const bool msa_flag, const bool variable_bands = false) { - int64_t device_size_per_poa = 0; - int32_t max_nodes_per_graph = batch_size.max_nodes_per_graph; + int64_t device_size_per_poa = 0; + int32_t max_nodes_per_graph = batch_size.max_nodes_per_graph; + bool traceback = batch_size.band_mode == static_band_traceback || batch_size.band_mode == adaptive_band_traceback; + int32_t traceback_score_matrix_size = batch_size.matrix_sequence_dimension * batch_size.max_banded_pred_distance; // for output - device device_size_per_poa += batch_size.max_consensus_size * sizeof(*OutputDetails::consensus); // output_details_d_->consensus @@ -338,13 +375,13 @@ class BatchBlock device_size_per_poa += (msa_flag) ? sizeof(*GraphDetails::outgoing_edges_coverage_count) * max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES : 0; // graph_details_d_->outgoing_edges_coverage_count device_size_per_poa += (msa_flag) ? sizeof(*GraphDetails::node_id_to_msa_pos) * max_nodes_per_graph : 0; // graph_details_d_->node_id_to_msa_pos // for alignment - device - device_size_per_poa += sizeof(*AlignmentDetails::alignment_graph) * max_nodes_per_graph; // alignment_details_d_->alignment_graph - device_size_per_poa += sizeof(*AlignmentDetails::alignment_read) * max_nodes_per_graph; // alignment_details_d_->alignment_read - device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_starts) * max_nodes_per_graph : 0; // alignment_details_d_->band_starts - device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_widths) * max_nodes_per_graph : 0; // alignment_details_d_->band_widths - device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_head_indices) * max_nodes_per_graph : 0; // alignment_details_d_->band_head_indices - device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_max_indices) * max_nodes_per_graph : 0; // alignment_details_d_->band_max_indices - + device_size_per_poa += sizeof(*AlignmentDetails::alignment_graph) * max_nodes_per_graph; // alignment_details_d_->alignment_graph + device_size_per_poa += sizeof(*AlignmentDetails::alignment_read) * max_nodes_per_graph; // alignment_details_d_->alignment_read + device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_starts) * max_nodes_per_graph : 0; // alignment_details_d_->band_starts + device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_widths) * max_nodes_per_graph : 0; // alignment_details_d_->band_widths + device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_head_indices) * max_nodes_per_graph : 0; // alignment_details_d_->band_head_indices + device_size_per_poa += variable_bands ? sizeof(*AlignmentDetails::band_max_indices) * max_nodes_per_graph : 0; // alignment_details_d_->band_max_indices + device_size_per_poa += traceback ? sizeof(*AlignmentDetails::scores) * traceback_score_matrix_size : 0; // alignment_details_d_->scores (only for traceback banded modes) return device_size_per_poa; } @@ -380,33 +417,42 @@ class BatchBlock cudaMemGetInfo(&free, &total); size_t mem_per_batch = memory_usage_quota * free; // Using memory_usage_quota of GPU available memory for cudapoa batch. - int64_t sizeof_ScoreT = 2; + int64_t sizeof_ScoreT = sizeof(int16_t); + int64_t sizeof_TraceT = use16bitTrace(batch_size) ? sizeof(int16_t) : sizeof(int8_t); int64_t device_size_per_poa = 0; if (use32bitScore(batch_size, gap_score, mismatch_score, match_score)) { - sizeof_ScoreT = 4; + sizeof_ScoreT = sizeof(int32_t); if (use32bitSize(batch_size)) { - device_size_per_poa = BatchBlock::compute_device_memory_per_poa(batch_size, msa_flag); + device_size_per_poa = BatchBlock::compute_device_memory_per_poa(batch_size, msa_flag); } else { - device_size_per_poa = BatchBlock::compute_device_memory_per_poa(batch_size, msa_flag); + device_size_per_poa = BatchBlock::compute_device_memory_per_poa(batch_size, msa_flag); } } else { // if ScoreT is 16-bit, it's safe to assume SizeT is also 16-bit - device_size_per_poa = BatchBlock::compute_device_memory_per_poa(batch_size, msa_flag); + device_size_per_poa = BatchBlock::compute_device_memory_per_poa(batch_size, msa_flag); } - // Compute required memory for score matrix - int64_t device_size_per_score_matrix = static_cast(batch_size.matrix_sequence_dimension) * - static_cast(batch_size.matrix_graph_dimension) * sizeof_ScoreT; + // Compute required memory for score or backtracking matrix + int64_t device_size_per_matrix = static_cast(batch_size.matrix_sequence_dimension) * + static_cast(batch_size.max_nodes_per_graph); + if (batch_size.band_mode == BandMode::static_band_traceback || batch_size.band_mode == BandMode::adaptive_band_traceback) + { + device_size_per_matrix *= sizeof_TraceT; + } + else + { + device_size_per_matrix *= sizeof_ScoreT; + } // Calculate max POAs possible based on available memory. - int64_t max_poas = mem_per_batch / (device_size_per_poa + device_size_per_score_matrix); + int64_t max_poas = mem_per_batch / (device_size_per_poa + device_size_per_matrix); return max_poas; } @@ -432,7 +478,7 @@ class BatchBlock host_size_fixed += sizeof(GraphDetails); // graph_details_h_ host_size_fixed += sizeof(GraphDetails); // graph_details_d_ // for alignment - host - host_size_fixed += sizeof(AlignmentDetails); // alignment_details_d_ + host_size_fixed += sizeof(AlignmentDetails); // alignment_details_d_ return std::make_tuple(host_size_fixed, device_size_fixed, host_size_per_poa, device_size_per_poa); } @@ -450,7 +496,7 @@ class BatchBlock // Pointer for block data on host and device uint8_t* block_data_h_; - uint8_t* block_data_d_; + device_buffer block_data_d_; // Accumulator for the memory size int64_t total_h_ = 0; @@ -463,8 +509,10 @@ class BatchBlock int64_t input_size_ = 0; int64_t output_size_ = 0; int32_t max_nodes_per_window_ = 0; + int32_t score_matrix_height_ = 0; + int32_t score_matrix_width_ = 0; + bool traceback_alignment_ = false; int32_t device_id_; - // Bit field for output type int8_t output_mask_; }; diff --git a/cudapoa/src/application_parameters.cpp b/cudapoa/src/application_parameters.cpp index 1a5bebe5a..797c6f71d 100644 --- a/cudapoa/src/application_parameters.cpp +++ b/cudapoa/src/application_parameters.cpp @@ -40,6 +40,8 @@ ApplicationParameters::ApplicationParameters(int argc, char* argv[]) {"band-mode", required_argument, 0, 'b'}, {"band-width", required_argument, 0, 'w'}, {"adaptive-storage", required_argument, 0, 's'}, + {"graph-length", required_argument, 0, 'l'}, + {"pred-distance", required_argument, 0, 'D'}, {"dot", required_argument, 0, 'd'}, {"gfa", required_argument, 0, 'G'}, {"max-groups", required_argument, 0, 'M'}, @@ -51,8 +53,7 @@ ApplicationParameters::ApplicationParameters(int argc, char* argv[]) {"help", no_argument, 0, 'h'}, }; - - std::string optstring = "i:ab:w:s:d:G:M:R:m:n:g:vh"; + std::string optstring = "i:ab:w:s:l:D:d:G:M:R:m:n:g:vh"; int32_t argument = 0; while ((argument = getopt_long(argc, argv, optstring.c_str(), options, nullptr)) != -1) @@ -66,9 +67,9 @@ ApplicationParameters::ApplicationParameters(int argc, char* argv[]) msa = true; break; case 'b': - if (std::stoi(optarg) < 0 || std::stoi(optarg) > 2) + if (std::stoi(optarg) < 0 || std::stoi(optarg) > 4) { - throw std::runtime_error("band-mode must be either 0 for full bands, 1 for static bands or 2 for adaptive bands"); + throw std::runtime_error("band-mode must be either 0 for full bands, 1 for static bands, 2 for adaptive bands, 3 and 4 for static and adaptive bands with traceback"); } band_mode = static_cast(std::stoi(optarg)); break; @@ -78,6 +79,16 @@ ApplicationParameters::ApplicationParameters(int argc, char* argv[]) case 's': adaptive_storage = std::stof(optarg); break; + case 'l': + graph_length = std::stof(optarg); + break; + case 'D': + if (std::stoi(optarg) <= 0) + { + throw std::runtime_error("pred-distance must be an integer greater than 0"); + } + predecessor_disance = std::stoi(optarg); + break; case 'd': graph_output_path = std::string(optarg); break; @@ -190,7 +201,7 @@ void ApplicationParameters::help(int32_t exit_code) generates msa if this flag is passed [default: consensus])" << R"( -b, --band-mode - selects banding mode, 0: full-alignment, 1: static band, 2: adaptive band [2])" + selects banding mode, 0: full-alignment, 1: static band, 2: adaptive band, 3: traceback static band, 4: traceback adaptive band [2])" << R"( -w, --band-width band-width for banded alignment (must be multiple of 128) [256])" @@ -198,6 +209,12 @@ void ApplicationParameters::help(int32_t exit_code) -s, --adaptive-storage factor to accommodate extra memory for adaptive score matrix. The factor represents ratio of adaptive-banded score matrix to static-banded score matrix [2.0])" << R"( + -l, --graph-length + factor to determine maximum length of POA graph. The factor represents ratio of graph length to maximum sequence length in POA group [3.0])" + << R"( + -D, --pred-distance + maximum distance of predecessor nodes that are considered in Needleman-Wunsch computations for static or adaptive-banded. If 0, it will be set equal to 2 x band-width [0])" + << R"( -d, --dot output path for printing graph in DOT format [disabled])" << R"( diff --git a/cudapoa/src/application_parameters.hpp b/cudapoa/src/application_parameters.hpp index 45600c1c6..2cf92706f 100644 --- a/cudapoa/src/application_parameters.hpp +++ b/cudapoa/src/application_parameters.hpp @@ -39,17 +39,19 @@ class ApplicationParameters std::vector input_paths; std::string graph_output_path; - bool output_gfa = false; - bool all_fasta = true; - bool msa = false; // consensus by default - BandMode band_mode = BandMode::adaptive_band; - int32_t band_width = 256; // Band width for banded mode - int32_t max_groups = -1; // -1 => infinite - int32_t mismatch_score = -6; - int32_t gap_score = -8; - int32_t match_score = 8; - double gpu_mem_allocation = 0.9; - float adaptive_storage = 2.0f; + bool output_gfa = false; + bool all_fasta = true; + bool msa = false; // consensus by default + BandMode band_mode = BandMode::adaptive_band; + int32_t band_width = 256; // Band width for banded mode + int32_t max_groups = -1; // -1 => infinite + int32_t mismatch_score = -6; + int32_t gap_score = -8; + int32_t match_score = 8; + double gpu_mem_allocation = 0.9; + float adaptive_storage = 2.0f; + float graph_length = 3.0f; + int32_t predecessor_disance = 0; private: /// \brief verifies input file formats diff --git a/cudapoa/src/batch.cu b/cudapoa/src/batch.cu index bf24667a0..18361fd63 100644 --- a/cudapoa/src/batch.cu +++ b/cudapoa/src/batch.cu @@ -32,7 +32,8 @@ namespace cudapoa /// constructor- set other parameters based on a minimum set of input arguments BatchConfig::BatchConfig(int32_t max_seq_sz /*= 1024*/, int32_t max_seq_per_poa /*= 100*/, int32_t band_width /*= 256*/, - BandMode banding /*= BandMode::full_band*/, float adapive_storage_factor /*= 2.0*/) + BandMode banding /*= BandMode::full_band*/, float adapive_storage_factor /*= 2.0*/, float graph_length_factor /*= 3.0*/, + int32_t max_pred_dist /*= 0*/) /// ensure a 4-byte boundary alignment for any allocated buffer : max_sequence_size(max_seq_sz) , max_consensus_size(2 * max_sequence_size) @@ -40,31 +41,29 @@ BatchConfig::BatchConfig(int32_t max_seq_sz /*= 1024*/, int32_t max_seq_per_poa , alignment_band_width(cudautils::align(band_width)) , max_sequences_per_poa(max_seq_per_poa) , band_mode(banding) + , max_banded_pred_distance(max_pred_dist > 0 ? max_pred_dist : 2 * cudautils::align(band_width)) { + max_nodes_per_graph = cudautils::align(graph_length_factor * max_sequence_size); + if (banding == BandMode::full_band) { - max_nodes_per_graph = cudautils::align(3 * max_sequence_size); - matrix_graph_dimension = cudautils::align(max_nodes_per_graph); - matrix_sequence_dimension = cudautils::align(max_sequence_size); + matrix_sequence_dimension = cudautils::align(max_sequence_size); } - else if (banding == BandMode::static_band) + else if (banding == BandMode::static_band || banding == BandMode::static_band_traceback) { - max_nodes_per_graph = cudautils::align(4 * max_sequence_size); - matrix_graph_dimension = cudautils::align(max_nodes_per_graph); - // 8 = CUDAPOA_BANDED_MATRIX_RIGHT_PADDING - matrix_sequence_dimension = cudautils::align(alignment_band_width + 8); + matrix_sequence_dimension = cudautils::align(alignment_band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); } - else // BandMode::adaptive_band + else // BandMode::adaptive_band || BandMode::adaptive_band_traceback { - max_nodes_per_graph = cudautils::align(4 * max_sequence_size); - matrix_graph_dimension = cudautils::align(max_nodes_per_graph); - // 8 = CUDAPOA_BANDED_MATRIX_RIGHT_PADDING, *2 is to reserve extra memory for cases with extended band-width - matrix_sequence_dimension = cudautils::align(adapive_storage_factor * (alignment_band_width + 8)); + // adapive_storage_factor is to reserve extra memory for cases with extended band-width + matrix_sequence_dimension = cudautils::align(adapive_storage_factor * (alignment_band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING)); } throw_on_negative(max_seq_sz, "max_sequence_size cannot be negative."); throw_on_negative(max_seq_per_poa, "max_sequences_per_poa cannot be negative."); throw_on_negative(band_width, "alignment_band_width cannot be negative."); + throw_on_negative(max_nodes_per_graph, "max_nodes_per_graph cannot be negative."); + if (alignment_band_width != band_width) { std::cerr << "Band-width should be multiple of 128. The input was changed from " << band_width << " to " << alignment_band_width << std::endl; @@ -72,24 +71,25 @@ BatchConfig::BatchConfig(int32_t max_seq_sz /*= 1024*/, int32_t max_seq_per_poa } /// constructor- set all parameters separately -BatchConfig::BatchConfig(int32_t max_seq_sz, int32_t max_consensus_sz, int32_t max_nodes_per_w, - int32_t band_width, int32_t max_seq_per_poa, int32_t matrix_seq_dim, BandMode banding) +BatchConfig::BatchConfig(int32_t max_seq_sz, int32_t max_consensus_sz, int32_t max_nodes_per_poa, int32_t band_width, + int32_t max_seq_per_poa, int32_t matrix_seq_dim, BandMode banding, int32_t max_pred_distance) /// ensure a 4-byte boundary alignment for any allocated buffer : max_sequence_size(max_seq_sz) , max_consensus_size(max_consensus_sz) - , max_nodes_per_graph(cudautils::align(max_nodes_per_w)) - , matrix_graph_dimension(cudautils::align(max_nodes_per_graph)) - , matrix_sequence_dimension(cudautils::align(matrix_seq_dim)) + , max_nodes_per_graph(cudautils::align(max_nodes_per_poa)) + , matrix_sequence_dimension(cudautils::align(matrix_seq_dim)) /// ensure 128-alignment for band_width size , alignment_band_width(cudautils::align(band_width)) , max_sequences_per_poa(max_seq_per_poa) , band_mode(banding) + , max_banded_pred_distance(max_pred_distance) { throw_on_negative(max_seq_sz, "max_sequence_size cannot be negative."); throw_on_negative(max_consensus_sz, "max_consensus_size cannot be negative."); - throw_on_negative(max_nodes_per_w, "max_nodes_per_graph cannot be negative."); + throw_on_negative(max_nodes_per_poa, "max_nodes_per_graph cannot be negative."); throw_on_negative(max_seq_per_poa, "max_sequences_per_poa cannot be negative."); throw_on_negative(band_width, "alignment_band_width cannot be negative."); + throw_on_negative(max_pred_distance, "max_banded_pred_distance cannot be negative."); if (max_nodes_per_graph < max_sequence_size) throw std::invalid_argument("max_nodes_per_graph should be greater than or equal to max_sequence_size."); @@ -105,7 +105,8 @@ BatchConfig::BatchConfig(int32_t max_seq_sz, int32_t max_consensus_sz, int32_t m std::unique_ptr create_batch(int32_t device_id, cudaStream_t stream, - size_t max_mem, + DefaultDeviceAllocator allocator, + int64_t max_mem, int8_t output_mask, const BatchConfig& batch_size, int16_t gap_score, @@ -116,39 +117,118 @@ std::unique_ptr create_batch(int32_t device_id, { if (use32bitSize(batch_size)) { - return std::make_unique>(device_id, - stream, - max_mem, - output_mask, - batch_size, - (int32_t)gap_score, - (int32_t)mismatch_score, - (int32_t)match_score); + if (use16bitTrace(batch_size)) + { + return std::make_unique>(device_id, + stream, + allocator, + max_mem, + output_mask, + batch_size, + gap_score, + mismatch_score, + match_score); + } + else + { + return std::make_unique>(device_id, + stream, + allocator, + max_mem, + output_mask, + batch_size, + gap_score, + mismatch_score, + match_score); + } } else { - return std::make_unique>(device_id, - stream, - max_mem, - output_mask, - batch_size, - (int32_t)gap_score, - (int32_t)mismatch_score, - (int32_t)match_score); + if (use16bitTrace(batch_size)) + { + return std::make_unique>(device_id, + stream, + allocator, + max_mem, + output_mask, + batch_size, + gap_score, + mismatch_score, + match_score); + } + else + { + return std::make_unique>(device_id, + stream, + allocator, + max_mem, + output_mask, + batch_size, + gap_score, + mismatch_score, + match_score); + } } } else { // if ScoreT is 16-bit, then it's safe to assume SizeT is 16-bit - return std::make_unique>(device_id, - stream, - max_mem, - output_mask, - batch_size, - gap_score, - mismatch_score, - match_score); + if (use16bitTrace(batch_size)) + { + return std::make_unique>(device_id, + stream, + allocator, + max_mem, + output_mask, + batch_size, + gap_score, + mismatch_score, + match_score); + } + else + { + return std::make_unique>(device_id, + stream, + allocator, + max_mem, + output_mask, + batch_size, + gap_score, + mismatch_score, + match_score); + } + } +} + +std::unique_ptr create_batch(int32_t device_id, + cudaStream_t stream, + int64_t max_mem, + int8_t output_mask, + const BatchConfig& batch_size, + int16_t gap_score, + int16_t mismatch_score, + int16_t match_score) +{ + if (max_mem < -1) + { + throw std::invalid_argument("max_mem has to be either -1 (=all available GPU memory) or greater or equal than 0."); + } +#ifdef GW_ENABLE_CACHING_ALLOCATOR + // uses CachingDeviceAllocator + if (max_mem == -1) + { + max_mem = claraparabricks::genomeworks::cudautils::find_largest_contiguous_device_memory_section(); + if (max_mem == 0) + { + throw std::runtime_error("No memory available for caching"); + } } + claraparabricks::genomeworks::DefaultDeviceAllocator allocator(max_mem); +#else + // uses CudaMallocAllocator + claraparabricks::genomeworks::DefaultDeviceAllocator allocator; +#endif + return create_batch(device_id, stream, allocator, max_mem, output_mask, batch_size, gap_score, mismatch_score, match_score); } } // namespace cudapoa diff --git a/cudapoa/src/cudapoa.cpp b/cudapoa/src/cudapoa.cpp index 9699c663d..1069250c3 100644 --- a/cudapoa/src/cudapoa.cpp +++ b/cudapoa/src/cudapoa.cpp @@ -17,6 +17,8 @@ #include #include +#include + namespace claraparabricks { @@ -34,6 +36,55 @@ StatusType Init() return StatusType::success; } +void decode_error(StatusType error_type, std::string& error_message, std::string& error_hint) +{ + switch (error_type) + { + case StatusType::exceeded_maximum_poas: + error_message = "Kernel Error: Number of groups per batch exceeded maximum POAs."; + error_hint = "Suggestion : Evaluate maximum number of groups per batch using BatchBlock::estimate_max_poas()."; + break; + case StatusType::exceeded_maximum_sequence_size: + error_message = "Kernel Error: Input read length or output consensus/MSA sequence length exceeded max sequence size."; + error_hint = "Suggestion : Check BatchConfig::max_sequence_size and BatchConfig::max_consensus_size, increase if necessary."; + break; + case StatusType::exceeded_maximum_sequences_per_poa: + error_message = "Kernel Error: Exceeded maximum number of reads per POA."; + error_hint = "Suggestion : Check BatchConfig::max_sequences_per_poa and increase if necessary."; + break; + case StatusType::node_count_exceeded_maximum_graph_size: + error_message = "Kernel Error: Node count exceeded maximum nodes per POA graph."; + error_hint = "Suggestion : Check BatchConfig::max_nodes_per_graph and increase if necessary."; + break; + case StatusType::edge_count_exceeded_maximum_graph_size: + error_message = "Kernel Error: Edge count exceeded maximum edges per graph."; + error_hint = "Suggestion : Check default value of CUDAPOA_MAX_NODE_EDGES, note that increasing this macro would increase memory usage per POA."; + break; + case StatusType::exceeded_adaptive_banded_matrix_size: + error_message = "Kernel Error: Allocated buffer for score/traceback matrix in adaptive banding is not large enough."; + error_hint = "Suggestion : Check BatchConfig::matrix_sequence_dimension and increase if necessary."; + break; + case StatusType::exceeded_maximum_predecessor_distance: + error_message = "Kernel Error: Set value for maximum predecessor distance in Needleman-Wunsch algorithm with traceback buffer is not large enough."; + error_hint = "Suggestion : Check BatchConfig::max_banded_pred_distance and increase if necessary."; + break; + case StatusType::loop_count_exceeded_upper_bound: + error_message = "Kernel Error: Traceback in Needleman-Wunsch algorithm failed."; + error_hint = "Suggestion : You may retry with a different banding mode."; + break; + case StatusType::output_type_unavailable: + error_message = "Kernel Error: Output type not available."; + error_hint = "Suggestion : Check MSA/Consensus selection for output type."; + break; + case StatusType::generic_error: + error_message = "Unknown error."; + error_hint = ""; + break; + default: + throw std::runtime_error("Unknown error type detected."); + } +} + } // namespace cudapoa } // namespace genomeworks diff --git a/cudapoa/src/cudapoa_add_alignment.cuh b/cudapoa/src/cudapoa_add_alignment.cuh index 92b3f9f72..03c0e14a5 100644 --- a/cudapoa/src/cudapoa_add_alignment.cuh +++ b/cudapoa/src/cudapoa_add_alignment.cuh @@ -352,25 +352,25 @@ void addAlignment(uint8_t* nodes, uint32_t max_sequences_per_poa, uint32_t max_limit_nodes_per_window) { - addAlignmentKernel<<<1, 1>>>(nodes, - node_count, - node_alignments, node_alignment_count, - incoming_edges, incoming_edge_count, - outgoing_edges, outgoing_edge_count, - incoming_edge_w, - alignment_length, - graph, - alignment_graph, - read, - alignment_read, - node_coverage_counts, - base_weights, - sequence_begin_nodes_ids, - outgoing_edges_coverage, - outgoing_edges_coverage_count, - s, - max_sequences_per_poa, - max_limit_nodes_per_window); + addAlignmentKernel<<<1, 1>>>(nodes, + node_count, + node_alignments, node_alignment_count, + incoming_edges, incoming_edge_count, + outgoing_edges, outgoing_edge_count, + incoming_edge_w, + alignment_length, + graph, + alignment_graph, + read, + alignment_read, + node_coverage_counts, + base_weights, + sequence_begin_nodes_ids, + outgoing_edges_coverage, + outgoing_edges_coverage_count, + s, + max_sequences_per_poa, + max_limit_nodes_per_window); GW_CU_CHECK_ERR(cudaPeekAtLastError()); } diff --git a/cudapoa/src/cudapoa_batch.cuh b/cudapoa/src/cudapoa_batch.cuh index c6e938db2..70d7ee956 100644 --- a/cudapoa/src/cudapoa_batch.cuh +++ b/cudapoa/src/cudapoa_batch.cuh @@ -59,12 +59,12 @@ namespace cudapoa /// \class /// Batched GPU CUDA POA object -template +template class CudapoaBatch : public Batch { public: - CudapoaBatch(int32_t device_id, cudaStream_t stream, size_t max_gpu_mem, int8_t output_mask, - const BatchConfig& batch_size, ScoreT gap_score = -8, ScoreT mismatch_score = -6, ScoreT match_score = 8) + CudapoaBatch(int32_t device_id, cudaStream_t stream, DefaultDeviceAllocator allocator, int64_t max_mem, int8_t output_mask, + const BatchConfig& batch_size, int32_t gap_score = -8, int32_t mismatch_score = -6, int32_t match_score = 8) : max_sequences_per_poa_(throw_on_negative(batch_size.max_sequences_per_poa, "Maximum sequences per POA has to be non-negative")) , device_id_(throw_on_negative(device_id, "Device ID has to be non-negative")) , stream_(stream) @@ -73,12 +73,11 @@ public: , gap_score_(gap_score) , mismatch_score_(mismatch_score) , match_score_(match_score) - , banded_alignment_(batch_size.band_mode == BandMode::static_band) - , adaptive_banded_(batch_size.band_mode == BandMode::adaptive_band) - , batch_block_(new BatchBlock(device_id, - max_gpu_mem, - output_mask, - batch_size_)) + , batch_block_(new BatchBlock(device_id, + allocator, + max_mem, + output_mask, + batch_size_)) , max_poas_(batch_block_->get_max_poas()) { // Set CUDA device @@ -178,20 +177,18 @@ public: std::string msg = " Launching kernel for " + std::to_string(poa_count_) + " on device "; print_batch_debug_message(msg); - generatePOA(output_details_d_, - input_details_d_, - poa_count_, - stream_, - alignment_details_d_, - graph_details_d_, - gap_score_, - mismatch_score_, - match_score_, - banded_alignment_, - adaptive_banded_, - max_sequences_per_poa_, - output_mask_, - batch_size_); + generatePOA(output_details_d_, + input_details_d_, + poa_count_, + stream_, + alignment_details_d_, + graph_details_d_, + gap_score_, + mismatch_score_, + match_score_, + max_sequences_per_poa_, + output_mask_, + batch_size_); msg = " Launched kernel on device "; print_batch_debug_message(msg); @@ -404,7 +401,7 @@ public: num_nucleotides_copied_ = 0; global_sequence_idx_ = 0; next_scores_offset_ = 0; - avail_scorebuf_mem_ = alignment_details_d_->scorebuf_alloc_size; + avail_buf_mem_ = alignment_details_d_->scorebuf_alloc_size; } protected: @@ -443,37 +440,12 @@ protected: void decode_cudapoa_kernel_error(genomeworks::cudapoa::StatusType error_type, std::vector& output_status) { - switch (error_type) - { - case genomeworks::cudapoa::StatusType::node_count_exceeded_maximum_graph_size: - GW_LOG_WARN("Kernel Error:: Node count exceeded maximum nodes per graph in batch {}\n", bid_); - output_status.emplace_back(error_type); - break; - case genomeworks::cudapoa::StatusType::edge_count_exceeded_maximum_graph_size: - GW_LOG_WARN("Kernel Error:: Edge count exceeded maximum edges per graph in batch {}\n", bid_); - output_status.emplace_back(error_type); - break; - case genomeworks::cudapoa::StatusType::seq_len_exceeded_maximum_nodes_per_window: - GW_LOG_WARN("Kernel Error:: Sequence length exceeded maximum nodes per window in batch {}\n", bid_); - output_status.emplace_back(error_type); - break; - case genomeworks::cudapoa::StatusType::loop_count_exceeded_upper_bound: - GW_LOG_WARN("Kernel Error:: Loop count exceeded upper bound in nw algorithm in batch {}\n", bid_); - output_status.emplace_back(error_type); - break; - case genomeworks::cudapoa::StatusType::exceeded_adaptive_banded_matrix_size: - GW_LOG_WARN("Kernel Error:: Band width set for adaptive matrix allocation is too small in batch {}\n", bid_); - output_status.emplace_back(error_type); - break; - case genomeworks::cudapoa::StatusType::exceeded_maximum_sequence_size: - GW_LOG_WARN("Kernel Error:: Consensus/MSA sequence size exceeded max sequence size in batch {}\n", bid_); - output_status.emplace_back(error_type); - break; - default: - GW_LOG_WARN("Kernel Error:: Unknown error in batch {}\n", bid_); - output_status.emplace_back(error_type); - break; - } + std::string error_message; + std::string error_hint; + decode_error(error_type, error_message, error_hint); + error_message = error_message + " in batch {}\n" + error_hint; + GW_LOG_WARN(error_message.c_str(), bid_); + output_status.emplace_back(error_type); } // Add new partial order alignment to batch. @@ -504,7 +476,7 @@ protected: } WindowDetails* window_details = &(input_details_h_->window_details[poa_count_ - 1]); - int32_t scores_width_ = cudautils::align(seq_len + 1 + CELLS_PER_THREAD); + int32_t scores_width_ = cudautils::align(seq_len + 1 + CUDAPOA_CELLS_PER_THREAD); if (scores_width_ > window_details->scores_width) { next_scores_offset_ += (scores_width_ - window_details->scores_width); @@ -541,33 +513,40 @@ protected: } input_details_h_->sequence_lengths[global_sequence_idx_] = seq_len; - num_nucleotides_copied_ += seq_len; + // to be aligned with SeqT4 struct size, pad sequence length to be multiple of 4. + // Note: num_nucleotides_copied_ is used to define allocated space per read on device as well as on host, + // therefore it is important to reflect any changes in the following line in the corresponding device code as well + num_nucleotides_copied_ += cudautils::align(seq_len); + global_sequence_idx_++; return StatusType::success; } - // Check if seq length can fit in available scoring matrix memory. + // Check if intermediate data for seq length can fit in available scoring/traceback buffer bool reserve_buf(int32_t max_seq_length) { - int32_t max_graph_dimension = batch_size_.matrix_graph_dimension; - - int32_t scores_width = (banded_alignment_ || adaptive_banded_) ? batch_size_.matrix_sequence_dimension : cudautils::align(max_seq_length + 1 + CELLS_PER_THREAD); - size_t scores_size = static_cast(scores_width) * static_cast(max_graph_dimension) * sizeof(ScoreT); - - if (scores_size > avail_scorebuf_mem_) + int32_t matrix_height = batch_size_.max_nodes_per_graph; + // matrix width for full_band is based on the current group max_seq_length as opposed to batch_size_.matrix_sequence_dimension. + // The latter is based on the largest group in the batch and is more conservative + int32_t matrix_width = (batch_size_.band_mode != BandMode::full_band) ? batch_size_.matrix_sequence_dimension : cudautils::align(max_seq_length + 1 + CUDAPOA_CELLS_PER_THREAD); + // in traceback alignments avail_buf_mem_ is dedicated to traceback matrix, otherwise it is being used for score matrix + size_t required_size = static_cast(matrix_width) * static_cast(matrix_height); + required_size *= (batch_size_.band_mode == static_band_traceback || batch_size_.band_mode == adaptive_band_traceback) ? sizeof(TraceT) : sizeof(ScoreT); + + if (required_size > avail_buf_mem_) { if (get_total_poas() == 0) { - std::cout << "Memory available " << std::fixed << std::setprecision(2) << (static_cast(avail_scorebuf_mem_)) / 1024. / 1024. / 1024.; - std::cout << "GB, Memory required " << (static_cast(scores_size)) / 1024. / 1024. / 1024.; - std::cout << "GB (sequence length " << max_seq_length << ", graph length " << max_graph_dimension << ")" << std::endl; + std::cout << "Memory available " << std::fixed << std::setprecision(2) << (static_cast(avail_buf_mem_)) / 1024. / 1024. / 1024.; + std::cout << "GB, Memory required " << (static_cast(required_size)) / 1024. / 1024. / 1024.; + std::cout << "GB (sequence length " << max_seq_length << ", graph length " << matrix_height << ")" << std::endl; } return false; } else { - avail_scorebuf_mem_ -= scores_size; + avail_buf_mem_ -= required_size; return true; } } @@ -589,9 +568,9 @@ protected: BatchConfig batch_size_; // Gap, mismatch and match scores for NW dynamic programming loop. - ScoreT gap_score_; - ScoreT mismatch_score_; - ScoreT match_score_; + int32_t gap_score_; + int32_t mismatch_score_; + int32_t match_score_; // Host and device buffer for output data. OutputDetails* output_details_h_; @@ -602,7 +581,7 @@ protected: InputDetails* input_details_h_; // Device buffer struct for alignment details - AlignmentDetails* alignment_details_d_; + AlignmentDetails* alignment_details_d_; // Device buffer struct for graph details GraphDetails* graph_details_d_; @@ -620,22 +599,18 @@ protected: // Global sequence index. int32_t global_sequence_idx_ = 0; - // Remaining scores buffer memory available for use. - size_t avail_scorebuf_mem_ = 0; + // Remaining buffer memory available for scores matrices in case of full alignment, and for traceback matrices in case of banded alignment + size_t avail_buf_mem_ = 0; // Temporary variable to compute the offset to scorebuf. size_t next_scores_offset_ = 0; - // Use banded POA alignment - bool banded_alignment_; - bool adaptive_banded_; - // flag that enables some extra buffers to accommodate fully adaptive bands with variable width and arbitrary location // disabled for current implementation, can be enabled for possible future variants of adaptive alignment algorithm bool variable_band_ = false; // Pointer of a seperate class BatchBlock that implements details on calculating and allocating the memory for each batch - std::unique_ptr> batch_block_; + std::unique_ptr> batch_block_; // Maximum POAs to process in batch. int32_t max_poas_ = 0; @@ -645,8 +620,8 @@ public: static int32_t batches; }; -template -int32_t CudapoaBatch::batches = 0; +template +int32_t CudapoaBatch::batches = 0; /// \} diff --git a/cudapoa/src/cudapoa_kernels.cuh b/cudapoa/src/cudapoa_kernels.cuh index aaa48c1e3..e8a115bca 100644 --- a/cudapoa/src/cudapoa_kernels.cuh +++ b/cudapoa/src/cudapoa_kernels.cuh @@ -19,7 +19,7 @@ #include "cudapoa_nw.cuh" #include "cudapoa_nw_banded.cuh" -#include "cudapoa_nw_adaptive_banded.cuh" +#include "cudapoa_nw_tb_banded.cuh" #include "cudapoa_topsort.cuh" #include "cudapoa_add_alignment.cuh" #include "cudapoa_generate_consensus.cuh" @@ -29,7 +29,8 @@ #include // considering 65536 register file size, __launch_bounds__(1024) translates to max 64 register usage -#define GW_POA_KERNELS_MAX_THREADS_PER_BLOCK 1024 +#define GW_POA_KERNELS_MAX_THREADS_PER_BLOCK_64_REGISTERS 1024 +#define GW_POA_KERNELS_MAX_THREADS_PER_BLOCK_72_REGISTERS 896 namespace claraparabricks { @@ -51,8 +52,8 @@ namespace cudapoa * @param[in] window_details_d Device buffer with structs encapsulating sequence details per window * @param[in] total_windows Total number of windows to process * @param[in] scores_d Device scratch space that scores alignment matrix score - * @param[in] alignment_graph_d Device scratch space for backtrace alignment of graph - * @param[in] alignment_read_d Device scratch space for backtrace alignment of sequence + * @param[in] alignment_graph_d Device scratch space for traceback alignment of graph + * @param[in] alignment_read_d Device scratch space for traceback alignment of sequence * @param[in] nodes_d Device scratch space for storing unique nodes in graph * @param[in] incoming_edges_d Device scratch space for storing incoming edges per node * @param[in] incoming_edges_count_d Device scratch space for storing number of incoming edges per node @@ -72,8 +73,8 @@ namespace cudapoa * @param[in] mismatch_score Score for finding a mismatch in alignment * @param[in] match_score Score for finding a match in alignment */ -template -__launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) +template +__launch_bounds__(Traceback ? GW_POA_KERNELS_MAX_THREADS_PER_BLOCK_72_REGISTERS : GW_POA_KERNELS_MAX_THREADS_PER_BLOCK_64_REGISTERS) __global__ void generatePOAKernel(uint8_t* consensus_d, uint8_t* sequences_d, int8_t* base_weights_d, @@ -106,11 +107,12 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) uint16_t* outgoing_edges_coverage_d, uint16_t* outgoing_edges_coverage_count_d, int32_t max_nodes_per_graph, - int32_t scores_matrix_height, int32_t scores_matrix_width, int32_t max_limit_consensus_size, int32_t TPB = 64, - int32_t static_band_width = 256) + int32_t static_band_width = 256, + int32_t max_pred_distance = 0, + TraceT* traceback_d = nullptr) { // shared error indicator within a warp bool warp_error = false; @@ -134,20 +136,36 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) uint16_t* node_alignment_count = &node_alignment_count_d[window_idx * max_nodes_per_graph]; uint16_t* sorted_poa_local_edge_count = &sorted_poa_local_edge_count_d[window_idx * max_nodes_per_graph]; - int32_t scores_width = window_details_d[window_idx].scores_width; - ScoreT* scores; - float banded_score_matrix_size; // using float instead of int64_t to minimize register - if (BM == BandMode::adaptive_band || BM == BandMode::static_band) + float banded_buffer_size; // using float instead of int64_t to minimize register + + TraceT* traceback = traceback_d; // only used in traceback + int32_t scores_width = window_details_d[window_idx].scores_width; // only used in non-traceback + + if (Traceback) { - banded_score_matrix_size = static_cast(scores_matrix_height) * static_cast(scores_matrix_width); - int64_t scores_offset = static_cast(banded_score_matrix_size) * static_cast(window_idx); - scores = &scores_d[scores_offset]; + // buffer size for scores, in traceback we only need to store part of the scores matrix + banded_buffer_size = static_cast(max_pred_distance) * static_cast(scores_matrix_width); + int64_t offset = static_cast(banded_buffer_size) * static_cast(window_idx); + scores = &scores_d[offset]; + // buffer size for traceback + banded_buffer_size = static_cast(max_nodes_per_graph) * static_cast(scores_matrix_width); + offset = static_cast(banded_buffer_size) * static_cast(window_idx); + traceback = &traceback_d[offset]; } else { - int64_t scores_offset = static_cast(window_details_d[window_idx].scores_offset) * static_cast(scores_matrix_height); - scores = &scores_d[scores_offset]; + if (BM == BandMode::adaptive_band || BM == BandMode::static_band) + { + banded_buffer_size = static_cast(max_nodes_per_graph) * static_cast(scores_matrix_width); + int64_t scores_offset = static_cast(banded_buffer_size) * static_cast(window_idx); + scores = &scores_d[scores_offset]; + } + else if (BM == BandMode::full_band) + { + int64_t offset = static_cast(window_details_d[window_idx].scores_offset) * static_cast(max_nodes_per_graph); + scores = &scores_d[offset]; + } } SizeT* alignment_graph = &alignment_graph_d[max_nodes_per_graph * window_idx]; @@ -221,12 +239,14 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) __syncwarp(); - // Align each subsequent read, add alignment to graph, run topoligical sort. + // Align each subsequent read, add alignment to graph, run topological sort. for (int32_t s = 1; s < num_sequences; s++) { int32_t seq_len = sequence_lengths[s]; - sequence += sequence_lengths[s - 1]; // increment the pointer so it is pointing to correct sequence data - base_weights += sequence_lengths[s - 1]; // increment the pointer so it is pointing to correct sequence data + // Note: the following 2 lines correspond to num_nucleotides_copied_ value on the host side + // therefore it is important to reflect any changes in the following 2 lines in the corresponding host code as well + sequence += cudautils::align(sequence_lengths[s - 1]); // increment the pointer so it is pointing to correct sequence data + base_weights += cudautils::align(sequence_lengths[s - 1]); // increment the pointer so it is pointing to correct sequence data if (lane_idx == 0) { @@ -245,11 +265,140 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) } // Run Needleman-Wunsch alignment between graph and new sequence. - int32_t alignment_length; + SizeT alignment_length; - if (BM == BandMode::adaptive_band) + if (Traceback) + { + // Adaptive band with traceback ------------------------------------------------------------------------ + if (BM == BandMode::adaptive_band_traceback && static_band_width < CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH) + { + alignment_length = needlemanWunschBandedTraceback(nodes, + sorted_poa, + node_id_to_pos, + sequence_lengths[0], + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + sequence, + seq_len, + scores, + traceback, + banded_buffer_size, + alignment_graph, + alignment_read, + static_band_width, + max_pred_distance, + gap_score, + mismatch_score, + match_score, + 0); + __syncwarp(); + if (alignment_length == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_LEFT || alignment_length == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_RIGHT) + { + // rerun with extended and shifted band-width + alignment_length = needlemanWunschBandedTraceback(nodes, + sorted_poa, + node_id_to_pos, + sequence_lengths[0], + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + sequence, + seq_len, + scores, + traceback, + banded_buffer_size, + alignment_graph, + alignment_read, + static_band_width, + max_pred_distance, + gap_score, + mismatch_score, + match_score, + alignment_length); + __syncwarp(); + } + } + // Static band with traceback -------------------------------------------------------------------------- + else if (BM == BandMode::static_band_traceback || (BM == BandMode::adaptive_band_traceback && static_band_width >= CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH)) + { + alignment_length = needlemanWunschBandedTraceback(nodes, + sorted_poa, + node_id_to_pos, + sequence_lengths[0], + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + sequence, + seq_len, + scores, + traceback, + banded_buffer_size, + alignment_graph, + alignment_read, + static_band_width, + max_pred_distance, + gap_score, + mismatch_score, + match_score, + alignment_length); + __syncwarp(); + } + } + else { - alignment_length = runNeedlemanWunschAdaptiveBanded(nodes, + // Adaptive band --------------------------------------------------------------------------------------- + if (BM == BandMode::adaptive_band && static_band_width < CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH) + { + // run in adaptive mode only if static_band_width < CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH + alignment_length = needlemanWunschBanded(nodes, + sorted_poa, + node_id_to_pos, + sequence_lengths[0], + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + sequence, + seq_len, + scores, + banded_buffer_size, + alignment_graph, + alignment_read, + static_band_width, + gap_score, + mismatch_score, + match_score, + 0); + __syncwarp(); + + if (alignment_length == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_LEFT || alignment_length == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_RIGHT) + { + // rerun with extended and shifted band-width + alignment_length = needlemanWunschBanded(nodes, + sorted_poa, + node_id_to_pos, + sequence_lengths[0], + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + sequence, + seq_len, + scores, + banded_buffer_size, + alignment_graph, + alignment_read, + static_band_width, + gap_score, + mismatch_score, + match_score, + alignment_length); + __syncwarp(); + } + } + // Static band --------------------------------------------------------------------------------------- + else if (BM == BandMode::static_band || (BM == BandMode::adaptive_band && static_band_width >= CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH)) + { + alignment_length = needlemanWunschBanded(nodes, sorted_poa, node_id_to_pos, sequence_lengths[0], @@ -259,83 +408,40 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) sequence, seq_len, scores, - banded_score_matrix_size, + banded_buffer_size, alignment_graph, alignment_read, static_band_width, gap_score, mismatch_score, match_score, - 0); - - __syncwarp(); - - if (alignment_length < -2) + alignment_length); + __syncwarp(); + } + // Full band ------------------------------------------------------------------------------------------- + else if (BM == BandMode::full_band) { - // rerun with extended band-width - alignment_length = runNeedlemanWunschAdaptiveBanded(nodes, - sorted_poa, - node_id_to_pos, - sequence_lengths[0], - incoming_edge_count, - incoming_edges, - outgoing_edge_count, - sequence, - seq_len, - scores, - banded_score_matrix_size, - alignment_graph, - alignment_read, - static_band_width, - gap_score, - mismatch_score, - match_score, - alignment_length); + alignment_length = needlemanWunsch(nodes, + sorted_poa, + node_id_to_pos, + sequence_lengths[0], + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + sequence, + seq_len, + scores, + scores_width, + alignment_graph, + alignment_read, + gap_score, + mismatch_score, + match_score); __syncwarp(); } } - else if (BM == BandMode::static_band) - { - alignment_length = runNeedlemanWunschBanded(nodes, - sorted_poa, - node_id_to_pos, - sequence_lengths[0], - incoming_edge_count, - incoming_edges, - outgoing_edge_count, - sequence, - seq_len, - scores, - alignment_graph, - alignment_read, - static_band_width, - gap_score, - mismatch_score, - match_score); - __syncwarp(); - } - else // BM == BandMode::full_band - { - alignment_length = runNeedlemanWunsch(nodes, - sorted_poa, - node_id_to_pos, - sequence_lengths[0], - incoming_edge_count, - incoming_edges, - outgoing_edge_count, - sequence, - seq_len, - scores, - scores_width, - alignment_graph, - alignment_read, - gap_score, - mismatch_score, - match_score); - __syncwarp(); - } - if (alignment_length == -1) + if (alignment_length == CUDAPOA_KERNEL_NW_BACKTRACKING_LOOP_FAILED) { if (lane_idx == 0) { @@ -344,7 +450,7 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) } return; } - else if (alignment_length == -2) + else if (alignment_length == CUDAPOA_KERNEL_NW_ADAPTIVE_STORAGE_FAILED) { if (lane_idx == 0) { @@ -353,6 +459,18 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) } return; } + if (Traceback) + { + if (alignment_length == CUDAPOA_KERNEL_NW_TRACEBACK_BUFFER_FAILED) + { + if (lane_idx == 0) + { + consensus[0] = CUDAPOA_KERNEL_ERROR_ENCOUNTERED; + consensus[1] = static_cast(StatusType::exceeded_maximum_predecessor_distance); + } + return; + } + } if (lane_idx == 0) { @@ -423,18 +541,16 @@ __launch_bounds__(GW_POA_KERNELS_MAX_THREADS_PER_BLOCK) } } -template +template void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, genomeworks::cudapoa::InputDetails* input_details_d, int32_t total_windows, cudaStream_t stream, - genomeworks::cudapoa::AlignmentDetails* alignment_details_d, + genomeworks::cudapoa::AlignmentDetails* alignment_details_d, genomeworks::cudapoa::GraphDetails* graph_details_d, int32_t gap_score, int32_t mismatch_score, int32_t match_score, - bool static_banded, - bool adaptive_banded, uint32_t max_sequences_per_poa, int8_t output_mask, const BatchConfig& batch_size) @@ -453,6 +569,7 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, // unpack alignment details ScoreT* scores = alignment_details_d->scores; + TraceT* traceback = alignment_details_d->traceback; SizeT* alignment_graph = alignment_details_d->alignment_graph; SizeT* alignment_read = alignment_details_d->alignment_read; @@ -478,13 +595,12 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, uint16_t* outgoing_edges_coverage_count = graph_details_d->outgoing_edges_coverage_count; SizeT* node_id_to_msa_pos = graph_details_d->node_id_to_msa_pos; - int32_t nwindows_per_block = CUDAPOA_THREADS_PER_BLOCK / WARP_SIZE; - int32_t nblocks = (static_banded || adaptive_banded) ? total_windows : (total_windows + nwindows_per_block - 1) / nwindows_per_block; - int32_t TPB = (static_banded || adaptive_banded) ? CUDAPOA_BANDED_THREADS_PER_BLOCK : CUDAPOA_THREADS_PER_BLOCK; - int32_t max_nodes_per_graph = batch_size.max_nodes_per_graph; - int32_t matrix_graph_dimension = batch_size.matrix_graph_dimension; - int32_t matrix_seq_dimension = batch_size.matrix_sequence_dimension; - bool msa = output_mask & OutputType::msa; + int32_t nwindows_per_block = CUDAPOA_THREADS_PER_BLOCK / WARP_SIZE; + int32_t nblocks = (batch_size.band_mode != BandMode::full_band) ? total_windows : (total_windows + nwindows_per_block - 1) / nwindows_per_block; + int32_t TPB = (batch_size.band_mode != BandMode::full_band) ? CUDAPOA_BANDED_THREADS_PER_BLOCK : CUDAPOA_THREADS_PER_BLOCK; + int32_t max_nodes_per_graph = batch_size.max_nodes_per_graph; + int32_t matrix_seq_dimension = batch_size.matrix_sequence_dimension; + bool msa = output_mask & OutputType::msa; GW_CU_CHECK_ERR(cudaDeviceSetCacheConfig(cudaFuncCachePreferL1)); @@ -492,9 +608,9 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, if (msa) { - if (static_banded) + if (batch_size.band_mode == BandMode::static_band) { - generatePOAKernel + generatePOAKernel <<>>(consensus_d, sequences_d, base_weights_d, @@ -527,15 +643,14 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, outgoing_edges_coverage, outgoing_edges_coverage_count, max_nodes_per_graph, - matrix_graph_dimension, matrix_seq_dimension, batch_size.max_consensus_size, TPB, batch_size.alignment_band_width); } - else if (adaptive_banded) + else if (batch_size.band_mode == BandMode::adaptive_band) { - generatePOAKernel + generatePOAKernel <<>>(consensus_d, sequences_d, base_weights_d, @@ -568,15 +683,14 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, outgoing_edges_coverage, outgoing_edges_coverage_count, max_nodes_per_graph, - matrix_graph_dimension, matrix_seq_dimension, batch_size.max_consensus_size, TPB, batch_size.alignment_band_width); } - else + else if (batch_size.band_mode == BandMode::static_band_traceback) { - generatePOAKernel + generatePOAKernel <<>>(consensus_d, sequences_d, base_weights_d, @@ -609,18 +723,100 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, outgoing_edges_coverage, outgoing_edges_coverage_count, max_nodes_per_graph, - matrix_graph_dimension, matrix_seq_dimension, batch_size.max_consensus_size, TPB, - batch_size.alignment_band_width); + batch_size.alignment_band_width, + batch_size.max_banded_pred_distance, + traceback); + } + else if (batch_size.band_mode == BandMode::adaptive_band_traceback) + { + generatePOAKernel + <<>>(consensus_d, + sequences_d, + base_weights_d, + sequence_lengths_d, + window_details_d, + total_windows, + scores, + alignment_graph, + alignment_read, + nodes, + incoming_edges, + incoming_edge_count, + outgoing_edges, + outgoing_edge_count, + incoming_edge_w, + sorted_poa, + node_id_to_pos, + node_alignments, + node_alignment_count, + sorted_poa_local_edge_count, + node_marks, + check_aligned_nodes, + nodes_to_visit, + node_coverage_counts, + gap_score, + mismatch_score, + match_score, + max_sequences_per_poa, + sequence_begin_nodes_ids, + outgoing_edges_coverage, + outgoing_edges_coverage_count, + max_nodes_per_graph, + matrix_seq_dimension, + batch_size.max_consensus_size, + TPB, + batch_size.alignment_band_width, + batch_size.max_banded_pred_distance, + traceback); + } + else + { + generatePOAKernel + <<>>(consensus_d, + sequences_d, + base_weights_d, + sequence_lengths_d, + window_details_d, + total_windows, + scores, + alignment_graph, + alignment_read, + nodes, + incoming_edges, + incoming_edge_count, + outgoing_edges, + outgoing_edge_count, + incoming_edge_w, + sorted_poa, + node_id_to_pos, + node_alignments, + node_alignment_count, + sorted_poa_local_edge_count, + node_marks, + check_aligned_nodes, + nodes_to_visit, + node_coverage_counts, + gap_score, + mismatch_score, + match_score, + max_sequences_per_poa, + sequence_begin_nodes_ids, + outgoing_edges_coverage, + outgoing_edges_coverage_count, + max_nodes_per_graph, + matrix_seq_dimension, + batch_size.max_consensus_size, + TPB); } } else { - if (static_banded) + if (batch_size.band_mode == BandMode::static_band) { - generatePOAKernel + generatePOAKernel <<>>(consensus_d, sequences_d, base_weights_d, @@ -653,15 +849,14 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, outgoing_edges_coverage, outgoing_edges_coverage_count, max_nodes_per_graph, - matrix_graph_dimension, matrix_seq_dimension, batch_size.max_consensus_size, TPB, batch_size.alignment_band_width); } - else if (adaptive_banded) + else if (batch_size.band_mode == BandMode::adaptive_band) { - generatePOAKernel + generatePOAKernel <<>>(consensus_d, sequences_d, base_weights_d, @@ -694,15 +889,14 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, outgoing_edges_coverage, outgoing_edges_coverage_count, max_nodes_per_graph, - matrix_graph_dimension, matrix_seq_dimension, batch_size.max_consensus_size, TPB, batch_size.alignment_band_width); } - else + else if (batch_size.band_mode == BandMode::static_band_traceback) { - generatePOAKernel + generatePOAKernel <<>>(consensus_d, sequences_d, base_weights_d, @@ -735,11 +929,93 @@ void generatePOA(genomeworks::cudapoa::OutputDetails* output_details_d, outgoing_edges_coverage, outgoing_edges_coverage_count, max_nodes_per_graph, - matrix_graph_dimension, matrix_seq_dimension, batch_size.max_consensus_size, TPB, - batch_size.alignment_band_width); + batch_size.alignment_band_width, + batch_size.max_banded_pred_distance, + traceback); + } + else if (batch_size.band_mode == BandMode::adaptive_band_traceback) + { + generatePOAKernel + <<>>(consensus_d, + sequences_d, + base_weights_d, + sequence_lengths_d, + window_details_d, + total_windows, + scores, + alignment_graph, + alignment_read, + nodes, + incoming_edges, + incoming_edge_count, + outgoing_edges, + outgoing_edge_count, + incoming_edge_w, + sorted_poa, + node_id_to_pos, + node_alignments, + node_alignment_count, + sorted_poa_local_edge_count, + node_marks, + check_aligned_nodes, + nodes_to_visit, + node_coverage_counts, + gap_score, + mismatch_score, + match_score, + max_sequences_per_poa, + sequence_begin_nodes_ids, + outgoing_edges_coverage, + outgoing_edges_coverage_count, + max_nodes_per_graph, + matrix_seq_dimension, + batch_size.max_consensus_size, + TPB, + batch_size.alignment_band_width, + batch_size.max_banded_pred_distance, + traceback); + } + else + { + generatePOAKernel + <<>>(consensus_d, + sequences_d, + base_weights_d, + sequence_lengths_d, + window_details_d, + total_windows, + scores, + alignment_graph, + alignment_read, + nodes, + incoming_edges, + incoming_edge_count, + outgoing_edges, + outgoing_edge_count, + incoming_edge_w, + sorted_poa, + node_id_to_pos, + node_alignments, + node_alignment_count, + sorted_poa_local_edge_count, + node_marks, + check_aligned_nodes, + nodes_to_visit, + node_coverage_counts, + gap_score, + mismatch_score, + match_score, + max_sequences_per_poa, + sequence_begin_nodes_ids, + outgoing_edges_coverage, + outgoing_edges_coverage_count, + max_nodes_per_graph, + matrix_seq_dimension, + batch_size.max_consensus_size, + TPB); } } GW_CU_CHECK_ERR(cudaPeekAtLastError()); diff --git a/cudapoa/src/cudapoa_limits.hpp b/cudapoa/src/cudapoa_limits.hpp index bbe058561..cf1ffaa0f 100644 --- a/cudapoa/src/cudapoa_limits.hpp +++ b/cudapoa/src/cudapoa_limits.hpp @@ -52,6 +52,12 @@ static bool use32bitSize(const BatchConfig& batch_size) return (max_length > INT16_MAX); } +static bool use16bitTrace(const BatchConfig& batch_size) +{ + //if max_banded_pred_distance exceeds the range represented by int8_t, then int16_t should be used + return (batch_size.max_banded_pred_distance > INT8_MAX); +} + } // namespace cudapoa } // namespace genomeworks } // namespace claraparabricks diff --git a/cudapoa/src/cudapoa_nw.cuh b/cudapoa/src/cudapoa_nw.cuh index a71886209..4ab09ffa1 100644 --- a/cudapoa/src/cudapoa_nw.cuh +++ b/cudapoa/src/cudapoa_nw.cuh @@ -138,8 +138,8 @@ __device__ __forceinline__ * @param[in] read Device buffer with sequence (read) to align * @param[in] read_length Number of bases in read * @param[out] scores Device scratch space that scores alignment matrix score - * @param[out] alignment_graph Device scratch space for backtrace alignment of graph - * @param[out] alignment_read Device scratch space for backtrace alignment of sequence + * @param[out] alignment_graph Device scratch space for traceback alignment of graph + * @param[out] alignment_read Device scratch space for traceback alignment of sequence * @param[in] gap_score Score for inserting gap into alignment * @param[in] mismatch_score Score for finding a mismatch in alignment * @param[in] match_score Score for finding a match in alignment @@ -152,22 +152,22 @@ template __device__ __forceinline__ int32_t - runNeedlemanWunsch(SeqT* nodes, - SizeT* graph, - SizeT* node_id_to_pos, - int32_t graph_count, - uint16_t* incoming_edge_count, - SizeT* incoming_edges, - uint16_t* outgoing_edge_count, - SeqT* read, - int32_t read_length, - ScoreT* scores, - int32_t scores_width, - SizeT* alignment_graph, - SizeT* alignment_read, - int32_t gap_score, - int32_t mismatch_score, - int32_t match_score) + needlemanWunsch(SeqT* nodes, + SizeT* graph, + SizeT* node_id_to_pos, + int32_t graph_count, + uint16_t* incoming_edge_count, + SizeT* incoming_edges, + uint16_t* outgoing_edge_count, + SeqT* read, + int32_t read_length, + ScoreT* scores, + int32_t scores_width, + SizeT* alignment_graph, + SizeT* alignment_read, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score) { static_assert(CPT == 4, "implementation currently supports only 4 cells per thread"); @@ -285,28 +285,11 @@ __device__ __forceinline__ last_score = first_element_prev_score; } - int32_t tscore = max(last_score + gap_score, score.s0); - if (tscore > score.s0) - { - score.s0 = tscore; - loop = true; - } - - tscore = max(score.s0 + gap_score, score.s1); - if (tscore > score.s1) - { - score.s1 = tscore; - loop = true; - } - - tscore = max(score.s1 + gap_score, score.s2); - if (tscore > score.s2) - { - score.s2 = tscore; - loop = true; - } + score.s0 = max(last_score + gap_score, score.s0); + score.s1 = max(score.s0 + gap_score, score.s1); + score.s2 = max(score.s1 + gap_score, score.s2); - tscore = max(score.s2 + gap_score, score.s3); + int32_t tscore = max(score.s2 + gap_score, score.s3); if (tscore > score.s3) { score.s3 = tscore; @@ -353,15 +336,15 @@ __device__ __forceinline__ } } - // Fill in backtrace + // Fill in traceback int32_t prev_i = 0; int32_t prev_j = 0; - // Trace back from maximum score position to generate alignment. - // Trace back is done by re-calculating the score at each cell + // backtrack from maximum score position to generate alignment. + // backtracking is done by re-calculating the score at each cell // along the path to see which preceding cell the move could have - // come from. This seems computaitonally more expensive, but doesn't + // come from. This seems computationally more expensive, but doesn't // require storing any traceback buffer during alignment. int32_t loop_count = 0; while (!(i == 0 && j == 0) && loop_count < static_cast(read_length + graph_count + 2)) @@ -458,7 +441,7 @@ __device__ __forceinline__ if (loop_count >= (read_length + graph_count + 2)) { - aligned_nodes = -1; + aligned_nodes = CUDAPOA_KERNEL_NW_BACKTRACKING_LOOP_FAILED; } #ifdef NW_VERBOSE_PRINT @@ -470,6 +453,8 @@ __device__ __forceinline__ return aligned_nodes; } +// global kernel used in testing, hence uses int16_t for SizeT and ScoreT, +// may need to change if test inputs change to long reads template __global__ void runNeedlemanWunschKernel(uint8_t* nodes, SizeT* graph, @@ -484,27 +469,29 @@ __global__ void runNeedlemanWunschKernel(uint8_t* nodes, int32_t scores_width, SizeT* alignment_graph, SizeT* alignment_read, - int16_t gap_score, - int16_t mismatch_score, - int16_t match_score, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, SizeT* aligned_nodes) { - *aligned_nodes = runNeedlemanWunsch(nodes, - graph, - node_id_to_pos, - graph_count, - incoming_edge_count, - incoming_edges, - outgoing_edge_count, - read, - read_length, - scores, - scores_width, - alignment_graph, - alignment_read, - gap_score, - mismatch_score, - match_score); + static_assert(std::is_same::value, "This function only accepts int16_t as SizeT."); + + *aligned_nodes = needlemanWunsch(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + scores_width, + alignment_graph, + alignment_read, + gap_score, + mismatch_score, + match_score); } // Host function that calls the kernel @@ -522,28 +509,28 @@ void runNW(uint8_t* nodes, int32_t scores_width, SizeT* alignment_graph, SizeT* alignment_read, - int16_t gap_score, - int16_t mismatch_score, - int16_t match_score, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, SizeT* aligned_nodes) { - runNeedlemanWunschKernel<<<1, 64>>>(nodes, - graph, - node_id_to_pos, - graph_count, - incoming_edge_count, - incoming_edges, - outgoing_edge_count, - read, - read_length, - scores, - scores_width, - alignment_graph, - alignment_read, - gap_score, - mismatch_score, - match_score, - aligned_nodes); + runNeedlemanWunschKernel<<<1, CUDAPOA_THREADS_PER_BLOCK>>>(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + scores_width, + alignment_graph, + alignment_read, + gap_score, + mismatch_score, + match_score, + aligned_nodes); GW_CU_CHECK_ERR(cudaPeekAtLastError()); } diff --git a/cudapoa/src/cudapoa_nw_adaptive_banded.cuh b/cudapoa/src/cudapoa_nw_adaptive_banded.cuh deleted file mode 100644 index c0b3570fc..000000000 --- a/cudapoa/src/cudapoa_nw_adaptive_banded.cuh +++ /dev/null @@ -1,557 +0,0 @@ -/* -* Copyright 2019-2020 NVIDIA CORPORATION. -* -* Licensed under the Apache License, Version 2.0 (the "License"); -* you may not use this file except in compliance with the License. -* You may obtain a copy of the License at -* -* http://www.apache.org/licenses/LICENSE-2.0 -* -* Unless required by applicable law or agreed to in writing, software -* distributed under the License is distributed on an "AS IS" BASIS, -* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. -* See the License for the specific language governing permissions and -* limitations under the License. -*/ - -#pragma once - -#include "cudapoa_structs.cuh" - -#include -#include - -#include - -namespace claraparabricks -{ - -namespace genomeworks -{ - -namespace cudapoa -{ - -template -__device__ __forceinline__ ScoreT* get_score_ptr_adaptive(ScoreT* scores, int32_t row, int32_t column, int32_t band_start, int32_t band_width) -{ - column = column == -1 ? 0 : column - band_start; - - int64_t score_index = static_cast(column) + static_cast(row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); - - return &scores[score_index]; -} - -template -__device__ __forceinline__ void set_score_adaptive(ScoreT* scores, int32_t row, int32_t column, int32_t value, int32_t band_start, int32_t band_width) -{ - if (column == -1) - { - column = band_start; - } - else - { - column = column - band_start; - } - - int64_t score_index = static_cast(column) + static_cast(row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); - - scores[score_index] = value; -} - -__device__ __forceinline__ int32_t get_band_start_for_row_adaptive(int32_t row, float gradient, int32_t band_width, int32_t band_shift, int32_t max_column) -{ - - int32_t diagonal_index = int32_t(row * gradient); - int32_t start_pos = max(0, diagonal_index - band_shift); - if (max_column < start_pos + band_width) - { - start_pos = max(0, max_column - band_width + CELLS_PER_THREAD); - } - start_pos = start_pos - (start_pos % CELLS_PER_THREAD); - - return start_pos; -} - -template -__device__ __forceinline__ ScoreT get_score_adaptive(ScoreT* scores, int32_t row, int32_t column, - int32_t band_width, int32_t band_shift, float gradient, - int32_t max_column, const ScoreT min_score_value) -{ - int32_t band_start = get_band_start_for_row_adaptive(row, gradient, band_width, band_shift, max_column); - int32_t band_end = band_start + band_width; - band_end = min(band_end, max_column); - - if ((column > band_end || column < band_start) && column != -1) - { - return min_score_value; - } - else - { - return *get_score_ptr_adaptive(scores, row, column, band_start, band_width); - } -} - -template -__device__ __forceinline__ ScoreT4 get_scores_adaptive(ScoreT* scores, - int32_t row, - int32_t column, - int32_t band_width, - int32_t band_shift, - float gradient, - int32_t max_column, - ScoreT default_value, - int32_t gap_score, - ScoreT4& char_profile) -{ - - // The load instructions typically load data in 4B or 8B chunks. - // If data is 16b (2B), then a 4B load chunk is loaded into register - // and the necessary bits are extracted before returning. This wastes cycles - // as each read of 16b issues a separate load command. - // Instead it is better to load a 4B or 8B chunk into a register - // using a single load inst, and then extracting necessary part of - // of the data using bit arithmatic. Also reduces register count. - - // subtract by CELLS_PER_THREAD to ensure score4_next is not pointing out of the corresponding band bounds - int32_t band_start = get_band_start_for_row_adaptive(row, gradient, band_width, band_shift, max_column); - // subtract by CELLS_PER_THREAD to ensure score4_next is not pointing out of the corresponding band bounds - int32_t band_end = band_start + band_width - CELLS_PER_THREAD; - band_end = min(band_end, max_column); - - if ((column > band_end || column < band_start) && column != -1) - { - return ScoreT4{default_value, default_value, default_value, default_value}; - } - else - { - ScoreT4* pred_scores = (ScoreT4*)get_score_ptr_adaptive(scores, row, column, band_start, band_width); - - // loads 8/16 consecutive bytes (4 ScoreTs) - ScoreT4 score4 = pred_scores[0]; - - // need to load the next chunk of memory as well - ScoreT4 score4_next = pred_scores[1]; - - ScoreT4 score; - - score.s0 = max(score4.s0 + char_profile.s0, - score4.s1 + gap_score); - score.s1 = max(score4.s1 + char_profile.s1, - score4.s2 + gap_score); - score.s2 = max(score4.s2 + char_profile.s2, - score4.s3 + gap_score); - score.s3 = max(score4.s3 + char_profile.s3, - score4_next.s0 + gap_score); - - return score; - } -} - -template -__device__ __forceinline__ void initialize_band_adaptive(ScoreT* scores, int32_t row, int32_t min_score_value, int32_t band_start, int32_t band_width, int32_t lane_idx) -{ - int32_t band_end = band_start + band_width; - - band_start = max(1, band_start); - - set_score_adaptive(scores, row, band_start, min_score_value, band_start, band_width); - if (lane_idx < CUDAPOA_BANDED_MATRIX_RIGHT_PADDING) - { - set_score_adaptive(scores, row, lane_idx + band_end, min_score_value, band_start, band_width); - } -} - -template -__device__ __forceinline__ - int32_t - runNeedlemanWunschAdaptiveBanded(SeqT* nodes, - SizeT* graph, - SizeT* node_id_to_pos, - int32_t graph_count, - uint16_t* incoming_edge_count, - SizeT* incoming_edges, - uint16_t* outgoing_edge_count, - SeqT* read, - int32_t read_length, - ScoreT* scores, - float scores_size, - SizeT* alignment_graph, - SizeT* alignment_read, - int32_t static_band_width, - int32_t gap_score, - int32_t mismatch_score, - int32_t match_score, - int32_t rerun) -{ - // in adaptive bands, there can be cases where multiple rows happen to have a band with start index - // smaller than band-start index of a row above. If min_value is too close to numeric_limits::min(), - // this can cause overflow, therefore min_score_value is selected far enough - const ScoreT min_score_value = numeric_limits::min() / 2; - - int32_t lane_idx = threadIdx.x % WARP_SIZE; - - // Calculate aspect ratio for the scores matrix - float gradient = float(read_length + 1) / float(graph_count + 1); - - int32_t max_column = read_length + 1; - - // Set band-width based on scores matrix aspect ratio - //--------------------------------------------------------- - int32_t band_width = static_band_width; - - if (gradient > 1.1) // ad-hoc rule 1.a - { - // ad-hoc rule 1.b - band_width = max(band_width, cudautils::align(max_column * 0.08 * gradient)); - } - if (gradient < 0.8) // ad-hoc rule 2.a - { - // ad-hoc rule 2.b - band_width = max(band_width, cudautils::align(max_column * 0.1 / gradient)); - } - - // limit band-width for very large reads, ad-hoc rule 3 - ///ToDo add a check for cases where static_band_width > CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH - band_width = min(band_width, CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH); - // band_shift defines distance of band_start from the scores matrix diagonal, ad-hoc rule 4 - int32_t band_shift = band_width / 2; - // rerun code is defined in backtracking loop from previous alignment try - // -3 means backtrace path was too close to the left bound of band - // -4 means backtrace path was too close to the right bound of band - // Therefore we rerun alignment of the same read, but this time with double band-width and band_shift - // further to the left for rerun == -3, and further to the right for rerun == -4. - if (rerun == -3) - { - // ad-hoc rule 5 - band_width *= 2; - band_shift *= 2.5; - } - if (rerun == -4) - { - // ad-hoc rule 6 - band_width *= 2; - band_shift *= 1.5; - } - //--------------------------------------------------------- - - // check required memory and return error if exceeding scores_size - // using float to avoid 64-bit - float required_scores_size = static_cast(graph_count) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); - if (required_scores_size > scores_size) - { - return -2; - } - - // Initialise the horizontal boundary of the score matrix, initialising of the vertical boundary is done within the main for loop - for (int32_t j = lane_idx; j < band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING; j += WARP_SIZE) - { - scores[j] = static_cast(j * gap_score); - } - -#ifdef NW_VERBOSE_PRINT - if (lane_idx == 0) - { - printf("graph %d, read %d\n", graph_count, read_length); - } -#endif - - __syncwarp(); - - // compute vertical and diagonal values in parallel. - for (int32_t graph_pos = 0; graph_pos < graph_count; graph_pos++) - { - int32_t node_id = graph[graph_pos]; - int32_t score_gIdx = graph_pos + 1; - int32_t band_start = get_band_start_for_row_adaptive(score_gIdx, gradient, band_width, band_shift, max_column); - int32_t pred_node_id = incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES]; - - initialize_band_adaptive(scores, score_gIdx, min_score_value, band_start, band_width, lane_idx); - - int32_t first_element_prev_score = 0; - - uint16_t pred_count = 0; - int32_t pred_idx = 0; - - if (lane_idx == 0) - { - int32_t penalty; - pred_count = incoming_edge_count[node_id]; - if (pred_count == 0) - { - set_score_adaptive(scores, score_gIdx, -1, gap_score, band_start, band_width); - } - else - { - pred_idx = node_id_to_pos[pred_node_id] + 1; - if (band_start > CELLS_PER_THREAD && pred_count == 1) - { - first_element_prev_score = min_score_value + gap_score; - } - else - { - penalty = max(min_score_value, get_score_adaptive(scores, pred_idx, -1, band_width, band_shift, gradient, max_column, min_score_value)); - // if pred_num > 1 keep checking to find max score as penalty - for (int32_t p = 0; p < pred_count; p++) - { - pred_node_id = incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]; - int32_t pred_idx_tmp = node_id_to_pos[pred_node_id] + 1; - penalty = max(penalty, get_score_adaptive(scores, pred_idx_tmp, -1, band_width, band_shift, gradient, max_column, min_score_value)); - } - first_element_prev_score = penalty + gap_score; - } - set_score_adaptive(scores, score_gIdx, -1, first_element_prev_score, band_start, band_width); - } - } - pred_count = __shfl_sync(FULL_MASK, pred_count, 0); - pred_idx = __shfl_sync(FULL_MASK, pred_idx, 0); - //------------------------------------------------------------- - - SeqT graph_base = nodes[node_id]; - - for (int32_t read_pos = lane_idx * CELLS_PER_THREAD + band_start; read_pos < band_start + band_width; read_pos += WARP_SIZE * CELLS_PER_THREAD) - { - SeqT4* d_read4 = (SeqT4*)read; - SeqT4 read4 = d_read4[read_pos / CELLS_PER_THREAD]; - - ScoreT4 char_profile; - char_profile.s0 = (graph_base == read4.r0 ? match_score : mismatch_score); - char_profile.s1 = (graph_base == read4.r1 ? match_score : mismatch_score); - char_profile.s2 = (graph_base == read4.r2 ? match_score : mismatch_score); - char_profile.s3 = (graph_base == read4.r3 ? match_score : mismatch_score); - - ScoreT4 score = get_scores_adaptive(scores, pred_idx, read_pos, band_width, band_shift, gradient, max_column, min_score_value, gap_score, char_profile); - - // Perform same score updates as above, but for rest of predecessors. - for (int32_t p = 1; p < pred_count; p++) - { - int32_t pred_idx2 = node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]] + 1; - - ScoreT4 scores_4 = get_scores_adaptive(scores, pred_idx2, read_pos, band_width, band_shift, gradient, max_column, min_score_value, gap_score, char_profile); - - score.s0 = max(score.s0, scores_4.s0); - score.s1 = max(score.s1, scores_4.s1); - score.s2 = max(score.s2, scores_4.s2); - score.s3 = max(score.s3, scores_4.s3); - } - - // While there are changes to the horizontal score values, keep updating the matrix. - // So loop will only run the number of time there are corrections in the matrix. - // The any_sync warp primitive lets us easily check if any of the threads had an update. - bool loop = true; - - while (__any_sync(FULL_MASK, loop)) - { - loop = false; - // Note: computation of s3 depends on s2, s2 depends on s1 and s1 on s0. - // If we reverse the order of computation in this loop from s3 to s0, it will increase - // ILP. However, in longer reads where indels are more frequent, this reverse computations - // results in larger number of iterations. Since if s0 is changed, value of s1, s2 and s3 which - // already have been computed in parallel need to be updated again. - - // The shfl_up lets us grab a value from the lane below. - int32_t last_score = __shfl_up_sync(FULL_MASK, score.s3, 1); - if (lane_idx == 0) - { - last_score = first_element_prev_score; - } - - int32_t tscore = max(last_score + gap_score, score.s0); - if (tscore > score.s0) - { - score.s0 = tscore; - loop = true; - } - - tscore = max(score.s0 + gap_score, score.s1); - if (tscore > score.s1) - { - score.s1 = tscore; - loop = true; - } - - tscore = max(score.s1 + gap_score, score.s2); - if (tscore > score.s2) - { - score.s2 = tscore; - loop = true; - } - - tscore = max(score.s2 + gap_score, score.s3); - if (tscore > score.s3) - { - score.s3 = tscore; - loop = true; - } - } - - // Copy over the last element score of the last lane into a register of first lane - // which can be used to compute the first cell of the next warp. - first_element_prev_score = __shfl_sync(FULL_MASK, score.s3, WARP_SIZE - 1); - - int64_t score_index = static_cast(read_pos + 1 - band_start) + static_cast(score_gIdx) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); - - scores[score_index] = score.s0; - scores[score_index + 1L] = score.s1; - scores[score_index + 2L] = score.s2; - scores[score_index + 3L] = score.s3; - - __syncwarp(); - } - } - - int32_t aligned_nodes = 0; - if (lane_idx == 0) - { - // Find location of the maximum score in the matrix. - int32_t i = 0; - int32_t j = read_length; - int32_t mscore = min_score_value; - - for (int32_t idx = 1; idx <= graph_count; idx++) - { - if (outgoing_edge_count[graph[idx - 1]] == 0) - { - int32_t s = get_score_adaptive(scores, idx, j, band_width, band_shift, gradient, max_column, min_score_value); - if (mscore < s) - { - mscore = s; - i = idx; - } - } - } - - // Fill in backtrace - int32_t prev_i = 0; - int32_t prev_j = 0; - int32_t next_node_id = i > 0 ? graph[i - 1] : 0; - - int32_t loop_count = 0; - while (!(i == 0 && j == 0) && loop_count < static_cast(read_length + graph_count + 2)) - { - loop_count++; - int32_t scores_ij = get_score_adaptive(scores, i, j, band_width, band_shift, gradient, max_column, min_score_value); - bool pred_found = false; - // Check if move is diagonal. - if (i != 0 && j != 0) - { - if (rerun == 0) - { - // check if backtrace gets too close or hits the band limits, if so stop and rerun with extended band-width - // threshold for proximity to band limits works better if defined proportionate to the sequence length - int32_t threshold = max(1, max_column / 1024); // ad-hoc rule 7 - if (j > threshold && j < max_column - threshold) - { - int32_t band_start = get_band_start_for_row_adaptive(i, gradient, band_width, band_shift, max_column); - if (j <= band_start + threshold) // ad-hoc rule 8-a, too close to left bound - { - aligned_nodes = -3; - break; - } - if (j >= (band_start + band_width - threshold)) // ad-hoc rule 8-b, too close to right bound - { - aligned_nodes = -4; - break; - } - } - } - - int32_t node_id = next_node_id; - int32_t match_cost = (nodes[node_id] == read[j - 1] ? match_score : mismatch_score); - - uint16_t pred_count = incoming_edge_count[node_id]; - int32_t pred_i = (pred_count == 0 ? 0 : (node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES]] + 1)); - - if (scores_ij == (get_score_adaptive(scores, pred_i, j - 1, band_width, band_shift, gradient, max_column, min_score_value) + match_cost)) - { - prev_i = pred_i; - prev_j = j - 1; - pred_found = true; - } - - if (!pred_found) - { - for (int32_t p = 1; p < pred_count; p++) - { - pred_i = (node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]] + 1); - - if (scores_ij == (get_score_adaptive(scores, pred_i, j - 1, band_width, band_shift, gradient, max_column, min_score_value) + match_cost)) - { - prev_i = pred_i; - prev_j = j - 1; - pred_found = true; - break; - } - } - } - } - - // Check if move is vertical. - if (!pred_found && i != 0) - { - int32_t node_id = graph[i - 1]; - uint16_t pred_count = incoming_edge_count[node_id]; - int32_t pred_i = (pred_count == 0 ? 0 : node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES]] + 1); - - if (scores_ij == get_score_adaptive(scores, pred_i, j, band_width, band_shift, gradient, max_column, min_score_value) + gap_score) - { - prev_i = pred_i; - prev_j = j; - pred_found = true; - } - - if (!pred_found) - { - for (int32_t p = 1; p < pred_count; p++) - { - pred_i = node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]] + 1; - - if (scores_ij == get_score_adaptive(scores, pred_i, j, band_width, band_shift, gradient, max_column, min_score_value) + gap_score) - { - prev_i = pred_i; - prev_j = j; - pred_found = true; - break; - } - } - } - } - - // Check if move is horizontal. - if (!pred_found && scores_ij == get_score_adaptive(scores, i, j - 1, band_width, band_shift, gradient, max_column, min_score_value) + gap_score) - { - prev_i = i; - prev_j = j - 1; - pred_found = true; - } - - next_node_id = graph[prev_i - 1]; - - alignment_graph[aligned_nodes] = (i == prev_i ? -1 : graph[i - 1]); - alignment_read[aligned_nodes] = (j == prev_j ? -1 : j - 1); - aligned_nodes++; - - i = prev_i; - j = prev_j; - } - - if (loop_count >= (read_length + graph_count + 2)) - { - aligned_nodes = -1; - } - -#ifdef NW_VERBOSE_PRINT - printf("aligned nodes %d, loop count %d\n", aligned_nodes, loop_count); -#endif - } - aligned_nodes = __shfl_sync(FULL_MASK, aligned_nodes, 0); - return aligned_nodes; -} - -} // namespace cudapoa - -} // namespace genomeworks - -} // namespace claraparabricks diff --git a/cudapoa/src/cudapoa_nw_banded.cuh b/cudapoa/src/cudapoa_nw_banded.cuh index adbc5b295..c754e1661 100644 --- a/cudapoa/src/cudapoa_nw_banded.cuh +++ b/cudapoa/src/cudapoa_nw_banded.cuh @@ -32,27 +32,6 @@ namespace genomeworks namespace cudapoa { -__device__ __forceinline__ int32_t get_band_start_for_row(int32_t row_idx, float gradient, int32_t band_width, int32_t max_column) -{ - - int32_t start_pos = int32_t(row_idx * gradient) - band_width / 2; - - start_pos = max(start_pos, 0); - - int32_t end_pos = start_pos + band_width; - - if (end_pos > max_column) - { - start_pos = max_column - band_width + CELLS_PER_THREAD; - }; - - start_pos = max(start_pos, 0); - - start_pos = start_pos - (start_pos % CELLS_PER_THREAD); - - return start_pos; -} - template __device__ __forceinline__ ScoreT* get_score_ptr(ScoreT* scores, int32_t row, int32_t column, int32_t band_start, int32_t band_width) { @@ -61,52 +40,58 @@ __device__ __forceinline__ ScoreT* get_score_ptr(ScoreT* scores, int32_t row, in int64_t score_index = static_cast(column) + static_cast(row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); return &scores[score_index]; -}; +} template -__device__ __forceinline__ void set_score(ScoreT* scores, int32_t row, int32_t column, int32_t value, float gradient, int32_t band_width, int32_t max_column) +__device__ __forceinline__ void set_score(ScoreT* scores, + int32_t row, + int32_t column, + int32_t value, + int32_t band_start, + int32_t band_width) { - int32_t band_start = get_band_start_for_row(row, gradient, band_width, max_column); - - int32_t col_idx; if (column == -1) { - col_idx = band_start; + column = band_start; } else { - col_idx = column - band_start; + column = column - band_start; } - int64_t score_index = static_cast(col_idx) + static_cast(row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + int64_t score_index = static_cast(column) + static_cast(row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + scores[score_index] = value; } -template -__device__ __forceinline__ void initialize_band(ScoreT* scores, int32_t row, int32_t value, float gradient, int32_t band_width, int32_t max_column, int32_t lane_idx) +__device__ __forceinline__ int32_t get_band_start_for_row(int32_t row, float gradient, int32_t band_width, int32_t band_shift, int32_t max_column) { - int32_t band_start = get_band_start_for_row(row, gradient, band_width, max_column); - int32_t band_end = band_start + band_width; - - int32_t initialization_offset = (band_start == 0) ? 1 : band_start; - - set_score(scores, row, initialization_offset, value, gradient, band_width, max_column); - - // note: as long as CUDAPOA_BANDED_MATRIX_RIGHT_PADDING < WARP_SIZE, no need for a for loop - for (int32_t j = lane_idx + band_end; j < band_end + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING; j += WARP_SIZE) + int32_t diagonal_index = int32_t(row * gradient); + int32_t start_pos = max(0, diagonal_index - band_shift); + if (max_column < start_pos + band_width) { - set_score(scores, row, j, value, gradient, band_width, max_column); + start_pos = max(0, max_column - band_width + CUDAPOA_CELLS_PER_THREAD); } + start_pos = start_pos - (start_pos % CUDAPOA_CELLS_PER_THREAD); + + return start_pos; } template -__device__ __forceinline__ ScoreT get_score(ScoreT* scores, int32_t row, int32_t column, float gradient, int32_t band_width, int32_t max_column, const ScoreT min_score_value) +__device__ __forceinline__ ScoreT get_score(ScoreT* scores, + int32_t row, + int32_t column, + int32_t band_width, + int32_t band_shift, + float gradient, + int32_t max_column, + const ScoreT min_score_value) { - int32_t band_start = get_band_start_for_row(row, gradient, band_width, max_column); + int32_t band_start = get_band_start_for_row(row, gradient, band_width, band_shift, max_column); int32_t band_end = band_start + band_width; band_end = min(band_end, max_column); - if (((column > band_end) || (column < band_start)) && column != -1) + if ((column > band_end || column < band_start) && column != -1) { return min_score_value; } @@ -118,16 +103,16 @@ __device__ __forceinline__ ScoreT get_score(ScoreT* scores, int32_t row, int32_t template __device__ __forceinline__ ScoreT4 get_scores(ScoreT* scores, - int32_t node, - int32_t read_pos, - float gradient, + int32_t row, + int32_t column, int32_t band_width, + int32_t band_shift, + float gradient, int32_t max_column, ScoreT default_value, int32_t gap_score, ScoreT4& char_profile) { - // The load instructions typically load data in 4B or 8B chunks. // If data is 16b (2B), then a 4B load chunk is loaded into register // and the necessary bits are extracted before returning. This wastes cycles @@ -136,20 +121,20 @@ __device__ __forceinline__ ScoreT4 get_scores(ScoreT* scores, // using a single load inst, and then extracting necessary part of // of the data using bit arithmatic. Also reduces register count. - int32_t band_start = get_band_start_for_row(node, gradient, band_width, max_column); - + int32_t band_start = get_band_start_for_row(row, gradient, band_width, band_shift, max_column); // subtract by CELLS_PER_THREAD to ensure score4_next is not pointing out of the corresponding band bounds - int32_t band_end = static_cast(band_start + band_width - CELLS_PER_THREAD); + int32_t band_end = band_start + band_width - CUDAPOA_CELLS_PER_THREAD; + band_end = min(band_end, max_column); - if ((read_pos > band_end || read_pos < band_start) && read_pos != -1) + if ((column > band_end || column < band_start) && column != -1) { return ScoreT4{default_value, default_value, default_value, default_value}; } else { - ScoreT4* pred_scores = (ScoreT4*)get_score_ptr(scores, node, read_pos, band_start, band_width); + ScoreT4* pred_scores = (ScoreT4*)get_score_ptr(scores, row, column, band_start, band_width); - // loads 8/16 consecutive bytes (4 ScoreT) + // loads 8/16 consecutive bytes (4 ScoreTs) ScoreT4 score4 = pred_scores[0]; // need to load the next chunk of memory as well @@ -170,49 +155,128 @@ __device__ __forceinline__ ScoreT4 get_scores(ScoreT* scores, } } +template +__device__ __forceinline__ void initialize_band(ScoreT* scores, + int32_t row, + int32_t min_score_value, + int32_t band_start, + int32_t band_width, + int32_t lane_idx) +{ + int32_t band_end = band_start + band_width; + + band_start = max(1, band_start); + + set_score(scores, row, band_start, min_score_value, band_start, band_width); + if (lane_idx < CUDAPOA_BANDED_MATRIX_RIGHT_PADDING) + { + set_score(scores, row, lane_idx + band_end, min_score_value, band_start, band_width); + } +} + template + typename SizeT, + bool Adaptive = true> __device__ __forceinline__ int32_t - runNeedlemanWunschBanded(SeqT* nodes, - SizeT* graph, - SizeT* node_id_to_pos, - int32_t graph_count, - uint16_t* incoming_edge_count, - SizeT* incoming_edges, - uint16_t* outgoing_edge_count, - SeqT* read, - int32_t read_length, - ScoreT* scores, - SizeT* alignment_graph, - SizeT* alignment_read, - int32_t band_width, - int32_t gap_score, - int32_t mismatch_score, - int32_t match_score) + needlemanWunschBanded(SeqT* nodes, + SizeT* graph, + SizeT* node_id_to_pos, + int32_t graph_count, + uint16_t* incoming_edge_count, + SizeT* incoming_edges, + uint16_t* outgoing_edge_count, + SeqT* read, + int32_t read_length, + ScoreT* scores, + float max_buffer_size, + SizeT* alignment_graph, + SizeT* alignment_read, + int32_t band_width, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, + int32_t rerun) { - - const ScoreT min_score_value = 2 * abs(min(min(gap_score, mismatch_score), -match_score) - 1) + numeric_limits::min(); + const ScoreT min_score_value = numeric_limits::min() / 2; int32_t lane_idx = threadIdx.x % WARP_SIZE; - //Calculate gradient for the scores matrix + // Calculate aspect ratio for the scores matrix float gradient = float(read_length + 1) / float(graph_count + 1); int32_t max_column = read_length + 1; - // Initialise the horizontal boundary of the score matrix + + // Set band-width based on scores matrix aspect ratio + //--------------------------------------------------------- + if (Adaptive) + { + if (gradient > 1.1) // ad-hoc rule 1.a + { + // ad-hoc rule 1.b + band_width = max(band_width, cudautils::align(max_column * 0.08 * gradient)); + } + if (gradient < 0.8) // ad-hoc rule 2.a + { + // ad-hoc rule 2.b + band_width = max(band_width, cudautils::align(max_column * 0.1 / gradient)); + } + + // limit band-width for very large reads, ad-hoc rule 3 + band_width = min(band_width, CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH); + + if (band_width == CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH && rerun != 0) + { + // already we have tried with maximum allowed band-width, rerun won't help + return rerun; + } + } + + // band_shift defines distance of band_start from the scores matrix diagonal, ad-hoc rule 4 + int32_t band_shift = band_width / 2; + + if (Adaptive) + { + // rerun code is defined in backtracking loop from previous alignment try + // SHIFT_ADAPTIVE_BAND_TO_LEFT means traceback path was too close to the left bound of band + // SHIFT_ADAPTIVE_BAND_TO_RIGHT means traceback path was too close to the right bound of band + // Therefore we rerun alignment of the same read, but this time with double band-width and band_shift further to + // the left for rerun == SHIFT_ADAPTIVE_BAND_TO_LEFT, and further to the right for rerun == SHIFT_ADAPTIVE_BAND_TO_RIGHT. + if (rerun == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_LEFT && band_width <= CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH / 2) + { + // ad-hoc rule 5 + band_width *= 2; + band_shift *= 2.5; + } + if (rerun == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_RIGHT && band_width <= CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH / 2) + { + // ad-hoc rule 6 + band_width *= 2; + band_shift *= 1.5; + } + // check required memory and return error if exceeding max_buffer_size + // using float to avoid 64-bit + float required_buffer_size = static_cast(graph_count) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + if (required_buffer_size > max_buffer_size) + { + return CUDAPOA_KERNEL_NW_ADAPTIVE_STORAGE_FAILED; + } + } + //--------------------------------------------------------- + + // Initialise the horizontal boundary of the score matrix, initialising of the vertical boundary is done within the main for loop for (int32_t j = lane_idx; j < band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING; j += WARP_SIZE) { - set_score(scores, 0, j, j * gap_score, gradient, band_width, max_column); + scores[j] = static_cast(j * gap_score); } +#ifdef NW_VERBOSE_PRINT if (lane_idx == 0) { -#ifdef NW_VERBOSE_PRINT printf("graph %d, read %d\n", graph_count, read_length); -#endif } +#endif __syncwarp(); @@ -221,10 +285,10 @@ __device__ __forceinline__ { int32_t node_id = graph[graph_pos]; int32_t score_gIdx = graph_pos + 1; - int32_t band_start = get_band_start_for_row(score_gIdx, gradient, band_width, max_column); + int32_t band_start = get_band_start_for_row(score_gIdx, gradient, band_width, band_shift, max_column); int32_t pred_node_id = incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES]; - initialize_band(scores, score_gIdx, min_score_value, gradient, band_width, max_column, lane_idx); + initialize_band(scores, score_gIdx, min_score_value, band_start, band_width, lane_idx); int32_t first_element_prev_score = 0; uint16_t pred_count = 0; @@ -232,33 +296,32 @@ __device__ __forceinline__ if (lane_idx == 0) { - // Initialise the vertical boundary of the score matrix int32_t penalty; pred_count = incoming_edge_count[node_id]; if (pred_count == 0) { - set_score(scores, score_gIdx, -1, gap_score, gradient, band_width, max_column); + set_score(scores, score_gIdx, -1, gap_score, band_start, band_width); } else { pred_idx = node_id_to_pos[pred_node_id] + 1; - if (band_start > CELLS_PER_THREAD && pred_count == 1) + if (band_start > CUDAPOA_CELLS_PER_THREAD && pred_count == 1) { first_element_prev_score = min_score_value + gap_score; } else { - penalty = max(min_score_value, get_score(scores, pred_idx, -1, gradient, band_width, max_column, min_score_value)); + penalty = max(min_score_value, get_score(scores, pred_idx, -1, band_width, band_shift, gradient, max_column, min_score_value)); // if pred_num > 1 keep checking to find max score as penalty for (int32_t p = 0; p < pred_count; p++) { pred_node_id = incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]; int32_t pred_idx_tmp = node_id_to_pos[pred_node_id] + 1; - penalty = max(penalty, get_score(scores, pred_idx_tmp, -1, gradient, band_width, max_column, min_score_value)); + penalty = max(penalty, get_score(scores, pred_idx_tmp, -1, band_width, band_shift, gradient, max_column, min_score_value)); } first_element_prev_score = penalty + gap_score; } - set_score(scores, score_gIdx, -1, first_element_prev_score, gradient, band_width, max_column); + set_score(scores, score_gIdx, -1, first_element_prev_score, band_start, band_width); } } pred_count = __shfl_sync(FULL_MASK, pred_count, 0); @@ -267,10 +330,10 @@ __device__ __forceinline__ SeqT graph_base = nodes[node_id]; - for (int32_t read_pos = lane_idx * CELLS_PER_THREAD + band_start; read_pos < band_start + band_width; read_pos += CUDAPOA_MIN_BAND_WIDTH) + for (int32_t read_pos = lane_idx * CUDAPOA_CELLS_PER_THREAD + band_start; read_pos < band_start + band_width; read_pos += WARP_SIZE * CUDAPOA_CELLS_PER_THREAD) { SeqT4* d_read4 = (SeqT4*)read; - SeqT4 read4 = d_read4[read_pos / CELLS_PER_THREAD]; + SeqT4 read4 = d_read4[read_pos / CUDAPOA_CELLS_PER_THREAD]; ScoreT4 char_profile; char_profile.s0 = (graph_base == read4.r0 ? match_score : mismatch_score); @@ -278,14 +341,14 @@ __device__ __forceinline__ char_profile.s2 = (graph_base == read4.r2 ? match_score : mismatch_score); char_profile.s3 = (graph_base == read4.r3 ? match_score : mismatch_score); - ScoreT4 score = get_scores(scores, pred_idx, read_pos, gradient, band_width, max_column, min_score_value, gap_score, char_profile); + ScoreT4 score = get_scores(scores, pred_idx, read_pos, band_width, band_shift, gradient, max_column, min_score_value, gap_score, char_profile); // Perform same score updates as above, but for rest of predecessors. for (int32_t p = 1; p < pred_count; p++) { int32_t pred_idx2 = node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]] + 1; - ScoreT4 scores_4 = get_scores(scores, pred_idx2, read_pos, gradient, band_width, max_column, min_score_value, gap_score, char_profile); + ScoreT4 scores_4 = get_scores(scores, pred_idx2, read_pos, band_width, band_shift, gradient, max_column, min_score_value, gap_score, char_profile); score.s0 = max(score.s0, scores_4.s0); score.s1 = max(score.s1, scores_4.s1); @@ -314,28 +377,11 @@ __device__ __forceinline__ last_score = first_element_prev_score; } - int32_t tscore = max(last_score + gap_score, score.s0); - if (tscore > score.s0) - { - score.s0 = tscore; - loop = true; - } - - tscore = max(score.s0 + gap_score, score.s1); - if (tscore > score.s1) - { - score.s1 = tscore; - loop = true; - } + score.s0 = max(last_score + gap_score, score.s0); + score.s1 = max(score.s0 + gap_score, score.s1); + score.s2 = max(score.s1 + gap_score, score.s2); - tscore = max(score.s1 + gap_score, score.s2); - if (tscore > score.s2) - { - score.s2 = tscore; - loop = true; - } - - tscore = max(score.s2 + gap_score, score.s3); + int32_t tscore = max(score.s2 + gap_score, score.s3); if (tscore > score.s3) { score.s3 = tscore; @@ -370,7 +416,7 @@ __device__ __forceinline__ { if (outgoing_edge_count[graph[idx - 1]] == 0) { - int32_t s = get_score(scores, idx, j, gradient, band_width, max_column, min_score_value); + int32_t s = get_score(scores, idx, j, band_width, band_shift, gradient, max_column, min_score_value); if (mscore < s) { mscore = s; @@ -379,7 +425,7 @@ __device__ __forceinline__ } } - // Fill in backtrace + // Fill in traceback int32_t prev_i = 0; int32_t prev_j = 0; int32_t next_node_id = i > 0 ? graph[i - 1] : 0; @@ -388,19 +434,43 @@ __device__ __forceinline__ while (!(i == 0 && j == 0) && loop_count < static_cast(read_length + graph_count + 2)) { loop_count++; - int32_t scores_ij = get_score(scores, i, j, gradient, band_width, max_column, min_score_value); + int32_t scores_ij = get_score(scores, i, j, band_width, band_shift, gradient, max_column, min_score_value); bool pred_found = false; // Check if move is diagonal. if (i != 0 && j != 0) { + if (Adaptive) + { + // no need to request rerun if (a) it's not the first run, (b) band_width == CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH already + if (rerun == 0 && band_width < CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH) + { + // check if traceback gets too close or hits the band limits, if so stop and rerun with extended band-width + // threshold for proximity to band limits works better if defined proportionate to the sequence length + int32_t threshold = max(1, max_column / 1024); // ad-hoc rule 7 + if (j > threshold && j < max_column - threshold) + { + int32_t band_start = get_band_start_for_row(i, gradient, band_width, band_shift, max_column); + if (j <= band_start + threshold) // ad-hoc rule 8-a, too close to left bound + { + aligned_nodes = CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_LEFT; + break; + } + if (j >= (band_start + band_width - threshold)) // ad-hoc rule 8-b, too close to right bound + { + aligned_nodes = CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_RIGHT; + break; + } + } + } + } - int32_t node_id = next_node_id; + int32_t node_id = next_node_id; + int32_t match_cost = (nodes[node_id] == read[j - 1] ? match_score : mismatch_score); - int32_t match_cost = (nodes[node_id] == read[j - 1] ? match_score : mismatch_score); uint16_t pred_count = incoming_edge_count[node_id]; int32_t pred_i = (pred_count == 0 ? 0 : (node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES]] + 1)); - if (scores_ij == (get_score(scores, pred_i, j - 1, gradient, band_width, max_column, min_score_value) + match_cost)) + if (scores_ij == (get_score(scores, pred_i, j - 1, band_width, band_shift, gradient, max_column, min_score_value) + match_cost)) { prev_i = pred_i; prev_j = j - 1; @@ -413,7 +483,7 @@ __device__ __forceinline__ { pred_i = (node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]] + 1); - if (scores_ij == (get_score(scores, pred_i, j - 1, gradient, band_width, max_column, min_score_value) + match_cost)) + if (scores_ij == (get_score(scores, pred_i, j - 1, band_width, band_shift, gradient, max_column, min_score_value) + match_cost)) { prev_i = pred_i; prev_j = j - 1; @@ -431,7 +501,7 @@ __device__ __forceinline__ uint16_t pred_count = incoming_edge_count[node_id]; int32_t pred_i = (pred_count == 0 ? 0 : node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES]] + 1); - if (scores_ij == get_score(scores, pred_i, j, gradient, band_width, max_column, min_score_value) + gap_score) + if (scores_ij == get_score(scores, pred_i, j, band_width, band_shift, gradient, max_column, min_score_value) + gap_score) { prev_i = pred_i; prev_j = j; @@ -444,7 +514,7 @@ __device__ __forceinline__ { pred_i = node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]] + 1; - if (scores_ij == get_score(scores, pred_i, j, gradient, band_width, max_column, min_score_value) + gap_score) + if (scores_ij == get_score(scores, pred_i, j, band_width, band_shift, gradient, max_column, min_score_value) + gap_score) { prev_i = pred_i; prev_j = j; @@ -456,7 +526,7 @@ __device__ __forceinline__ } // Check if move is horizontal. - if (!pred_found && scores_ij == get_score(scores, i, j - 1, gradient, band_width, max_column, min_score_value) + gap_score) + if (!pred_found && scores_ij == get_score(scores, i, j - 1, band_width, band_shift, gradient, max_column, min_score_value) + gap_score) { prev_i = i; prev_j = j - 1; @@ -475,7 +545,7 @@ __device__ __forceinline__ if (loop_count >= (read_length + graph_count + 2)) { - aligned_nodes = -1; + aligned_nodes = CUDAPOA_KERNEL_NW_BACKTRACKING_LOOP_FAILED; } #ifdef NW_VERBOSE_PRINT @@ -486,6 +556,124 @@ __device__ __forceinline__ return aligned_nodes; } +// global kernel used in testing, hence uses int16_t for SizeT and ScoreT, +// may need to change if test inputs change to long reads +template +__global__ void runNeedlemanWunschBandedKernel(uint8_t* nodes, + SizeT* graph, + SizeT* node_id_to_pos, + int32_t graph_count, + uint16_t* incoming_edge_count, + SizeT* incoming_edges, + uint16_t* outgoing_edge_count, + uint8_t* read, + int32_t read_length, + int16_t* scores, + int32_t scores_width, + int32_t max_nodes_per_graph, + SizeT* alignment_graph, + SizeT* alignment_read, + int32_t band_width, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, + SizeT* aligned_nodes) +{ + static_assert(std::is_same::value, "This function only accepts int16_t as SizeT."); + + float banded_buffer_size = static_cast(max_nodes_per_graph) * static_cast(scores_width); + + *aligned_nodes = needlemanWunschBanded(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + banded_buffer_size, + alignment_graph, + alignment_read, + band_width, + gap_score, + mismatch_score, + match_score, + 0); +} + +// Host function that calls the kernel +template +void runNWbanded(uint8_t* nodes, + SizeT* graph, + SizeT* node_id_to_pos, + int32_t graph_count, + uint16_t* incoming_edge_count, + SizeT* incoming_edges, + uint16_t* outgoing_edge_count, + uint8_t* read, + int32_t read_length, + int16_t* scores, + int32_t scores_width, + int32_t max_nodes_per_graph, + SizeT* alignment_graph, + SizeT* alignment_read, + int32_t band_width, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, + SizeT* aligned_nodes, + bool adaptive) +{ + if (adaptive) + { + runNeedlemanWunschBandedKernel<<<1, CUDAPOA_BANDED_THREADS_PER_BLOCK>>>(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + scores_width, + max_nodes_per_graph, + alignment_graph, + alignment_read, + band_width, + gap_score, + mismatch_score, + match_score, + aligned_nodes); + } + else + { + runNeedlemanWunschBandedKernel<<<1, CUDAPOA_BANDED_THREADS_PER_BLOCK>>>(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + scores_width, + max_nodes_per_graph, + alignment_graph, + alignment_read, + band_width, + gap_score, + mismatch_score, + match_score, + aligned_nodes); + } + + GW_CU_CHECK_ERR(cudaPeekAtLastError()); +} + } // namespace cudapoa } // namespace genomeworks diff --git a/cudapoa/src/cudapoa_nw_tb_banded.cuh b/cudapoa/src/cudapoa_nw_tb_banded.cuh new file mode 100644 index 000000000..38ca64b0b --- /dev/null +++ b/cudapoa/src/cudapoa_nw_tb_banded.cuh @@ -0,0 +1,779 @@ +/* +* Copyright 2019-2020 NVIDIA CORPORATION. +* +* Licensed under the Apache License, Version 2.0 (the "License"); +* you may not use this file except in compliance with the License. +* You may obtain a copy of the License at +* +* http://www.apache.org/licenses/LICENSE-2.0 +* +* Unless required by applicable law or agreed to in writing, software +* distributed under the License is distributed on an "AS IS" BASIS, +* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +* See the License for the specific language governing permissions and +* limitations under the License. +*/ + +#pragma once + +#include "cudapoa_structs.cuh" + +#include +#include + +#include + +namespace claraparabricks +{ + +namespace genomeworks +{ + +namespace cudapoa +{ + +template +__device__ __forceinline__ ScoreT* get_score_ptr_tb(ScoreT* scores, int32_t score_row, int32_t column, int32_t band_start, int32_t band_width) +{ + column = column == -1 ? 0 : column - band_start; + + int64_t score_index = static_cast(column) + + static_cast(score_row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + + return &scores[score_index]; +} + +template +__device__ __forceinline__ void set_score_tb(ScoreT* scores, + int32_t row, + int32_t column, + int32_t score_matrix_height, + int32_t value, + int32_t band_start, + int32_t band_width) +{ + int32_t col_idx; + if (column == -1) + { + col_idx = band_start; + } + else + { + col_idx = column - band_start; + } + // in NW with traceback buffer, score matrix is stored partially, hence row is mapped to [0, score_matrix_height) span + row = row % score_matrix_height; + int64_t score_index = static_cast(col_idx) + + static_cast(row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + scores[score_index] = value; +} + +__device__ __forceinline__ int32_t get_band_start_for_row_tb(int32_t row, float gradient, int32_t band_width, int32_t band_shift, int32_t max_column) +{ + int32_t diagonal_index = int32_t(row * gradient); + int32_t start_pos = max(0, diagonal_index - band_shift); + if (max_column < start_pos + band_width) + { + start_pos = max(0, max_column - band_width + CUDAPOA_CELLS_PER_THREAD); + } + start_pos = start_pos - (start_pos % CUDAPOA_CELLS_PER_THREAD); + + return start_pos; +} + +template +__device__ __forceinline__ void initialize_band_tb(ScoreT* scores, + int32_t row, + int32_t score_matrix_height, + int32_t min_score_value, + int32_t band_start, + int32_t band_width, + int32_t lane_idx) +{ + int32_t band_end = band_start + band_width; + + band_start = max(1, band_start); + + set_score_tb(scores, row, band_start, score_matrix_height, min_score_value, band_start, band_width); + + // note: as long as CUDAPOA_BANDED_MATRIX_RIGHT_PADDING < WARP_SIZE, no need for a for loop + for (int32_t j = lane_idx + band_end; j < band_end + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING; j += WARP_SIZE) + { + set_score_tb(scores, row, j, score_matrix_height, min_score_value, band_start, band_width); + } +} + +template +__device__ __forceinline__ TraceT get_trace(TraceT* traceback, int32_t row, int32_t column, int32_t band_start, int32_t band_width) +{ + int64_t trace_index = static_cast(column - band_start) + + static_cast(row) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + return traceback[trace_index]; +} + +template +__device__ __forceinline__ ScoreT get_score_tb(ScoreT* scores, + int32_t row, + int32_t column, + int32_t score_matrix_height, + int32_t band_width, + int32_t band_shift, + float gradient, + int32_t max_column, + const ScoreT min_score_value) +{ + int32_t band_start = get_band_start_for_row_tb(row, gradient, band_width, band_shift, max_column); + int32_t band_end = band_start + band_width; + band_end = min(band_end, max_column); + + if (((column > band_end) || (column < band_start)) && column != -1) + { + return min_score_value; + } + else + { + // row is mapped to [0, score_matrix_height) span + return *get_score_ptr_tb(scores, row % score_matrix_height, column, band_start, band_width); + } +} + +template +__device__ __forceinline__ void get_scores_tb(ScoreT* scores, + int32_t pred_node, + int32_t current_node, + int32_t column, + int32_t score_matrix_height, + int32_t band_width, + int32_t band_shift, + float gradient, + int32_t max_column, + int32_t gap_score, + int32_t match_score, + int32_t mismatch_score, + SeqT4 read4, + SeqT graph_base, + ScoreT4& score, + TraceT4& trace) +{ + // The load instructions typically load data in 4B or 8B chunks. + // If data is 16b (2B), then a 4B load chunk is loaded into register + // and the necessary bits are extracted before returning. This wastes cycles + // as each read of 16b issues a separate load command. + // Instead it is better to load a 4B or 8B chunk into a register + // using a single load inst, and then extracting necessary part of + // of the data using bit arithmetic. Also reduces register count. + + int32_t band_start = get_band_start_for_row_tb(pred_node, gradient, band_width, band_shift, max_column); + + // subtract by CELLS_PER_THREAD to ensure score4_next is not pointing out of the corresponding band bounds + int32_t band_end = band_start + band_width - CUDAPOA_CELLS_PER_THREAD; + band_end = min(band_end, max_column); + + if ((column > band_end || column < band_start) && column != -1) + { + return; + } + else + { + // row is mapped to [0, score_matrix_height) span + ScoreT4* pred_scores = (ScoreT4*)get_score_ptr_tb(scores, pred_node % score_matrix_height, column, band_start, band_width); + + // loads 8/16 consecutive bytes (4 ScoreTs) + ScoreT4 score4 = pred_scores[0]; + + // need to load the next chunk of memory as well + ScoreT4 score4_next = pred_scores[1]; + + int32_t char_profile = (graph_base == read4.r0 ? match_score : mismatch_score); + + // if trace is diogonal, its value is positive and if vertical, negative + // update score.s0, trace.t0 ---------- + if ((score4.s0 + char_profile) >= (score4.s1 + gap_score)) + { + if ((score4.s0 + char_profile) > score.s0) + { + score.s0 = score4.s0 + char_profile; + trace.t0 = current_node - pred_node; + } + } + else + { + if ((score4.s1 + gap_score) > score.s0) + { + score.s0 = score4.s1 + gap_score; + trace.t0 = -(current_node - pred_node); + } + } + // update score.s1, trace.t1 ---------- + char_profile = (graph_base == read4.r1 ? match_score : mismatch_score); + if ((score4.s1 + char_profile) >= (score4.s2 + gap_score)) + { + if ((score4.s1 + char_profile) > score.s1) + { + score.s1 = score4.s1 + char_profile; + trace.t1 = current_node - pred_node; + } + } + else + { + if ((score4.s2 + gap_score) > score.s1) + { + score.s1 = score4.s2 + gap_score; + trace.t1 = -(current_node - pred_node); + } + } + // update score.s2, trace.t2 ---------- + char_profile = (graph_base == read4.r2 ? match_score : mismatch_score); + if ((score4.s2 + char_profile) >= (score4.s3 + gap_score)) + { + if ((score4.s2 + char_profile) > score.s2) + { + score.s2 = score4.s2 + char_profile; + trace.t2 = current_node - pred_node; + } + } + else + { + if ((score4.s3 + gap_score) > score.s2) + { + score.s2 = score4.s3 + gap_score; + trace.t2 = -(current_node - pred_node); + } + } + // update score.s3, trace.t3 ---------- + char_profile = (graph_base == read4.r3 ? match_score : mismatch_score); + if ((score4.s3 + char_profile) >= (score4_next.s0 + gap_score)) + { + if ((score4.s3 + char_profile) > score.s3) + { + score.s3 = score4.s3 + char_profile; + trace.t3 = current_node - pred_node; + } + } + else + { + if ((score4_next.s0 + gap_score) > score.s3) + { + score.s3 = score4_next.s0 + gap_score; + trace.t3 = -(current_node - pred_node); + } + } + } +} + +template +__device__ __forceinline__ + int32_t + needlemanWunschBandedTraceback(SeqT* nodes, + SizeT* graph, + SizeT* node_id_to_pos, + int32_t graph_count, + uint16_t* incoming_edge_count, + SizeT* incoming_edges, + uint16_t* outgoing_edge_count, + SeqT* read, + int32_t read_length, + ScoreT* scores, + TraceT* traceback, + float max_buffer_size, + SizeT* alignment_graph, + SizeT* alignment_read, + int32_t band_width, + int32_t score_matrix_height, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, + int32_t rerun) +{ + const ScoreT min_score_value = numeric_limits::min() / 2; + + int32_t lane_idx = threadIdx.x % WARP_SIZE; + + //Calculate aspect ratio for the scores matrix + float gradient = float(read_length + 1) / float(graph_count + 1); + + int32_t max_column = read_length + 1; + + // Set band-width based on scores matrix aspect ratio + //--------------------------------------------------------- + // band_shift defines distance of band_start from the scores matrix diagonal, ad-hoc rule 4 + int32_t band_shift = band_width / 2; + + if (Adaptive) + { + // rerun code is defined in backtracking loop from previous alignment try + // SHIFT_ADAPTIVE_BAND_TO_LEFT means traceback path was too close to the left bound of band + // SHIFT_ADAPTIVE_BAND_TO_RIGHT means traceback path was too close to the right bound of band + // Therefore we rerun alignment of the same read, but this time with double band-width and band_shift further to + // the left for rerun == SHIFT_ADAPTIVE_BAND_TO_LEFT, and further to the right for rerun == SHIFT_ADAPTIVE_BAND_TO_RIGHT. + if (rerun == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_LEFT && band_width <= CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH / 2) + { + // ad-hoc rule 5 + band_width *= 2; + band_shift *= 2.5; + } + if (rerun == CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_RIGHT && band_width <= CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH / 2) + { + // ad-hoc rule 6 + band_width *= 2; + band_shift *= 1.5; + } + // check required memory and return error if exceeding max_buffer_size + // using float to avoid 64-bit + float required_buffer_size = static_cast(graph_count) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + if (required_buffer_size > max_buffer_size) + { + return CUDAPOA_KERNEL_NW_ADAPTIVE_STORAGE_FAILED; + } + } + //--------------------------------------------------------- + + // Initialise the horizontal boundary of the score matrix, initialising of the vertical boundary is done within the main for loop + for (int32_t j = lane_idx; j < band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING; j += WARP_SIZE) + { + set_score_tb(scores, 0, j, score_matrix_height, j * gap_score, 0, band_width); + } + + if (lane_idx == 0) + { +#ifdef NW_VERBOSE_PRINT + printf("graph %d, read %d\n", graph_count, read_length); +#endif + } + + __syncwarp(); + + // compute vertical and diagonal values in parallel. + for (int32_t graph_pos = 0; graph_pos < graph_count; graph_pos++) + { + int32_t node_id = graph[graph_pos]; + int32_t score_gIdx = graph_pos + 1; + int32_t band_start = get_band_start_for_row_tb(score_gIdx, gradient, band_width, band_shift, max_column); + int32_t pred_node_id = incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES]; + + initialize_band_tb(scores, score_gIdx, score_matrix_height, min_score_value, band_start, band_width, lane_idx); + + int32_t first_element_prev_score = 0; + uint16_t pred_count = 0; + int32_t pred_idx = 0; + + if (lane_idx == 0) + { + // Initialise the vertical boundary of the score matrix + int32_t penalty; + pred_count = incoming_edge_count[node_id]; + if (pred_count == 0) + { + // row is mapped to [0, score_matrix_height) span + int64_t index = static_cast(score_gIdx % score_matrix_height) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + scores[index] = gap_score; + index = static_cast(score_gIdx) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + traceback[index] = -score_gIdx; + } + else + { + int64_t index = static_cast(score_gIdx) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + pred_idx = node_id_to_pos[pred_node_id] + 1; + // only predecessors that are less than score_matrix_height distant can be taken into account + if ((graph_pos - pred_idx) < score_matrix_height) + { + // fill in first column of traceback buffer + traceback[index] = -(score_gIdx - pred_idx); + + if (band_start > CUDAPOA_CELLS_PER_THREAD && pred_count == 1) + { + first_element_prev_score = min_score_value + gap_score; + } + else + { + penalty = max(min_score_value, + get_score_tb(scores, pred_idx, -1, score_matrix_height, band_width, band_shift, gradient, max_column, min_score_value)); + // if pred_num > 1 keep checking to find max score as penalty + for (int32_t p = 1; p < pred_count; p++) + { + pred_node_id = incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]; + int32_t pred_idx_tmp = node_id_to_pos[pred_node_id] + 1; + // only predecessors that are less than score_matrix_height distant can be taken into account + if ((score_gIdx - pred_idx_tmp) < score_matrix_height) + { + int32_t trace_tmp = -(score_gIdx - pred_idx_tmp); + int32_t score_tmp = get_score_tb(scores, pred_idx_tmp, -1, score_matrix_height, band_width, band_shift, + gradient, max_column, min_score_value); + if (penalty < score_tmp) + { + penalty = score_tmp; + traceback[index] = trace_tmp; + } + } + } + first_element_prev_score = penalty + gap_score; + set_score_tb(scores, score_gIdx, -1, score_matrix_height, first_element_prev_score, band_start, band_width); + } + } + else + { + penalty = min_score_value; + // look for a predecessor which is within score_matrix_height limit + for (int32_t p = 1; p < pred_count; p++) + { + pred_node_id = incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]; + int32_t pred_idx_tmp = node_id_to_pos[pred_node_id] + 1; + // only predecessors that are less than score_matrix_height distant can be taken into account + if ((score_gIdx - pred_idx_tmp) < score_matrix_height) + { + int32_t trace_tmp = -(score_gIdx - pred_idx_tmp); + int32_t score_tmp = get_score_tb(scores, pred_idx_tmp, -1, score_matrix_height, band_width, band_shift, gradient, max_column, min_score_value); + if (penalty < score_tmp) + { + penalty = score_tmp; + traceback[index] = trace_tmp; + } + } + } + first_element_prev_score = penalty + gap_score; + set_score_tb(scores, score_gIdx, -1, score_matrix_height, first_element_prev_score, band_start, band_width); + } + } + } + pred_count = __shfl_sync(FULL_MASK, pred_count, 0); + pred_idx = __shfl_sync(FULL_MASK, pred_idx, 0); + //------------------------------------------------------------- + + SeqT graph_base = nodes[node_id]; + + for (int32_t read_pos = lane_idx * CUDAPOA_CELLS_PER_THREAD + band_start; read_pos < band_start + band_width; read_pos += CUDAPOA_MIN_BAND_WIDTH) + { + SeqT4* d_read4 = (SeqT4*)read; + SeqT4 read4 = d_read4[read_pos / CUDAPOA_CELLS_PER_THREAD]; + + TraceT4 trace; + ScoreT4 score = {min_score_value, min_score_value, min_score_value, min_score_value}; + // note that whenever accessing a score matrix row, the row needs to be mapped to [0, score_matrix_height) + get_scores_tb(scores, pred_idx, score_gIdx, read_pos, score_matrix_height, band_width, band_shift, gradient, + max_column, gap_score, match_score, mismatch_score, read4, graph_base, score, trace); + + // Perform same score updates as above, but for rest of predecessors. + for (int32_t p = 1; p < pred_count; p++) + { + int32_t pred_idx_tmp = node_id_to_pos[incoming_edges[node_id * CUDAPOA_MAX_NODE_EDGES + p]] + 1; + if ((score_gIdx - pred_idx_tmp) < score_matrix_height) + { + get_scores_tb(scores, pred_idx_tmp, score_gIdx, read_pos, score_matrix_height, band_width, band_shift, gradient, + max_column, gap_score, match_score, mismatch_score, read4, graph_base, score, trace); + } + } + + // While there are changes to the horizontal score values, keep updating the matrix. + // So loop will only run the number of time there are corrections in the matrix. + // The any_sync warp primitive lets us easily check if any of the threads had an update. + bool loop = true; + + while (__any_sync(FULL_MASK, loop)) + { + loop = false; + // Note: computation of s3 depends on s2, s2 depends on s1 and s1 on s0. + // If we reverse the order of computation in this loop from s3 to s0, it will increase + // ILP. However, in longer reads where indels are more frequent, this reverse computations + // results in larger number of iterations. Since if s0 is changed, value of s1, s2 and s3 which + // already have been computed in parallel need to be updated again. + + // The shfl_up lets us grab a value from the lane below. + int32_t last_score = __shfl_up_sync(FULL_MASK, score.s3, 1); + if (lane_idx == 0) + { + last_score = first_element_prev_score; + } + + if (score.s0 < last_score + gap_score) + { + score.s0 = last_score + gap_score; + trace.t0 = 0; + } + + if (score.s1 < score.s0 + gap_score) + { + score.s1 = score.s0 + gap_score; + trace.t1 = 0; + } + + if (score.s2 < score.s1 + gap_score) + { + score.s2 = score.s1 + gap_score; + trace.t2 = 0; + } + + int32_t tscore = max(score.s2 + gap_score, score.s3); + if (tscore > score.s3) + { + score.s3 = tscore; + trace.t3 = 0; + loop = true; + } + } + + // Copy over the last element score of the last lane into a register of first lane + // which can be used to compute the first cell of the next warp. + first_element_prev_score = __shfl_sync(FULL_MASK, score.s3, WARP_SIZE - 1); + + // row is mapped to [0, score_matrix_height) span + int64_t index = static_cast(read_pos + 1 - band_start) + static_cast(score_gIdx % score_matrix_height) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + scores[index] = score.s0; + scores[index + 1L] = score.s1; + scores[index + 2L] = score.s2; + scores[index + 3L] = score.s3; + + index = static_cast(read_pos + 1 - band_start) + static_cast(score_gIdx) * static_cast(band_width + CUDAPOA_BANDED_MATRIX_RIGHT_PADDING); + traceback[index] = trace.t0; + traceback[index + 1L] = trace.t1; + traceback[index + 2L] = trace.t2; + traceback[index + 3L] = trace.t3; + + __syncwarp(); + } + } + + int32_t aligned_nodes = 0; + if (lane_idx == 0) + { + // Find location of the maximum score in the matrix. + int32_t i = 0; + int32_t j = read_length; + int32_t mscore = min_score_value; + + for (int32_t idx = 1; idx <= graph_count; idx++) + { + if (outgoing_edge_count[graph[idx - 1]] == 0) + { + if ((graph_count - idx) < score_matrix_height) + { + int32_t s = get_score_tb(scores, idx, j, score_matrix_height, band_width, band_shift, gradient, max_column, min_score_value); + if (mscore < s) + { + mscore = s; + i = idx; + } + } + } + } + + // if i was not set, throw an error indicating selected score_matrix_height (i.e. max predecessor distance) is too small + if (i == 0) + { + j = 0; + aligned_nodes = CUDAPOA_KERNEL_NW_TRACEBACK_BUFFER_FAILED; + } + + //------------------------------------------------------------------------ + + // Fill in traceback + int32_t loop_count = 0; + while (!(i == 0 && j == 0) && loop_count < static_cast(read_length + graph_count + 2)) + { + loop_count++; + + int32_t band_start = get_band_start_for_row_tb(i, gradient, band_width, band_shift, max_column); + TraceT trace = get_trace(traceback, i, j, band_start, band_width); + + if (trace == 0) + { + // horizontal path (indel) + alignment_graph[aligned_nodes] = -1; + alignment_read[aligned_nodes] = j - 1; + j--; + } + else if (trace < 0) + { + // vertical path (indel) + alignment_graph[aligned_nodes] = graph[i - 1]; + alignment_read[aligned_nodes] = -1; + i += trace; + } + else + { + // diagonal path (match/mismatch) + alignment_graph[aligned_nodes] = graph[i - 1]; + alignment_read[aligned_nodes] = j - 1; + i -= trace; + j--; + + if (Adaptive) + { + // no need to request rerun if (a) it's not the first run, (b) band_width == CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH already + if (rerun == 0 && band_width < CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH) + { + // check if traceback gets too close or hits the band limits, if so stop and rerun with extended band-width + // threshold for proximity to band limits works better if defined proportionate to the sequence length + int32_t threshold = max(1, max_column / 1024); // ad-hoc rule 7 + if (j > threshold && j < max_column - threshold) + { + int32_t band_start = get_band_start_for_row(i, gradient, band_width, band_shift, max_column); + if (j <= band_start + threshold) // ad-hoc rule 8-a, too close to left bound + { + aligned_nodes = CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_LEFT; + break; + } + if (j >= (band_start + band_width - threshold)) // ad-hoc rule 8-b, too close to right bound + { + aligned_nodes = CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_RIGHT; + break; + } + } + } + } + } + + aligned_nodes++; + } + + if (loop_count >= (read_length + graph_count + 2)) + { + aligned_nodes = CUDAPOA_KERNEL_NW_BACKTRACKING_LOOP_FAILED; + } + +#ifdef NW_VERBOSE_PRINT + printf("aligned nodes %d, loop count %d\n", aligned_nodes, loop_count); +#endif + } + aligned_nodes = __shfl_sync(FULL_MASK, aligned_nodes, 0); + return aligned_nodes; +} + +// global kernel used in testing, hence uses int16_t for SizeT and ScoreT, +// may need to change if test inputs change to long reads +template +__global__ void runNeedlemanWunschBandedTBKernel(uint8_t* nodes, + SizeT* graph, + SizeT* node_id_to_pos, + int32_t graph_count, + uint16_t* incoming_edge_count, + SizeT* incoming_edges, + uint16_t* outgoing_edge_count, + uint8_t* read, + int32_t read_length, + int16_t* scores, + int16_t* traceback, + int32_t scores_width, + int32_t max_nodes_per_graph, + SizeT* alignment_graph, + SizeT* alignment_read, + int32_t band_width, + int32_t score_matrix_height, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, + SizeT* aligned_nodes, + bool adaptive) +{ + static_assert(std::is_same::value, "This function only accepts int16_t as SizeT."); + + float banded_buffer_size = static_cast(max_nodes_per_graph) * static_cast(scores_width); + + if (adaptive) + { + *aligned_nodes = needlemanWunschBandedTraceback(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + traceback, + banded_buffer_size, + alignment_graph, + alignment_read, + band_width, + score_matrix_height, + gap_score, + mismatch_score, + match_score, + 0); + } + else + { + *aligned_nodes = needlemanWunschBandedTraceback(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + traceback, + banded_buffer_size, + alignment_graph, + alignment_read, + band_width, + score_matrix_height, + gap_score, + mismatch_score, + match_score, + 0); + } +} + +// Host function that calls the kernel +template +void runNWbandedTB(uint8_t* nodes, + SizeT* graph, + SizeT* node_id_to_pos, + int32_t graph_count, + uint16_t* incoming_edge_count, + SizeT* incoming_edges, + uint16_t* outgoing_edge_count, + uint8_t* read, + int32_t read_length, + int16_t* scores, + int16_t* traceback, + int32_t scores_width, + int32_t max_nodes_per_graph, + SizeT* alignment_graph, + SizeT* alignment_read, + int32_t band_width, + int32_t score_matrix_height, + int32_t gap_score, + int32_t mismatch_score, + int32_t match_score, + SizeT* aligned_nodes, + bool adaptive) +{ + runNeedlemanWunschBandedTBKernel<<<1, CUDAPOA_BANDED_THREADS_PER_BLOCK>>>(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_length, + scores, + traceback, + scores_width, + max_nodes_per_graph, + alignment_graph, + alignment_read, + band_width, + score_matrix_height, + gap_score, + mismatch_score, + match_score, + aligned_nodes, + adaptive); + GW_CU_CHECK_ERR(cudaPeekAtLastError()); +} + +} // namespace cudapoa + +} // namespace genomeworks + +} // namespace claraparabricks diff --git a/cudapoa/src/cudapoa_structs.cuh b/cudapoa/src/cudapoa_structs.cuh index d2158a2f3..9a663de0d 100644 --- a/cudapoa/src/cudapoa_structs.cuh +++ b/cudapoa/src/cudapoa_structs.cuh @@ -26,14 +26,21 @@ // Maximum number of nodes aligned to each other. #define CUDAPOA_MAX_NODE_ALIGNMENTS 50 +// Size of read chunks for reading sequences +#define SIZE_OF_SeqT4 4 + // Dimensions for Banded alignment score matrix #define WARP_SIZE 32 -#define CELLS_PER_THREAD 4 -#define CUDAPOA_MIN_BAND_WIDTH (CELLS_PER_THREAD * WARP_SIZE) -#define CUDAPOA_BANDED_MATRIX_RIGHT_PADDING (CELLS_PER_THREAD * 2) +#define CUDAPOA_CELLS_PER_THREAD 4 +#define CUDAPOA_MIN_BAND_WIDTH (CUDAPOA_CELLS_PER_THREAD * WARP_SIZE) +#define CUDAPOA_BANDED_MATRIX_RIGHT_PADDING (CUDAPOA_CELLS_PER_THREAD * 2) // ad-hoc maximum band-width defined in adaptive banding #define CUDAPOA_MAX_ADAPTIVE_BAND_WIDTH 1536 +// rerun codes used in adaptive banding +#define CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_LEFT -10 +#define CUDAPOA_SHIFT_ADAPTIVE_BAND_TO_RIGHT -11 + #define CUDAPOA_THREADS_PER_BLOCK 64 #define CUDAPOA_BANDED_THREADS_PER_BLOCK WARP_SIZE #define CUDAPOA_MAX_CONSENSUS_PER_BLOCK 512 @@ -42,6 +49,11 @@ #define CUDAPOA_KERNEL_ERROR_ENCOUNTERED UINT8_MAX #define CUDAPOA_KERNEL_NOERROR_ENCOUNTERED 0 +// NW return error codes +#define CUDAPOA_KERNEL_NW_BACKTRACKING_LOOP_FAILED -1 +#define CUDAPOA_KERNEL_NW_ADAPTIVE_STORAGE_FAILED -2 +#define CUDAPOA_KERNEL_NW_TRACEBACK_BUFFER_FAILED -3 + namespace claraparabricks { @@ -99,11 +111,13 @@ struct InputDetails SizeT* sequence_begin_nodes_ids; }; -template +template struct AlignmentDetails { // Device buffer for the scoring matrix for all windows. ScoreT* scores; + // Device buffer for the backtracking matrix for all windows. + TraceT* traceback; /// Buffer for storing per row band start location in absolute score matrix for adaptive banding SizeT* band_starts; /// Buffer for storing per row band widths for adaptive banding @@ -116,7 +130,7 @@ struct AlignmentDetails // preallocated size of scores buffer size_t scorebuf_alloc_size = 0; - // Device buffers for alignment backtrace + // Device buffers for alignment traceback SizeT* alignment_graph; SizeT* alignment_read; }; @@ -187,6 +201,12 @@ struct SeqT4 SeqT r0, r1, r2, r3; }; +template <> +struct __align__(4) SeqT4 +{ + uint8_t r0, r1, r2, r3; +}; + template struct ScoreT4 { @@ -199,6 +219,24 @@ struct __align__(8) ScoreT4 int16_t s0, s1, s2, s3; }; +template +struct TraceT4 +{ + TraceT t0, t1, t2, t3; +}; + +template <> +struct __align__(8) TraceT4 +{ + int16_t t0, t1, t2, t3; +}; + +template <> +struct __align__(4) TraceT4 +{ + int8_t t0, t1, t2, t3; +}; + } // namespace cudapoa } // namespace genomeworks diff --git a/cudapoa/src/main.cpp b/cudapoa/src/main.cpp index 5897ba3b6..181ea5f1c 100644 --- a/cudapoa/src/main.cpp +++ b/cudapoa/src/main.cpp @@ -50,7 +50,7 @@ std::unique_ptr initialize_batch(int32_t mismatch_score, // Initialize CUDAPOA batch object for batched processing of POAs on the GPU. const int32_t device_id = 0; cudaStream_t stream = 0; - size_t mem_per_batch = gpu_mem_allocation * free; // Using 90% of GPU available memory for CUDAPOA batch. + int64_t mem_per_batch = gpu_mem_allocation * free; // Using 90% of GPU available memory for CUDAPOA batch. std::unique_ptr batch = create_batch(device_id, stream, @@ -67,6 +67,7 @@ std::unique_ptr initialize_batch(int32_t mismatch_score, void process_batch(Batch* batch, bool msa_flag, bool print, std::vector& list_of_group_ids, int id_offset) { batch->generate_poa(); + std::string error_message, error_hint; StatusType status = StatusType::success; if (msa_flag) @@ -78,14 +79,20 @@ void process_batch(Batch* batch, bool msa_flag, bool print, std::vector status = batch->get_msa(msa, output_status); if (status != StatusType::success) { - std::cerr << "Could not generate MSA for batch : " << status << std::endl; + decode_error(status, error_message, error_hint); + std::cerr << "Could not generate MSA for batch : " << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } for (int32_t g = 0; g < get_size(msa); g++) { if (output_status[g] != StatusType::success) { - std::cerr << "Error generating MSA for POA group " << list_of_group_ids[g + id_offset] << ". Error type " << output_status[g] << std::endl; + decode_error(output_status[g], error_message, error_hint); + std::cerr << "Error generating MSA for POA group " << list_of_group_ids[g + id_offset] << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } else { @@ -109,14 +116,20 @@ void process_batch(Batch* batch, bool msa_flag, bool print, std::vector status = batch->get_consensus(consensus, coverage, output_status); if (status != StatusType::success) { - std::cerr << "Could not generate consensus for batch : " << status << std::endl; + decode_error(status, error_message, error_hint); + std::cerr << "Could not generate consensus for batch : " << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } for (int32_t g = 0; g < get_size(consensus); g++) { if (output_status[g] != StatusType::success) { - std::cerr << "Error generating consensus for POA group " << list_of_group_ids[g + id_offset] << ". Error type " << output_status[g] << std::endl; + decode_error(output_status[g], error_message, error_hint); + std::cerr << "Error generating consensus for POA group " << list_of_group_ids[g + id_offset] << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; } else { @@ -158,6 +171,9 @@ int main(int argc, char* argv[]) } } + // for error code message + std::string error_message, error_hint; + // Create a vector of POA groups based on windows std::vector poa_groups(windows.size()); for (int32_t i = 0; i < get_size(windows); ++i) @@ -185,6 +201,8 @@ int main(int argc, char* argv[]) parameters.band_width, parameters.band_mode, parameters.adaptive_storage, + parameters.graph_length, + parameters.predecessor_disance, nullptr, parameters.gpu_mem_allocation, parameters.mismatch_score, @@ -294,7 +312,10 @@ int main(int argc, char* argv[]) if (status != StatusType::exceeded_maximum_poas && status != StatusType::success) { - std::cerr << "Could not add POA group " << batch_group_ids[i] << " to batch " << b << ". Error code " << status << std::endl; + decode_error(status, error_message, error_hint); + std::cerr << "Could not add POA group " << batch_group_ids[i] << " to batch " << b << std::endl; + std::cerr << error_message << std::endl + << error_hint << std::endl; i++; } } diff --git a/cudapoa/src/utils.cu b/cudapoa/src/utils.cu index 8f26ff9e5..ba37bf71e 100644 --- a/cudapoa/src/utils.cu +++ b/cudapoa/src/utils.cu @@ -34,6 +34,8 @@ void get_multi_batch_sizes(std::vector& list_of_batch_sizes, int32_t band_width /*= 256*/, BandMode band_mode /*= adaptive_band*/, float adaptive_storage_factor /*= 2.0f*/, + float graph_length_factor /*= 3.0f*/, + int32_t max_pred_distance /*= 0*/, std::vector* bins_capacity /*= nullptr*/, float gpu_memory_usage_quota /*= 0.9*/, int32_t mismatch_score /*= -6*/, @@ -52,9 +54,12 @@ void get_multi_batch_sizes(std::vector& list_of_batch_sizes, { max_read_length = std::max(max_read_length, entry.length); } - max_poas[i] = BatchBlock::estimate_max_poas(BatchConfig(max_read_length, get_size(poa_groups[i]), band_width, band_mode, adaptive_storage_factor), - msa_flag, gpu_memory_usage_quota, - mismatch_score, gap_score, match_score); + BatchConfig batch_size = BatchConfig(max_read_length, get_size(poa_groups[i]), band_width, band_mode, + adaptive_storage_factor, graph_length_factor, max_pred_distance); + + max_poas[i] = BatchBlock::estimate_max_poas(batch_size, msa_flag, gpu_memory_usage_quota, + mismatch_score, gap_score, match_score); + max_lengths[i] = max_read_length; } @@ -118,7 +123,7 @@ void get_multi_batch_sizes(std::vector& list_of_batch_sizes, { if (bins_frequency[j] > 0) { - list_of_batch_sizes.emplace_back(bins_max_length[j], bins_num_reads[j], band_width, band_mode, adaptive_storage_factor); + list_of_batch_sizes.emplace_back(bins_max_length[j], bins_num_reads[j], band_width, band_mode, adaptive_storage_factor, graph_length_factor, max_pred_distance); list_of_groups_per_batch.push_back(bins_group_list[j]); // check if poa_groups in the following bins can be merged into the current bin for (int32_t k = j + 1; k < num_bins; k++) diff --git a/cudapoa/tests/Test_CudapoaAddAlignment.cu b/cudapoa/tests/Test_CudapoaAddAlignment.cu index 84e4471ae..6a807cd62 100644 --- a/cudapoa/tests/Test_CudapoaAddAlignment.cu +++ b/cudapoa/tests/Test_CudapoaAddAlignment.cu @@ -36,9 +36,9 @@ namespace cudapoa class BasicAlignment { public: - BasicAlignment(std::vector nodes, SizeTVec2D outgoing_edges, - SizeTVec2D node_alignments, std::vector node_coverage_counts, - std::vector read, std::vector base_weights, std::vector alignment_graph, std::vector alignment_read) + BasicAlignment(std::vector nodes, Int16Vec2D outgoing_edges, + Int16Vec2D node_alignments, std::vector node_coverage_counts, + std::vector read, std::vector base_weights, std::vector alignment_graph, std::vector alignment_read) : graph(nodes, outgoing_edges, node_alignments, node_coverage_counts) , read_(read) , alignment_graph_(alignment_graph) @@ -47,7 +47,7 @@ public: //do nothing for now } - void get_alignments(SizeT* alignment_graph, SizeT* alignment_read, SizeT* alignment_length) const + void get_alignments(int16_t* alignment_graph, int16_t* alignment_read, int16_t* alignment_length) const { for (int i = 0; i < get_size(alignment_graph_); i++) { @@ -73,10 +73,10 @@ public: } } - void get_graph_buffers(SizeT* incoming_edges, uint16_t* incoming_edge_count, - SizeT* outgoing_edges, uint16_t* outgoing_edge_count, - uint8_t* nodes, SizeT* node_count, - SizeT* node_alignments, uint16_t* node_alignment_count, + void get_graph_buffers(int16_t* incoming_edges, uint16_t* incoming_edge_count, + int16_t* outgoing_edges, uint16_t* outgoing_edge_count, + uint8_t* nodes, int16_t* node_count, + int16_t* node_alignments, uint16_t* node_alignment_count, uint16_t* node_coverage_counts) const { if (!graph.is_complete()) @@ -89,7 +89,7 @@ public: graph.get_node_coverage_counts(node_coverage_counts); } - void get_alignment_buffers(SizeT* alignment_graph, SizeT* alignment_read, SizeT* alignment_length, + void get_alignment_buffers(int16_t* alignment_graph, int16_t* alignment_read, int16_t* alignment_length, uint8_t* read, int8_t* base_weights) const { get_alignments(alignment_graph, alignment_read, alignment_length); @@ -101,8 +101,8 @@ protected: BasicGraph graph; std::vector read_; std::vector base_weights_; - std::vector alignment_graph_; - std::vector alignment_read_; + std::vector alignment_graph_; + std::vector alignment_read_; }; typedef std::pair AddAlginmentTestPair; @@ -123,7 +123,7 @@ std::vector getAddAlignmentTestCases() * \ / * A */ - BasicGraph ans_1(SizeTVec2D({{}, {0}, {1}, {2, 4}, {1}})); + BasicGraph ans_1(Int16Vec2D({{}, {0}, {1}, {2, 4}, {1}})); BasicAlignment ali_1({'A', 'A', 'A', 'A'}, //nodes {{}, {0}, {1}, {2}}, //outgoing_edges {{}, {}, {}, {}}, //node_alignments @@ -143,7 +143,7 @@ std::vector getAddAlignmentTestCases() * final graph A — T — C — G — A * */ - BasicGraph ans_2(SizeTVec2D({{}, {0}, {1}, {2}, {3}})); + BasicGraph ans_2(Int16Vec2D({{}, {0}, {1}, {2}, {3}})); BasicAlignment ali_2({'A', 'T', 'C', 'G'}, //nodes {{}, {0}, {1}, {2}}, //outgoing_edges {{}, {}, {}, {}}, //node_alignments @@ -167,7 +167,7 @@ std::vector getAddAlignmentTestCases() * \ / * A */ - BasicGraph ans_3(SizeTVec2D({{}, {0}, {1, 4, 5}, {2}, {0}, {0}})); + BasicGraph ans_3(Int16Vec2D({{}, {0}, {1, 4, 5}, {2}, {0}, {0}})); BasicAlignment ali_3({'A', 'A', 'C', 'G', 'C'}, //nodes {{}, {0}, {1, 4}, {2}, {0}}, //outgoing_edges {{}, {}, {}, {}}, //node_alignments @@ -188,7 +188,7 @@ std::vector getAddAlignmentTestCases() * \_____________/ * */ - BasicGraph ans_4(SizeTVec2D({{}, {0}, {1}, {2}, {3, 0}})); + BasicGraph ans_4(Int16Vec2D({{}, {0}, {1}, {2}, {3, 0}})); BasicAlignment ali_4({'A', 'T', 'T', 'G', 'A'}, //nodes {{}, {0}, {1}, {2}, {3}}, //outgoing_edges {{}, {}, {}, {}}, //node_alignments @@ -213,7 +213,7 @@ std::vector getAddAlignmentTestCases() * T * */ - BasicGraph ans_5(SizeTVec2D({{}, {0}, {1}, {2, 6, 7}, {3}, {0}, {5}, {5}})); + BasicGraph ans_5(Int16Vec2D({{}, {0}, {1}, {2, 6, 7}, {3}, {0}, {5}, {5}})); BasicAlignment ali_5({'A', 'T', 'G', 'T', 'A', 'C', 'A'}, //nodes {{}, {0}, {1}, {2, 6}, {3}, {0}, {5}}, //outgoing_edges {{}, {}, {}, {}}, //node_alignments @@ -232,58 +232,57 @@ std::vector getAddAlignmentTestCases() // host function for calling the kernel to test topsort device function. BasicGraph testAddAlignment(const BasicAlignment& obj) { - typedef int16_t SizeT; //declare device buffer - uint8_t* nodes; - SizeT* node_count; - SizeT* node_alignments; - uint16_t* node_alignment_count; - SizeT* incoming_edges; - uint16_t* incoming_edge_count; - SizeT* outgoing_edges; - uint16_t* outgoing_edge_count; - uint16_t* incoming_edge_w; - uint16_t* outgoing_edge_w; - SizeT* alignment_length; - SizeT* graph; - SizeT* alignment_graph; - uint8_t* read; - int8_t* base_weights; - SizeT* alignment_read; - uint16_t* node_coverage_counts; - SizeT* sequence_begin_nodes_ids; - uint16_t* outgoing_edges_coverage; - uint16_t* outgoing_edges_coverage_count; - uint16_t s = 0; + uint8_t* nodes = nullptr; + int16_t* node_count = nullptr; + int16_t* node_alignments = nullptr; + uint16_t* node_alignment_count = nullptr; + int16_t* incoming_edges = nullptr; + uint16_t* incoming_edge_count = nullptr; + int16_t* outgoing_edges = nullptr; + uint16_t* outgoing_edge_count = nullptr; + uint16_t* incoming_edge_w = nullptr; + uint16_t* outgoing_edge_w = nullptr; + int16_t* alignment_length = nullptr; + int16_t* graph = nullptr; + int16_t* alignment_graph = nullptr; + uint8_t* read = nullptr; + int8_t* base_weights = nullptr; + int16_t* alignment_read = nullptr; + uint16_t* node_coverage_counts = nullptr; + int16_t* sequence_begin_nodes_ids = nullptr; + uint16_t* outgoing_edges_coverage = nullptr; + uint16_t* outgoing_edges_coverage_count = nullptr; + uint16_t s = 0; BatchConfig batch_size; // default max_sequence_size = 1024, max_sequences_per_poa = 100 //allocate unified memory so they can be accessed by both host and device. - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&nodes, batch_size.max_nodes_per_graph * sizeof(uint8_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_count, sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_alignments, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_ALIGNMENTS * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_alignment_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edge_w, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edge_w, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&alignment_length, sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&graph, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&alignment_graph, batch_size.max_sequence_size * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&read, batch_size.max_sequence_size * sizeof(uint8_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&base_weights, batch_size.max_sequence_size * sizeof(int8_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&alignment_read, batch_size.max_sequence_size * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_coverage_counts, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&sequence_begin_nodes_ids, batch_size.max_sequences_per_poa * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edges_coverage, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * batch_size.max_sequences_per_poa * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edges_coverage_count, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&nodes, batch_size.max_nodes_per_graph * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_count, sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_alignments, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_ALIGNMENTS * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_alignment_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edge_w, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edge_w, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&alignment_length, sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&graph, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&alignment_graph, batch_size.max_sequence_size * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&read, batch_size.max_sequence_size * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&base_weights, batch_size.max_sequence_size * sizeof(int8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&alignment_read, batch_size.max_sequence_size * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_coverage_counts, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&sequence_begin_nodes_ids, batch_size.max_sequences_per_poa * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edges_coverage, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * batch_size.max_sequences_per_poa * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edges_coverage_count, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); //initialize all 'count' buffers - memset((void**)node_alignment_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)incoming_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)outgoing_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)node_coverage_counts, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(node_alignment_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(incoming_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(outgoing_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(node_coverage_counts, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); //calculate edge counts on host //3 buffers are disregarded because they don't affect correctness -- incoming_edge_w, outgoing_edge_w, graph diff --git a/cudapoa/tests/Test_CudapoaGenerateConsensus.cu b/cudapoa/tests/Test_CudapoaGenerateConsensus.cu index d212c1258..bb884a308 100644 --- a/cudapoa/tests/Test_CudapoaGenerateConsensus.cu +++ b/cudapoa/tests/Test_CudapoaGenerateConsensus.cu @@ -35,20 +35,20 @@ class BasicGenerateConsensus { public: - BasicGenerateConsensus(std::vector nodes, std::vector sorted_graph, SizeTVec2D node_alignments, - SizeTVec2D outgoing_edges, std::vector node_coverage_counts, Uint16Vec2D outgoing_edge_w) + BasicGenerateConsensus(std::vector nodes, std::vector sorted_graph, Int16Vec2D node_alignments, + Int16Vec2D outgoing_edges, std::vector node_coverage_counts, Uint16Vec2D outgoing_edge_w) : graph_(nodes, sorted_graph, node_alignments, node_coverage_counts, outgoing_edges) , outgoing_edge_w_(outgoing_edge_w) , outgoing_edges_(outgoing_edges) { } - void get_graph_buffers(uint8_t* nodes, SizeT* node_count, - SizeT* sorted_poa, SizeT* node_id_to_pos, - SizeT* incoming_edges, uint16_t* incoming_edge_count, - SizeT* outgoing_edges, uint16_t* outgoing_edge_count, + void get_graph_buffers(uint8_t* nodes, int16_t* node_count, + int16_t* sorted_poa, int16_t* node_id_to_pos, + int16_t* incoming_edges, uint16_t* incoming_edge_count, + int16_t* outgoing_edges, uint16_t* outgoing_edge_count, uint16_t* incoming_edge_w, uint16_t* node_coverage_counts, - SizeT* node_alignments, uint16_t* node_alignment_count) const + int16_t* node_alignments, uint16_t* node_alignment_count) const { graph_.get_nodes(nodes, node_count); graph_.get_sorted_graph(sorted_poa); @@ -66,7 +66,7 @@ public: { for (int j = 0; j < get_size(outgoing_edges[i]); j++) { - SizeT to_node = outgoing_edges[i][j]; + int16_t to_node = outgoing_edges[i][j]; incoming_edge_w[to_node * CUDAPOA_MAX_NODE_EDGES + i] = outgoing_edge_w_[i][j]; } } @@ -74,7 +74,7 @@ public: protected: SortedGraph graph_; - SizeTVec2D outgoing_edges_; + Int16Vec2D outgoing_edges_; Uint16Vec2D outgoing_edge_w_; }; @@ -168,52 +168,52 @@ std::vector getGenerateConsensusTestCases() std::string testGenerateConsensus(const BasicGenerateConsensus& obj) { //declare device buffer - uint8_t* nodes; - SizeT* node_count; - SizeT* graph; - SizeT* node_id_to_pos; - SizeT* incoming_edges; - uint16_t* incoming_edge_count; - SizeT* outgoing_edges; - uint16_t* outgoing_edge_count; - uint16_t* incoming_edge_w; - uint16_t* node_coverage_counts; - SizeT* node_alignments; - uint16_t* node_alignment_count; + uint8_t* nodes = nullptr; + int16_t* node_count = nullptr; + int16_t* graph = nullptr; + int16_t* node_id_to_pos = nullptr; + int16_t* incoming_edges = nullptr; + uint16_t* incoming_edge_count = nullptr; + int16_t* outgoing_edges = nullptr; + uint16_t* outgoing_edge_count = nullptr; + uint16_t* incoming_edge_w = nullptr; + uint16_t* node_coverage_counts = nullptr; + int16_t* node_alignments = nullptr; + uint16_t* node_alignment_count = nullptr; //buffers that don't need initialization - SizeT* predecessors; - int32_t* scores; - uint8_t* consensus; - uint16_t* coverage; + int16_t* predecessors = nullptr; + int32_t* scores = nullptr; + uint8_t* consensus = nullptr; + uint16_t* coverage = nullptr; //default data size limits BatchConfig batch_size; //allocate unified memory so they can be accessed by both host and device. - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&nodes, batch_size.max_nodes_per_graph * sizeof(uint8_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_count, sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&graph, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_id_to_pos, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edge_w, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_coverage_counts, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_alignments, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_ALIGNMENTS * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_alignment_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&predecessors, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&scores, batch_size.max_nodes_per_graph * sizeof(int32_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&consensus, batch_size.max_consensus_size * sizeof(uint8_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&coverage, batch_size.max_consensus_size * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&nodes, batch_size.max_nodes_per_graph * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_count, sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&graph, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_id_to_pos, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edge_w, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_coverage_counts, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_alignments, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_ALIGNMENTS * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_alignment_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + + GW_CU_CHECK_ERR(cudaMallocManaged(&predecessors, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&scores, batch_size.max_nodes_per_graph * sizeof(int32_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&consensus, batch_size.max_consensus_size * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&coverage, batch_size.max_consensus_size * sizeof(uint16_t))); //initialize all 'count' buffers - memset((void**)incoming_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)outgoing_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)node_coverage_counts, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)node_alignment_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(incoming_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(outgoing_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(node_coverage_counts, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(node_alignment_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); //calculate edge counts on host obj.get_graph_buffers(nodes, node_count, @@ -224,23 +224,23 @@ std::string testGenerateConsensus(const BasicGenerateConsensus& obj) node_alignments, node_alignment_count); // call the host wrapper of topsort kernel - generateConsensusTestHost(nodes, - *node_count, - graph, - node_id_to_pos, - incoming_edges, - incoming_edge_count, - outgoing_edges, - outgoing_edge_count, - incoming_edge_w, - predecessors, - scores, - consensus, - coverage, - node_coverage_counts, - node_alignments, - node_alignment_count, - batch_size.max_consensus_size); + generateConsensusTestHost(nodes, + *node_count, + graph, + node_id_to_pos, + incoming_edges, + incoming_edge_count, + outgoing_edges, + outgoing_edge_count, + incoming_edge_w, + predecessors, + scores, + consensus, + coverage, + node_coverage_counts, + node_alignments, + node_alignment_count, + batch_size.max_consensus_size); GW_CU_CHECK_ERR(cudaDeviceSynchronize()); diff --git a/cudapoa/tests/Test_CudapoaGenerateMSA2.cu b/cudapoa/tests/Test_CudapoaGenerateMSA2.cu index 07d767c1c..2567c4c06 100644 --- a/cudapoa/tests/Test_CudapoaGenerateMSA2.cu +++ b/cudapoa/tests/Test_CudapoaGenerateMSA2.cu @@ -117,9 +117,8 @@ TEST_F(MSATest, CudapoaMSA) auto spoa_msa = spoa_generate_multiple_sequence_alignments(sequences); #ifndef SPOA_ACCURATE - for (int32_t i = 0; i < spoa_msa.size(); i++) + for (size_t i = 0; i < spoa_msa.size(); i++) { - std::string msa = cudapoa_msa[0][i]; msa.erase(std::remove(msa.begin(), msa.end(), '-'), msa.end()); ASSERT_EQ(msa, sequences[i]); diff --git a/cudapoa/tests/Test_CudapoaNW.cu b/cudapoa/tests/Test_CudapoaNW.cu index 87856507e..2d5a56481 100644 --- a/cudapoa/tests/Test_CudapoaNW.cu +++ b/cudapoa/tests/Test_CudapoaNW.cu @@ -20,6 +20,7 @@ #include //GW_CU_CHECK_ERR #include //array_to_string #include //get_size +#include #include "gtest/gtest.h" @@ -41,7 +42,7 @@ public: const static int16_t match_score_ = 8; public: - BasicNW(std::vector nodes, std::vector sorted_graph, SizeTVec2D outgoing_edges, + BasicNW(std::vector nodes, std::vector sorted_graph, Int16Vec2D outgoing_edges, std::vector read) : graph_(nodes, sorted_graph, outgoing_edges) , read_(read) @@ -51,10 +52,10 @@ public: BasicNW() = delete; - void get_graph_buffers(SizeT* incoming_edges, uint16_t* incoming_edge_count, - SizeT* outgoing_edges, uint16_t* outgoing_edge_count, - uint8_t* nodes, SizeT* node_count, - SizeT* graph, SizeT* node_id_to_pos) const + void get_graph_buffers(int16_t* incoming_edges, uint16_t* incoming_edge_count, + int16_t* outgoing_edges, uint16_t* outgoing_edge_count, + uint8_t* nodes, int16_t* node_count, + int16_t* graph, int16_t* node_id_to_pos) const { graph_.get_edges(incoming_edges, incoming_edge_count, outgoing_edges, outgoing_edge_count); graph_.get_nodes(nodes, node_count); @@ -185,50 +186,45 @@ std::vector getNWTestCases() return test_cases; } -// host function for calling the kernel to test topsort device function. +// host function for calling the kernel to test full-band NW device function. NWAnswer testNW(const BasicNW& obj) { - typedef int16_t SizeT; - //declare device buffer - uint8_t* nodes; - SizeT* graph; - SizeT* node_id_to_pos; - SizeT graph_count; //local - uint16_t* incoming_edge_count; - SizeT* incoming_edges; - uint16_t* outgoing_edge_count; - SizeT* outgoing_edges; - uint8_t* read; - uint16_t read_count; //local - int16_t* scores; - SizeT* alignment_graph; - SizeT* alignment_read; - int16_t gap_score; - int16_t mismatch_score; - int16_t match_score; - SizeT* aligned_nodes; //local; to store num of nodes aligned (length of alignment_graph and alignment_read) - BatchConfig batch_size; //default max_sequence_size = 1024, max_sequences_per_poa = 100 + uint8_t* nodes = nullptr; + int16_t* graph = nullptr; + int16_t* node_id_to_pos = nullptr; + int16_t graph_count = 0; //local + uint16_t* incoming_edge_count = nullptr; + int16_t* incoming_edges = nullptr; + uint16_t* outgoing_edge_count = nullptr; + int16_t* outgoing_edges = nullptr; + uint8_t* read = nullptr; + uint16_t read_count = 0; //local + int16_t* scores = nullptr; + int16_t* alignment_graph = nullptr; + int16_t* alignment_read = nullptr; + int16_t* aligned_nodes = nullptr; //local; to store num of nodes aligned (length of alignment_graph and alignment_read) + BatchConfig batch_size; //default max_sequence_size = 1024, max_sequences_per_poa = 100 //allocate unified memory so they can be accessed by both host and device. - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&nodes, batch_size.max_nodes_per_graph * sizeof(uint8_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&graph, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&node_id_to_pos, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&scores, batch_size.matrix_graph_dimension * batch_size.matrix_sequence_dimension * sizeof(int16_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&alignment_graph, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&read, batch_size.max_sequence_size * sizeof(uint8_t))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&alignment_read, batch_size.max_nodes_per_graph * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&aligned_nodes, sizeof(SizeT))); + GW_CU_CHECK_ERR(cudaMallocManaged(&nodes, batch_size.max_nodes_per_graph * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&graph, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_id_to_pos, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&scores, batch_size.max_nodes_per_graph * batch_size.matrix_sequence_dimension * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&alignment_graph, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&read, batch_size.max_sequence_size * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&alignment_read, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&aligned_nodes, sizeof(int16_t))); //initialize all 'count' buffers - memset((void**)incoming_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)outgoing_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); - memset((void**)node_id_to_pos, 0, batch_size.max_nodes_per_graph * sizeof(SizeT)); - memset((void**)scores, 0, batch_size.matrix_graph_dimension * batch_size.matrix_sequence_dimension * sizeof(int16_t)); + memset(incoming_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(outgoing_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(node_id_to_pos, 0, batch_size.max_nodes_per_graph * sizeof(int16_t)); + memset(scores, 0, batch_size.max_nodes_per_graph * batch_size.matrix_sequence_dimension * sizeof(int16_t)); //calculate edge counts on host obj.get_graph_buffers(incoming_edges, incoming_edge_count, @@ -236,35 +232,35 @@ NWAnswer testNW(const BasicNW& obj) nodes, &graph_count, graph, node_id_to_pos); obj.get_read_buffers(read, &read_count); - gap_score = BasicNW::gap_score_; - mismatch_score = BasicNW::mismatch_score_; - match_score = BasicNW::match_score_; + int32_t gap_score = BasicNW::gap_score_; + int32_t mismatch_score = BasicNW::mismatch_score_; + int32_t match_score = BasicNW::match_score_; //call the host wrapper of nw kernel - runNW(nodes, - graph, - node_id_to_pos, - graph_count, - incoming_edge_count, - incoming_edges, - outgoing_edge_count, - read, - read_count, - scores, - BatchConfig().matrix_sequence_dimension, - alignment_graph, - alignment_read, - gap_score, - mismatch_score, - match_score, - aligned_nodes); + runNW(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_count, + scores, + batch_size.matrix_sequence_dimension, + alignment_graph, + alignment_read, + gap_score, + mismatch_score, + match_score, + aligned_nodes); GW_CU_CHECK_ERR(cudaDeviceSynchronize()); //input and output buffers are the same ones in unified memory, so the results are updated in place //results are stored in alignment_graph and alignment_read; return string representation of those - auto res = std::make_pair(genomeworks::stringutils::array_to_string(alignment_graph, *aligned_nodes, ","), - genomeworks::stringutils::array_to_string(alignment_read, *aligned_nodes, ",")); + auto res = std::make_pair(genomeworks::stringutils::array_to_string(alignment_graph, *aligned_nodes, ","), + genomeworks::stringutils::array_to_string(alignment_read, *aligned_nodes, ",")); GW_CU_CHECK_ERR(cudaFree(nodes)); GW_CU_CHECK_ERR(cudaFree(graph)); @@ -304,6 +300,213 @@ TEST_P(NWTest, TestNWCorrectness) INSTANTIATE_TEST_SUITE_P(TestNW, NWTest, ValuesIn(getNWTestCases())); +//--------------------------------------------------------------------------------------- + +// host function for calling the kernels to test static/adaptive-band NW with/without traceback buffer +NWAnswer testNWbanded(const BasicNW& obj, bool adaptive, bool traceback = false) +{ + //declare device buffer + uint8_t* nodes = nullptr; + int16_t* graph = nullptr; + int16_t* node_id_to_pos = nullptr; + int16_t graph_count = 0; //local + uint16_t* incoming_edge_count = nullptr; + int16_t* incoming_edges = nullptr; + uint16_t* outgoing_edge_count = nullptr; + int16_t* outgoing_edges = nullptr; + uint8_t* read = nullptr; + uint16_t read_count = 0; //local + int16_t* scores = nullptr; + int16_t* traces = nullptr; + int16_t* alignment_graph = nullptr; + int16_t* alignment_read = nullptr; + int16_t* aligned_nodes = nullptr; //local; to store num of nodes aligned (length of alignment_graph and alignment_read) + BandMode band_mode = traceback ? (adaptive ? BandMode::adaptive_band_traceback : BandMode::static_band_traceback) + : (adaptive ? BandMode::adaptive_band : BandMode::static_band); + BatchConfig batch_size(1024 /*max_sequence_size*/, 2 /*max_sequences_per_poa*/, + 128 /*= band_width*/, band_mode); + + //allocate unified memory so they can be accessed by both host and device. + GW_CU_CHECK_ERR(cudaMallocManaged(&nodes, batch_size.max_nodes_per_graph * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&graph, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&node_id_to_pos, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edges, batch_size.max_nodes_per_graph * CUDAPOA_MAX_NODE_EDGES * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edge_count, batch_size.max_nodes_per_graph * sizeof(uint16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&alignment_graph, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&read, batch_size.max_sequence_size * sizeof(uint8_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&alignment_read, batch_size.max_nodes_per_graph * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&aligned_nodes, sizeof(int16_t))); + if (traceback) + { + GW_CU_CHECK_ERR(cudaMallocManaged(&scores, batch_size.max_banded_pred_distance * batch_size.matrix_sequence_dimension * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&traces, batch_size.max_nodes_per_graph * batch_size.matrix_sequence_dimension * sizeof(int16_t))); + } + else + { + GW_CU_CHECK_ERR(cudaMallocManaged(&scores, batch_size.max_nodes_per_graph * batch_size.matrix_sequence_dimension * sizeof(int16_t))); + } + + //initialize all 'count' buffers + memset(incoming_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(outgoing_edge_count, 0, batch_size.max_nodes_per_graph * sizeof(uint16_t)); + memset(node_id_to_pos, 0, batch_size.max_nodes_per_graph * sizeof(int16_t)); + memset(scores, 0, batch_size.max_nodes_per_graph * batch_size.matrix_sequence_dimension * sizeof(int16_t)); + + //calculate edge counts on host + obj.get_graph_buffers(incoming_edges, incoming_edge_count, + outgoing_edges, outgoing_edge_count, + nodes, &graph_count, + graph, node_id_to_pos); + obj.get_read_buffers(read, &read_count); + int32_t gap_score = BasicNW::gap_score_; + int32_t mismatch_score = BasicNW::mismatch_score_; + int32_t match_score = BasicNW::match_score_; + + //call the host wrapper of nw kernels + if (traceback) + { + runNWbandedTB(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_count, + scores, + traces, + batch_size.matrix_sequence_dimension, + batch_size.max_nodes_per_graph, + alignment_graph, + alignment_read, + batch_size.alignment_band_width, + batch_size.max_banded_pred_distance, + gap_score, + mismatch_score, + match_score, + aligned_nodes, + adaptive); + } + else + { + runNWbanded(nodes, + graph, + node_id_to_pos, + graph_count, + incoming_edge_count, + incoming_edges, + outgoing_edge_count, + read, + read_count, + scores, + batch_size.matrix_sequence_dimension, + batch_size.max_nodes_per_graph, + alignment_graph, + alignment_read, + batch_size.alignment_band_width, + gap_score, + mismatch_score, + match_score, + aligned_nodes, + adaptive); + } + + GW_CU_CHECK_ERR(cudaDeviceSynchronize()); + + //input and output buffers are the same ones in unified memory, so the results are updated in place + //results are stored in alignment_graph and alignment_read; return string representation of those + auto res = std::make_pair(genomeworks::stringutils::array_to_string(alignment_graph, *aligned_nodes, ","), + genomeworks::stringutils::array_to_string(alignment_read, *aligned_nodes, ",")); + + GW_CU_CHECK_ERR(cudaFree(nodes)); + GW_CU_CHECK_ERR(cudaFree(graph)); + GW_CU_CHECK_ERR(cudaFree(node_id_to_pos)); + GW_CU_CHECK_ERR(cudaFree(incoming_edges)); + GW_CU_CHECK_ERR(cudaFree(incoming_edge_count)); + GW_CU_CHECK_ERR(cudaFree(outgoing_edges)); + GW_CU_CHECK_ERR(cudaFree(outgoing_edge_count)); + GW_CU_CHECK_ERR(cudaFree(scores)); + GW_CU_CHECK_ERR(cudaFree(alignment_graph)); + GW_CU_CHECK_ERR(cudaFree(read)); + GW_CU_CHECK_ERR(cudaFree(alignment_read)); + GW_CU_CHECK_ERR(cudaFree(aligned_nodes)); + if (traceback) + { + GW_CU_CHECK_ERR(cudaFree(traces)); + } + + return res; +} + +class NWbandedTest : public ::testing::Test +{ +public: + std::unique_ptr nw; + +public: + void SetUp() + { + // initialize nw graph and read with the following data + std::string nodes_str = "TTTAACCTAATAAATCAGTGAAGATTTAAAATATGATAATTATTGATTTTGGTGAGAGTGCAAAGAAATTTGTTACCCTCATAAGCTGAGCAGACAGATAAGATAGAAAAACAGAAGATAGAATATTAAAACCATGATAGGTACAGACTGAAAAATTCTTGGATAAATATTAAAATTTAGGCTTTAGTAGTAGATTGATGACTGTGAGGAAAAAGGATGTCCAATTGTTGAGTGACATGTAGAATGCCTTAAAATAATTTTACACGTCACTGAAAGCTATATTTATATTCAGGAAGGATATATCCCAGTCATGATTTTCTTAATAAGTTGCCCCATTTTCCAAGTTTAGCTAATTAACATTTATGTCTTCTATAATCAGGAATAGTCATTAACTGACACAGAAACAATTGGAAGCATATGTAGCCAAAAACATAAAAATTATTGCATCCAAATAATGATAAAGTAAAATATTAAAAAATATAGTCTTCTAAAT"; + std::string read_str = "TTTCACCTAGAAAATCAGTGAAGATTTAACAAAAAAAAAAAAAAAAAAAAAAAAATATTGATAATTATTGATTTTGGTGAGAGTGCAAAGCAATTGGCTACCCTCATAAGCTGAGCAGAAGATAAGATAGACAACAGAAGATAGAATAGTTAAACCATGATAGGTACAGACTGCAAAAAAATTCGATAAATATTAAAATTTAGGGCTTTAGTATATATTGATGACTGAGAAAAATCGTGATGTGCAATTGTGCGTGACATGTAGAATTGCCTTAAATAAAATTTAATCTGTCACTGAAGCTATATTTATATTCAGGAAGGATATATCCCAGTCATTGCTTTTCTTAATAAGTGCCCATGTTCCAAGTTTAGCCTAATTAAAAACTTTATGTCTTCTATATCAGAATAGTCATTAATGCACAGAAACAATTTGCGAAGGCATTATGTAGCAAAAACATAAAAAATTATTGCAGCCAAATAATGAATAAAAGTAACACAATCATTTAAAAAAATTATTATGTACTTCTAAAC"; + // extract data to build BasicNW + std::vector nodes(nodes_str.begin(), nodes_str.end()); + std::vector sorted_graph(nodes.size()); + std::iota(sorted_graph.begin(), sorted_graph.end(), 0); + Int16Vec2D outgoing_edges(nodes.size()); + for (size_t i = 0; i < outgoing_edges.size() - 1; i++) + { + outgoing_edges[i].push_back(i + 1); + } + std::vector read(read_str.begin(), read_str.end()); + // setup nw + nw = std::make_unique(nodes, sorted_graph, outgoing_edges, read); + } +}; + +TEST_F(NWbandedTest, NWStaticBandvsFull) +{ + auto full_alignment_results = testNW(*nw); + auto static_banded_results = testNWbanded(*nw, false); + // verify alignment_graph + EXPECT_EQ(full_alignment_results.first, static_banded_results.first); + // verify alignment_read + EXPECT_EQ(full_alignment_results.second, static_banded_results.second); +} + +TEST_F(NWbandedTest, NWAdaptiveBandvsFull) +{ + auto full_alignment_results = testNW(*nw); + auto adaptive_banded_results = testNWbanded(*nw, true); + // verify alignment_graph + EXPECT_EQ(full_alignment_results.first, adaptive_banded_results.first); + // verify alignment_read + EXPECT_EQ(full_alignment_results.second, adaptive_banded_results.second); +} + +TEST_F(NWbandedTest, NWStaticBandTracebackvsFull) +{ + auto full_alignment_results = testNW(*nw); + auto static_banded_tb_results = testNWbanded(*nw, false, true); + // verify alignment_graph + EXPECT_EQ(full_alignment_results.first, static_banded_tb_results.first); + // verify alignment_read + EXPECT_EQ(full_alignment_results.second, static_banded_tb_results.second); +} + +TEST_F(NWbandedTest, NWAdaptiveBandTracebackvsFull) +{ + auto full_alignment_results = testNW(*nw); + auto adaptive_banded_tb_results = testNWbanded(*nw, true, true); + // verify alignment_graph + EXPECT_EQ(full_alignment_results.first, adaptive_banded_tb_results.first); + // verify alignment_read + EXPECT_EQ(full_alignment_results.second, adaptive_banded_tb_results.second); +} + } // namespace cudapoa } // namespace genomeworks diff --git a/cudapoa/tests/Test_CudapoaSerializeGraph.cpp b/cudapoa/tests/Test_CudapoaSerializeGraph.cpp index 5db2dba69..7866df5bb 100644 --- a/cudapoa/tests/Test_CudapoaSerializeGraph.cpp +++ b/cudapoa/tests/Test_CudapoaSerializeGraph.cpp @@ -48,7 +48,7 @@ class GraphTest : public ::testing::Test size_t total = 0, free = 0; cudaSetDevice(device_id); cudaMemGetInfo(&free, &total); - size_t mem_per_batch = 0.9 * free; + int64_t mem_per_batch = 0.9 * free; BatchConfig batch_size(1024, max_sequences_per_poa); cudapoa_batch = genomeworks::cudapoa::create_batch(device_id, stream, mem_per_batch, output_mask, batch_size, gap_score, mismatch_score, match_score); diff --git a/cudapoa/tests/Test_CudapoaTopSort.cu b/cudapoa/tests/Test_CudapoaTopSort.cu index 2e11de733..6867a3789 100644 --- a/cudapoa/tests/Test_CudapoaTopSort.cu +++ b/cudapoa/tests/Test_CudapoaTopSort.cu @@ -34,7 +34,7 @@ namespace cudapoa { // alias for a test case (answer, graph) -typedef std::pair TopSortTestPair; +typedef std::pair TopSortTestPair; using ::testing::TestWithParam; using ::testing::ValuesIn; @@ -45,15 +45,15 @@ std::vector getTopSortTestCases() std::vector test_cases; - SizeTVec2D outgoing_edges_1 = {{}, {}, {3}, {1}, {0, 1}, {0, 2}}; + Int16Vec2D outgoing_edges_1 = {{}, {}, {3}, {1}, {0, 1}, {0, 2}}; std::string answer_1 = "4-5-0-2-3-1"; test_cases.emplace_back(answer_1, outgoing_edges_1); - SizeTVec2D outgoing_edges_2 = {{1, 3}, {2, 3}, {3, 4, 5}, {4, 5}, {5}, {}}; + Int16Vec2D outgoing_edges_2 = {{1, 3}, {2, 3}, {3, 4, 5}, {4, 5}, {5}, {}}; std::string answer_2 = "0-1-2-3-4-5"; test_cases.emplace_back(answer_2, outgoing_edges_2); - SizeTVec2D outgoing_edges_3 = {{}, {}, {3}, {1}, {0, 1, 7}, {0, 2}, {4}, {5}}; + Int16Vec2D outgoing_edges_3 = {{}, {}, {3}, {1}, {0, 1, 7}, {0, 2}, {4}, {5}}; std::string answer_3 = "6-4-7-5-0-2-3-1"; test_cases.emplace_back(answer_3, outgoing_edges_3); @@ -63,33 +63,33 @@ std::vector getTopSortTestCases() } // host function for calling the kernel to test topsort device function. -std::string testTopSortDeviceUtil(SizeT node_count, SizeTVec2D outgoing_edges_vec) +std::string testTopSortDeviceUtil(int16_t node_count, Int16Vec2D outgoing_edges_vec) { //declare device buffer - SizeT* sorted_poa; - SizeT* sorted_poa_node_map; - uint16_t* incoming_edge_count; - SizeT* outgoing_edges; - uint16_t* outgoing_edge_count; - uint16_t* local_incoming_edge_count; + int16_t* sorted_poa = nullptr; + int16_t* sorted_poa_node_map = nullptr; + uint16_t* incoming_edge_count = nullptr; + int16_t* outgoing_edges = nullptr; + uint16_t* outgoing_edge_count = nullptr; + uint16_t* local_incoming_edge_count = nullptr; size_t graph_size = node_count * sizeof(uint16_t); //allocate unified memory so they can be accessed by both host and device. - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&sorted_poa, node_count * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&sorted_poa_node_map, node_count * sizeof(SizeT))); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&incoming_edge_count, graph_size)); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edges, node_count * sizeof(SizeT) * CUDAPOA_MAX_NODE_EDGES)); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&outgoing_edge_count, graph_size)); - GW_CU_CHECK_ERR(cudaMallocManaged((void**)&local_incoming_edge_count, graph_size)); + GW_CU_CHECK_ERR(cudaMallocManaged(&sorted_poa, node_count * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&sorted_poa_node_map, node_count * sizeof(int16_t))); + GW_CU_CHECK_ERR(cudaMallocManaged(&incoming_edge_count, graph_size)); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edges, node_count * sizeof(int16_t) * CUDAPOA_MAX_NODE_EDGES)); + GW_CU_CHECK_ERR(cudaMallocManaged(&outgoing_edge_count, graph_size)); + GW_CU_CHECK_ERR(cudaMallocManaged(&local_incoming_edge_count, graph_size)); //initialize incoming_edge_count & local_incoming_edge_count - memset((void**)incoming_edge_count, 0, graph_size); - memset((void**)local_incoming_edge_count, 0, graph_size); + memset(incoming_edge_count, 0, graph_size); + memset(local_incoming_edge_count, 0, graph_size); //calculate edge counts on host - SizeT out_node; + int16_t out_node; for (int i = 0; i < node_count; i++) { outgoing_edge_count[i] = get_size(outgoing_edges_vec[i]); @@ -103,17 +103,17 @@ std::string testTopSortDeviceUtil(SizeT node_count, SizeTVec2D outgoing_edges_ve } // call the host wrapper of topsort kernel - runTopSort(sorted_poa, - sorted_poa_node_map, - node_count, - incoming_edge_count, - outgoing_edges, - outgoing_edge_count, - local_incoming_edge_count); + runTopSort(sorted_poa, + sorted_poa_node_map, + node_count, + incoming_edge_count, + outgoing_edges, + outgoing_edge_count, + local_incoming_edge_count); GW_CU_CHECK_ERR(cudaDeviceSynchronize()); - std::string res = genomeworks::stringutils::array_to_string(sorted_poa, node_count); + std::string res = genomeworks::stringutils::array_to_string(sorted_poa, node_count); GW_CU_CHECK_ERR(cudaFree(sorted_poa)); GW_CU_CHECK_ERR(cudaFree(sorted_poa_node_map)); @@ -130,7 +130,7 @@ class TopSortDeviceUtilTest : public TestWithParam public: void SetUp() {} - std::string runTopSortDevice(SizeTVec2D outgoing_edges) + std::string runTopSortDevice(Int16Vec2D outgoing_edges) { return testTopSortDeviceUtil(get_size(outgoing_edges), outgoing_edges); } diff --git a/cudapoa/tests/basic_graph.hpp b/cudapoa/tests/basic_graph.hpp index 08bcd4b52..35527a420 100644 --- a/cudapoa/tests/basic_graph.hpp +++ b/cudapoa/tests/basic_graph.hpp @@ -31,17 +31,15 @@ namespace genomeworks namespace cudapoa { -// in all tests, SizeT can be considered int16_t -typedef int16_t SizeT; // alias for the 2d vector graph representation -typedef std::vector> SizeTVec2D; +typedef std::vector> Int16Vec2D; typedef std::vector>> Uint16Vec3D; typedef std::vector> Uint16Vec2D; class BasicGraph { public: - BasicGraph(std::vector nodes, SizeTVec2D outgoing_edges, SizeTVec2D node_alignments, std::vector node_coverage_counts, Uint16Vec3D outgoing_edges_coverage = {}) + BasicGraph(std::vector nodes, Int16Vec2D outgoing_edges, Int16Vec2D node_alignments, std::vector node_coverage_counts, Uint16Vec3D outgoing_edges_coverage = {}) : nodes_(nodes) , outgoing_edges_(outgoing_edges) , node_alignments_(node_alignments) @@ -52,20 +50,20 @@ class BasicGraph node_count_ = get_size(nodes_); } - BasicGraph(SizeT* outgoing_edges, uint16_t* outgoing_edge_count, SizeT node_count) + BasicGraph(int16_t* outgoing_edges, uint16_t* outgoing_edge_count, int16_t node_count) { graph_complete_ = false; outgoing_edges_ = edges_to_graph(outgoing_edges, outgoing_edge_count, node_count); } - BasicGraph(SizeTVec2D outgoing_edges) + BasicGraph(Int16Vec2D outgoing_edges) { graph_complete_ = false; outgoing_edges_ = outgoing_edges; node_count_ = get_size(outgoing_edges); } - BasicGraph(std::vector nodes, SizeTVec2D outgoing_edges) + BasicGraph(std::vector nodes, Int16Vec2D outgoing_edges) : BasicGraph(outgoing_edges) { nodes_ = nodes; @@ -74,10 +72,10 @@ class BasicGraph BasicGraph() = delete; //fill in the edge-related pointers based on stored graph - void get_edges(SizeT* incoming_edges, uint16_t* incoming_edge_count, - SizeT* outgoing_edges, uint16_t* outgoing_edge_count) const + void get_edges(int16_t* incoming_edges, uint16_t* incoming_edge_count, + int16_t* outgoing_edges, uint16_t* outgoing_edge_count) const { - SizeT out_node; + int16_t out_node; for (int i = 0; i < node_count_; i++) { outgoing_edge_count[i] = get_size(outgoing_edges_[i]); @@ -92,7 +90,7 @@ class BasicGraph } } //fill in the nodes and node_count pointer - void get_nodes(uint8_t* nodes, SizeT* node_count) const + void get_nodes(uint8_t* nodes, int16_t* node_count) const { for (int i = 0; i < get_size(nodes_); i++) { @@ -101,9 +99,9 @@ class BasicGraph *node_count = node_count_; } //fill in the node_alignments and node_alignment_count pointers - void get_node_alignments(SizeT* node_alignments, uint16_t* node_alignment_count) const + void get_node_alignments(int16_t* node_alignments, uint16_t* node_alignment_count) const { - SizeT aligned_node; + int16_t aligned_node; for (int i = 0; i < get_size(node_alignments_); i++) { for (int j = 0; j < get_size(node_alignments_[i]); j++) @@ -124,9 +122,9 @@ class BasicGraph } // convert results from outgoing_edges to Uint16Vec2D graph - SizeTVec2D edges_to_graph(SizeT* outgoing_edges, uint16_t* outgoing_edge_count, uint16_t node_count) + Int16Vec2D edges_to_graph(int16_t* outgoing_edges, uint16_t* outgoing_edge_count, uint16_t node_count) { - SizeTVec2D graph(node_count); + Int16Vec2D graph(node_count); for (uint16_t i = 0; i < node_count; i++) { for (uint16_t j = 0; j < outgoing_edge_count[i]; j++) @@ -165,14 +163,14 @@ class BasicGraph return this->outgoing_edges_ == rhs.outgoing_edges_; } - const SizeTVec2D& get_outgoing_edges() const { return outgoing_edges_; } + const Int16Vec2D& get_outgoing_edges() const { return outgoing_edges_; } protected: bool graph_complete_; std::vector nodes_; - SizeTVec2D outgoing_edges_; //this uniquely represents the graph structure; equality of BasicGraph is based on this member. + Int16Vec2D outgoing_edges_; //this uniquely represents the graph structure; equality of BasicGraph is based on this member. Uint16Vec3D outgoing_edges_coverage_; - SizeTVec2D node_alignments_; + Int16Vec2D node_alignments_; std::vector node_coverage_counts_; uint16_t node_count_; }; diff --git a/cudapoa/tests/sorted_graph.hpp b/cudapoa/tests/sorted_graph.hpp index b398667ee..2dbfd190d 100644 --- a/cudapoa/tests/sorted_graph.hpp +++ b/cudapoa/tests/sorted_graph.hpp @@ -36,16 +36,16 @@ class SortedGraph : public BasicGraph { public: - SortedGraph(std::vector nodes, std::vector sorted_graph, SizeTVec2D outgoing_edges) + SortedGraph(std::vector nodes, std::vector sorted_graph, Int16Vec2D outgoing_edges) : BasicGraph(nodes, outgoing_edges) , sorted_graph_(sorted_graph) { // do nothing for now } - SortedGraph(std::vector nodes, std::vector sorted_graph, - SizeTVec2D node_alignments, std::vector node_coverage_counts, - SizeTVec2D outgoing_edges, Uint16Vec3D outgoing_edges_coverage = {}) + SortedGraph(std::vector nodes, std::vector sorted_graph, + Int16Vec2D node_alignments, std::vector node_coverage_counts, + Int16Vec2D outgoing_edges, Uint16Vec3D outgoing_edges_coverage = {}) : BasicGraph(nodes, outgoing_edges, node_alignments, node_coverage_counts, outgoing_edges_coverage) , sorted_graph_(sorted_graph) { @@ -53,16 +53,16 @@ class SortedGraph : public BasicGraph } SortedGraph() = delete; - void get_node_id_to_pos(SizeT* node_id_to_pos) const + void get_node_id_to_pos(int16_t* node_id_to_pos) const { - for (int32_t pos = 0; pos < get_size(sorted_graph_); pos++) + for (int16_t pos = 0; pos < get_size(sorted_graph_); pos++) { int32_t id = sorted_graph_[pos]; - node_id_to_pos[id] = static_cast(pos); + node_id_to_pos[id] = pos; } } - void get_sorted_graph(SizeT* graph) const + void get_sorted_graph(int16_t* graph) const { for (int i = 0; i < get_size(sorted_graph_); i++) { @@ -71,7 +71,7 @@ class SortedGraph : public BasicGraph } protected: - std::vector sorted_graph_; + std::vector sorted_graph_; }; } // namespace cudapoa diff --git a/pygenomeworks/bin/alignment_visualizer b/pygenomeworks/bin/alignment_visualizer new file mode 100755 index 000000000..f62998dd2 --- /dev/null +++ b/pygenomeworks/bin/alignment_visualizer @@ -0,0 +1,133 @@ +#!/usr/bin/env python3 + +# +# Copyright 2020 NVIDIA CORPORATION. +# +# Licensed under the Apache License, Version 2.0 (the "License"); +# you may not use this file except in compliance with the License. +# You may obtain a copy of the License at +# +# http://www.apache.org/licenses/LICENSE-2.0 +# +# Unless required by applicable law or agreed to in writing, software +# distributed under the License is distributed on an "AS IS" BASIS, +# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +# See the License for the specific language governing permissions and +# limitations under the License. +# + +"""Tool to visualize pairwise alignments.""" + +import argparse +import numpy as np +import matplotlib.pyplot as plt +import csv +import math + + +def expand_cigar(cigar): + """ + Expand CIGAR string into array of CIGAR operations. + """ + start_of_num = 0 + str_idx = 0 + expanded_cigar = [] + for c in cigar: + if c.isdigit(): + str_idx += 1 + else: + temp_arr = [c] * int(cigar[start_of_num: str_idx]) + expanded_cigar.extend(temp_arr) + str_idx += 1 + start_of_num = str_idx + return expanded_cigar + + +def fill_alignment_matrix_with_cigar(alignment_matrix, cigar, val): + """ + Based on CIGAR string, fill backtrce matrix with alignment + path, storing value val at each cell. + """ + # Starting the alignment at top left of matrix + i = 0 + j = 0 + alignment_matrix[i, j] = val + + cigar = expand_cigar(cigar) + for op in cigar: + if op == 'M': + i += 1 + j += 1 + alignment_matrix[i, j] = val + elif op == 'I': + i += 0 + j += 1 + alignment_matrix[i, j] = val + elif op == 'D': + i += 1 + j += 0 + alignment_matrix[i, j] = val + else: + raise RuntimeError(f"Unknown operation type - {op}") + + +def viz_alignments(axes, target, query, cigars): + """ + Visualize alignment(s) between target and query on the + subplot defined by axes. Supports rendering multiple + alignments per pair. + """ + target = list(target) + query = list(query) + + alignment_matrix = np.zeros((len(query) + 1, len(target) + 1)) + for i, cigar in enumerate(cigars): + fill_alignment_matrix_with_cigar(alignment_matrix, cigar, i+1) + + cax = axes.matshow(alignment_matrix) + figure.colorbar(cax) + + target = [''] * 2 + target + query = [''] * 2 + query + axes.set_xticklabels(target) + axes.set_yticklabels(query) + + +def parse_args(): + parser = argparse.ArgumentParser(description="A tool to visualize alignment for pairwise alignments.") + parser.add_argument("alignment_file", + help="A CSV file of the format target,query,cigar1,cigar2,...", + type=str) + args = parser.parse_args() + return args + + +if __name__ == "__main__": + targets = [] + queries = [] + cigars = [] + + # Parse arguments + args = parse_args() + + # Parse in all alignments to be visualized. + with open(args.alignment_file, newline='') as fh: + reader = csv.reader(fh) + for row in reader: + targets.append(row[0]) + queries.append(row[1]) + cigars.append(row[2:]) + + # Generate figure dimensions. + plot_width = int(math.sqrt(len(targets))) + 1 + plot_height = (len(targets) // plot_width) + 1 + + # Iterate through every pair of alignment and visualize it. + figure = plt.figure() + for i in range(len(targets)): + subplot_idx = i + 1 + subplot = figure.add_subplot(plot_width, plot_height, subplot_idx) + viz_alignments(subplot, targets[i], queries[i], cigars[i]) + + # Generate final plot. + plt.show() diff --git a/pygenomeworks/bin/evaluate_paf b/pygenomeworks/bin/evaluate_paf index b29aacbd1..52a5be034 100755 --- a/pygenomeworks/bin/evaluate_paf +++ b/pygenomeworks/bin/evaluate_paf @@ -30,9 +30,11 @@ from genomeworks.io import pafio def points_equal(fixed, point, slop): return max(0, int(fixed) - slop) <= int(point) <= (int(fixed) + slop) + def within(val, target, tolerance=0.05): return abs(float(val) - float(target)) <= tolerance + def calculate_reciprocal_overlap(record, other): q_overlap = min(record.query_end, other.query_end) - max(record.query_start, other.query_start) q_total_len = max(record.query_start, other.query_start) - min(record.query_start, other.query_start) @@ -46,6 +48,7 @@ def calculate_reciprocal_overlap(record, other): def _gen_interval(start, end, value, tolerance): return intervaltree.Interval(max(0, int(start) - tolerance), end + tolerance, value) + def construct_interval_dictionaries(paf_record_list, tolerance): """ Constructs a dictionary[string->IntervalTree], where the keys of the dictionary are @@ -64,6 +67,7 @@ def construct_interval_dictionaries(paf_record_list, tolerance): return query_paf_dict, target_paf_dict + def records_equal(record, other, pos_tolerance): query_start_valid = points_equal(record.query_start, other.query_start, pos_tolerance) query_end_valid = points_equal(record.query_end, other.query_end, pos_tolerance) @@ -76,6 +80,7 @@ def records_equal(record, other, pos_tolerance): return equal, query_start_valid, query_end_valid, target_start_valid, target_end_valid, strands_equal + def match_overlaps(record, other, pos_tolerance, min_reciprocal_overlap): """Given two sets of query and target ranges, check if the query and target ranges fall within a specified tolerance of each other. @@ -89,9 +94,10 @@ def match_overlaps(record, other, pos_tolerance, min_reciprocal_overlap): Returns: Boolean indicating query and target match. """ - equal, query_start_valid, query_end_valid, target_start_valid, target_end_valid, strands_equal = records_equal(record, other, pos_tolerance) - - reciprocal = calculate_reciprocal_overlap(record, other) > min_reciprocal_overlap + equal, query_start_valid, query_end_valid, target_start_valid, target_end_valid, \ + strands_equal = records_equal(record, other, pos_tolerance) + pct_recip = calculate_reciprocal_overlap(record, other) + reciprocal = pct_recip > min_reciprocal_overlap match = equal or reciprocal @@ -100,8 +106,9 @@ def match_overlaps(record, other, pos_tolerance, min_reciprocal_overlap): "target_start_valid": target_start_valid, "target_end_valid": target_end_valid, "reciprocal_overlaps": reciprocal, - "strands_equal" : strands_equal, - "equal" : equal, + "percent_reciprocal": pct_recip, + "strands_equal": strands_equal, + "equal": equal, "match": match} return match @@ -117,16 +124,31 @@ def generate_key(name_1, name_2): """ return "{}_{}".format(name_1, name_2) + def _swap(val, dest): return dest, val + def reverse_record(record): query_sequence_name, target_sequence_name = _swap(record.query_sequence_name, record.target_sequence_name) query_sequence_length, target_sequence_length = _swap(record.query_sequence_length, record.target_sequence_length) query_start, target_start = _swap(record.query_start, record.target_start) query_end, target_end = _swap(record.query_end, record.target_end) - return pafio.Overlap(query_sequence_name, query_sequence_length, query_start, query_end, record.relative_strand, target_sequence_name, target_sequence_length, target_start, target_end, record.num_residue_matches, record.alignment_block_length, record.mapping_quality, record.tags) + return pafio.Overlap(query_sequence_name, + query_sequence_length, + query_start, + query_end, + record.relative_strand, + target_sequence_name, + target_sequence_length, + target_start, + target_end, + record.num_residue_matches, + record.alignment_block_length, + record.mapping_quality, + record.tags) + def evaluate_paf(truth_paf_filepath, test_paf_filepath, pos_tolerance, min_reciprocal, skip_self_mappings=True): """Given a truth and test set PAF file, count number of in/incorrectly detected, and non-detected overlaps @@ -163,8 +185,6 @@ def evaluate_paf(truth_paf_filepath, test_paf_filepath, pos_tolerance, min_recip test_overlap_count = 0 print("{} true overlaps in truth set".format(num_true_overlaps)) - seen_test_overlap_keys = set() - incorrect_query_start = 0 incorrect_query_end = 0 incorrect_target_start = 0 @@ -175,68 +195,81 @@ def evaluate_paf(truth_paf_filepath, test_paf_filepath, pos_tolerance, min_recip (test_overlap.query_sequence_name == test_overlap.target_sequence_name): continue test_overlap_count += 1 - # query_0 = (test_overlap.query_start, test_overlap.query_end) - # target_0 = (test_overlap.target_start, test_overlap.target_end) key = generate_key(test_overlap.query_sequence_name, test_overlap.target_sequence_name) key_reversed = generate_key(test_overlap.target_sequence_name, test_overlap.query_sequence_name) - # if (key in seen_test_overlap_keys) or (key_reversed in seen_test_overlap_keys): - # continue - - # seen_test_overlap_keys.add(key) - # seen_test_overlap_keys.add(key_reversed) + best_pct_match = 0.0 + best_ends = [1, 1, 1, 1] found_match = False if key in truth_keys: for truth_interval in truth_query_intervals[test_overlap.query_sequence_name]: truth_overlap = truth_interval.data match_statistics = match_overlaps(truth_overlap, test_overlap, pos_tolerance, min_reciprocal) - incorrect_query_start += not match_statistics["query_start_valid"] - incorrect_query_end += not match_statistics["query_end_valid"] - incorrect_target_start += not match_statistics["target_start_valid"] - incorrect_target_end += not match_statistics["target_end_valid"] if match_statistics["match"]: true_positive_count += 1 found_match = True + best_pct_match = match_statistics["percent_reciprocal"] + best_ends = [0, 0, 0, 0] break + pct_match = match_statistics["percent_reciprocal"] + if pct_match > best_pct_match: + best_pct_match = pct_match + best_ends[0] = 1 if not match_statistics["query_start_valid"] else 0 + best_ends[1] = 1 if not match_statistics["query_end_valid"] else 0 + best_ends[2] = 1 if not match_statistics["target_start_valid"] else 0 + best_ends[3] = 1 if not match_statistics["target_end_valid"] else 0 if not found_match: for truth_interval in truth_target_intervals[test_overlap.target_sequence_name]: truth_overlap = truth_interval.data match_statistics = match_overlaps(truth_overlap, test_overlap, pos_tolerance, min_reciprocal) - incorrect_query_start += not match_statistics["query_start_valid"] - incorrect_query_end += not match_statistics["query_end_valid"] - incorrect_target_start += not match_statistics["target_start_valid"] - incorrect_target_end += not match_statistics["target_end_valid"] if match_statistics["match"]: true_positive_count += 1 found_match = True break + pct_match = match_statistics["percent_reciprocal"] + if pct_match > best_pct_match: + best_pct_match = pct_match + best_ends[0] = 1 if not match_statistics["query_start_valid"] else 0 + best_ends[1] = 1 if not match_statistics["query_end_valid"] else 0 + best_ends[2] = 1 if not match_statistics["target_start_valid"] else 0 + best_ends[3] = 1 if not match_statistics["target_end_valid"] else 0 if not found_match and key_reversed in truth_keys: test_overlap = reverse_record(test_overlap) for truth_interval in truth_query_intervals[key_reversed]: truth_overlap = truth_interval.data match_statistics = match_overlaps(truth_overlap, test_overlap) - incorrect_query_start += not match_statistics["query_start_valid"] - incorrect_query_end += not match_statistics["query_end_valid"] - incorrect_target_start += not match_statistics["target_start_valid"] - incorrect_target_end += not match_statistics["target_end_valid"] if match_statistics["match"]: true_positive_count += 1 found_match = True break + pct_match = match_statistics["percent_reciprocal"] + if pct_match > best_pct_match: + best_pct_match = pct_match + best_ends[0] = 1 if not match_statistics["query_start_valid"] else 0 + best_ends[1] = 1 if not match_statistics["query_end_valid"] else 0 + best_ends[2] = 1 if not match_statistics["target_start_valid"] else 0 + best_ends[3] = 1 if not match_statistics["target_end_valid"] else 0 if not found_match: for truth_interval in truth_target_intervals[key_reversed]: truth_overlap = truth_interval.data match_statistics = match_overlaps(truth_overlap, test_overlap) - incorrect_query_start += not match_statistics["query_start_valid"] - incorrect_query_end += not match_statistics["query_end_valid"] - incorrect_target_start += not match_statistics["target_start_valid"] - incorrect_target_end += not match_statistics["target_end_valid"] if match_statistics["match"]: true_positive_count += 1 found_match = True break + pct_match = match_statistics["percent_reciprocal"] + if pct_match > best_pct_match: + best_pct_match = pct_match + best_ends[0] = 1 if not match_statistics["query_start_valid"] else 0 + best_ends[1] = 1 if not match_statistics["query_end_valid"] else 0 + best_ends[2] = 1 if not match_statistics["target_start_valid"] else 0 + best_ends[3] = 1 if not match_statistics["target_end_valid"] else 0 + incorrect_query_start += best_ends[0] + incorrect_query_end += best_ends[1] + incorrect_target_start += best_ends[2] + incorrect_target_end += best_ends[3] if not found_match: false_positive_count += 1 @@ -267,21 +300,23 @@ if __name__ == "__main__": parser.add_argument("-s", '--slop', dest="pos_tolerance", type=int, default=200, - help="Number of basepairs to tolerate on either side of an interval (or record) to consider the two records equal [200].") + help="Number of basepairs to tolerate on either side of an interval (or record) \ + to consider the two records equal [200].") parser.add_argument("-r", "--reciprocal-cutoff", dest="min_reciprocal", type=float, - required=False, default=0.9, help="Amount of reciprocal overlap required to consider two overlaps the same [0.9]") + required=False, default=0.9, help="Amount of reciprocal overlap required \ + to consider two overlaps the same [0.9]") parser.add_argument('--skip_self_mapping', action="store_true", help="Skip checking overlaps where query/target name are same") args = parser.parse_args() - true_positives, false_positives, false_negatives, incorrect_query_start, incorrect_query_end, incorrect_target_start, \ - incorrect_target_end, total_test_records = evaluate_paf(args.truth, - args.test, - args.pos_tolerance, - args.min_reciprocal, - args.skip_self_mapping) + true_positives, false_positives, false_negatives, incorrect_query_start, incorrect_query_end, \ + incorrect_target_start, incorrect_target_end, total_test_records = evaluate_paf(args.truth, + args.test, + args.pos_tolerance, + args.min_reciprocal, + args.skip_self_mapping) print("Total test records:", total_test_records) print("True positives: ", true_positives) print("False positives: ", false_positives) diff --git a/pygenomeworks/genomeworks/cuda/cuda.pxd b/pygenomeworks/genomeworks/cuda/cuda.pxd new file mode 100644 index 000000000..f8bf69850 --- /dev/null +++ b/pygenomeworks/genomeworks/cuda/cuda.pxd @@ -0,0 +1,29 @@ +# +# Copyright 2019-2020 NVIDIA CORPORATION. +# +# Licensed under the Apache License, Version 2.0 (the "License"); +# you may not use this file except in compliance with the License. +# You may obtain a copy of the License at +# +# http://www.apache.org/licenses/LICENSE-2.0 +# +# Unless required by applicable law or agreed to in writing, software +# distributed under the License is distributed on an "AS IS" BASIS, +# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. +# See the License for the specific language governing permissions and +# limitations under the License. +# + +# cython: profile=False +# distutils: language = c++ +# cython: embedsignature = True +# cython: language_level = 3 + +# This file declares public cython utility objects for CUDA. + +cdef class CudaStream: + # Using size_t to store stream since underlying + # representation of cudaStream_t is a (void *) + # and python doesn't know how to deal with converting + # (void *) to python objects. + cdef size_t stream diff --git a/pygenomeworks/genomeworks/cuda/cuda.pyx b/pygenomeworks/genomeworks/cuda/cuda.pyx index e330823c6..32396238f 100644 --- a/pygenomeworks/genomeworks/cuda/cuda.pyx +++ b/pygenomeworks/genomeworks/cuda/cuda.pyx @@ -39,12 +39,6 @@ cdef class CudaStream: """Class to abstract the usage of CUDA streams which enable easy asynchronous execution of CUDA kernels. """ - # Using size_t to store stream since underlying - # representation of cudaStream_t is a (void *) - # and python doesn't know how to deal with converting - # (void *) to python objects. - cdef size_t stream - def __cinit__(self): """Constructs a CudaStream object to encapsulate a CUDA stream. """ diff --git a/pygenomeworks/genomeworks/cudaaligner/cudaaligner.pyx b/pygenomeworks/genomeworks/cudaaligner/cudaaligner.pyx index 967395e4e..88fa820ca 100644 --- a/pygenomeworks/genomeworks/cudaaligner/cudaaligner.pyx +++ b/pygenomeworks/genomeworks/cudaaligner/cudaaligner.pyx @@ -22,7 +22,6 @@ """Bindings for CUDAALIGNER.""" -import genomeworks.cuda as cuda from cython.operator cimport dereference as deref from libcpp.vector cimport vector @@ -30,7 +29,9 @@ from libcpp.memory cimport unique_ptr, shared_ptr from libcpp.string cimport string from libc.stdint cimport uint16_t +from cpython.ref cimport Py_INCREF, Py_DECREF from genomeworks.cuda.cuda_runtime_api cimport _Stream +from genomeworks.cuda.cuda cimport CudaStream cimport genomeworks.cudaaligner.cudaaligner as cudaaligner @@ -129,7 +130,7 @@ cdef class CudaAlignerBatch: """Python API for CUDA-accelerated sequence to sequence alignment. """ cdef unique_ptr[cudaaligner.Aligner] aligner - cdef public object stream + cdef public CudaStream stream def __cinit__( self, @@ -160,12 +161,18 @@ cdef class CudaAlignerBatch: cdef _Stream temp_stream if (stream is None): temp_stream = NULL - elif (not isinstance(stream, cuda.CudaStream)): + elif (not isinstance(stream, CudaStream)): raise RuntimeError("Type for stream option must be CudaStream") else: st = stream.stream temp_stream = <_Stream>st - self.stream = stream # keep a reference to the stream, such that it gets destroyed after the aligner. + # keep a reference to the stream, such that it gets destroyed after the aligner. + self.stream = stream + # Increasing ref count of CudaStream object to ensure it doesn't get garbage + # collected before CudaAlignerBatch object. + # NOTE: Ideally this is taken care of by just storing the reference + # in the line above, but that doesn't seem to be persistent. + Py_INCREF(stream) cdef cudaaligner.AlignmentType alignment_type_enum if (alignment_type == "global"): @@ -268,6 +275,8 @@ cdef class CudaAlignerBatch: def __dealloc__(self): self.aligner.reset() + # Decreasing ref count for CudaStream object. + Py_DECREF(self.stream) def reset(self): """Reset the contents of the batch so the same GPU memory can be used to diff --git a/pygenomeworks/genomeworks/cudapoa/cudapoa.pxd b/pygenomeworks/genomeworks/cudapoa/cudapoa.pxd index bed26a4bb..5f7f5bcbc 100644 --- a/pygenomeworks/genomeworks/cudapoa/cudapoa.pxd +++ b/pygenomeworks/genomeworks/cudapoa/cudapoa.pxd @@ -47,7 +47,8 @@ cdef extern from "claraparabricks/genomeworks/cudapoa/cudapoa.hpp" namespace "cl exceeded_maximum_sequences_per_poa node_count_exceeded_maximum_graph_size edge_count_exceeded_maximum_graph_size - seq_len_exceeded_maximum_nodes_per_window + exceeded_adaptive_banded_matrix_size + exceeded_maximum_predecessor_distance loop_count_exceeded_upper_bound output_type_unavailable generic_error @@ -74,17 +75,14 @@ cdef extern from "claraparabricks/genomeworks/cudapoa/batch.hpp" namespace "clar int32_t max_sequence_size int32_t max_consensus_size int32_t max_nodes_per_graph - int32_t max_nodes_per_graph_banded - int32_t max_matrix_graph_dimension - int32_t max_matrix_graph_dimension_banded - int32_t max_matrix_sequence_dimension + int32_t matrix_sequence_dimension int32_t alignment_band_width int32_t max_sequences_per_poa BandMode band_mode - BatchConfig(int32_t, int32_t, int32_t, BandMode) - BatchConfig(int32_t, int32_t, int32_t, - int32_t, int32_t, int32_t, BandMode) + BatchConfig(int32_t, int32_t, int32_t, BandMode, float, float, int32t_t) + BatchConfig(int32_t, int32_t, int32_t, int32_t, + int32_t, int32_t, BandMode, int32_t) ctypedef vector[Entry] Group diff --git a/pygenomeworks/genomeworks/cudapoa/cudapoa.pyx b/pygenomeworks/genomeworks/cudapoa/cudapoa.pyx index e7051493d..8d52f5061 100644 --- a/pygenomeworks/genomeworks/cudapoa/cudapoa.pyx +++ b/pygenomeworks/genomeworks/cudapoa/cudapoa.pyx @@ -24,8 +24,6 @@ import networkx as nx -import genomeworks.cuda as cuda - from cython.operator cimport dereference as deref from libc.stdint cimport uint16_t, int8_t, int32_t from libcpp.memory cimport unique_ptr, make_unique @@ -33,7 +31,9 @@ from libcpp.pair cimport pair from libcpp.string cimport string from libcpp.vector cimport vector +from cpython.ref cimport Py_INCREF, Py_DECREF from genomeworks.cuda.cuda_runtime_api cimport _Stream +from genomeworks.cuda.cuda cimport CudaStream from genomeworks.cudapoa.graph cimport DirectedGraph cimport genomeworks.cudapoa.cudapoa as cudapoa @@ -52,8 +52,10 @@ def status_to_str(status): return "node_count_exceeded_maximum_graph_size" elif status == cudapoa.edge_count_exceeded_maximum_graph_size: return "edge_count_exceeded_maximum_graph_size" - elif status == cudapoa.seq_len_exceeded_maximum_nodes_per_window: - return "seq_len_exceeded_maximum_nodes_per_window" + elif status == cudapoa.exceeded_adaptive_banded_matrix_size: + return "exceeded_adaptive_banded_matrix_size" + elif status == cudapoa.exceeded_maximum_predecessor_distance: + return "exceeded_maximum_predecessor_distance" elif status == cudapoa.loop_count_exceeded_upper_bound: return "loop_count_exceeded_upper_bound" elif status == cudapoa.output_type_unavailable: @@ -68,6 +70,7 @@ cdef class CudaPoaBatch: """Python API for CUDA-accelerated partial order alignment algorithm.""" cdef unique_ptr[cudapoa.Batch] batch cdef unique_ptr[cudapoa.BatchConfig] batch_size + cdef CudaStream stream def __cinit__( self, @@ -109,11 +112,18 @@ cdef class CudaPoaBatch: cdef _Stream temp_stream if (stream is None): temp_stream = NULL - elif (not isinstance(stream, cuda.CudaStream)): + elif (not isinstance(stream, CudaStream)): raise RuntimeError("Type for stream option must be CudaStream") else: st = stream.stream temp_stream = <_Stream>st + # keep a reference to the stream, such that it gets destroyed after the batch. + self.stream = stream + # Increasing ref count of CudaStream object to ensure it doesn't get garbage + # collected before CudaPoaBatch object. + # NOTE: Ideally this is taken care of by just storing the reference + # in the line above, but that doesn't seem to be persistent. + Py_INCREF(stream) if (output_type == "consensus"): output_mask = cudapoa.consensus @@ -129,28 +139,30 @@ cdef class CudaPoaBatch: cdef int32_t mx_seq_per_poa = max_sequences_per_poa cdef int32_t mx_consensus_sz = \ 2 * max_sequence_size if max_consensus_size is None else max_consensus_size - cdef int32_t mx_nodes_per_w + cdef int32_t mx_nodes_per_poa cdef int32_t matrix_seq_dim + cdef int32_t mx_pred_dist cdef BandMode batch_band_mode if (band_mode == "full_band"): batch_band_mode = BandMode.full_band - mx_nodes_per_w = 3 * max_sequence_size if max_nodes_per_graph is None else max_nodes_per_graph + mx_nodes_per_poa = 3 * max_sequence_size if max_nodes_per_graph is None else max_nodes_per_graph matrix_seq_dim = max_sequence_size if matrix_sequence_dimension is None else matrix_sequence_dimension elif (band_mode == "static_band"): batch_band_mode = BandMode.static_band - mx_nodes_per_w = 4 * max_sequence_size if max_nodes_per_graph is None else max_nodes_per_graph + mx_nodes_per_poa = 4 * max_sequence_size if max_nodes_per_graph is None else max_nodes_per_graph matrix_seq_dim = ((alignment_band_width + 8) if matrix_sequence_dimension is None else matrix_sequence_dimension) elif (band_mode == "adaptive_band"): batch_band_mode = BandMode.adaptive_band - mx_nodes_per_w = 4 * max_sequence_size if max_nodes_per_graph is None else max_nodes_per_graph + mx_nodes_per_poa = 4 * max_sequence_size if max_nodes_per_graph is None else max_nodes_per_graph matrix_seq_dim = (2*(alignment_band_width + 8) if matrix_sequence_dimension is None else matrix_sequence_dimension) else: raise RuntimeError("Unknown band_mode provided. Must be full_band/static_band/adaptive_band.") self.batch_size = make_unique[cudapoa.BatchConfig]( - mx_seq_sz, mx_consensus_sz, mx_nodes_per_w, band_width_sz, mx_seq_per_poa, matrix_seq_dim, batch_band_mode) + mx_seq_sz, mx_consensus_sz, mx_nodes_per_poa, band_width_sz, mx_seq_per_poa, matrix_seq_dim, + batch_band_mode, mx_pred_dist) self.batch = cudapoa.create_batch( device_id, @@ -314,3 +326,9 @@ cdef class CudaPoaBatch: assigned to batch object. """ deref(self.batch).reset() + + def __dealloc__(self): + # Decreasing ref count for CudaStream object. + self.batch.reset() + self.batch_size.reset() + Py_DECREF(self.stream) diff --git a/pygenomeworks/requirements.txt b/pygenomeworks/requirements.txt index 61e0674b5..2413134dd 100644 --- a/pygenomeworks/requirements.txt +++ b/pygenomeworks/requirements.txt @@ -18,6 +18,7 @@ Cython==0.29.12 intervaltree==3.1.0 +matplotlib==3.3.2 networkx==2.4 numpy==1.16.3 pytest==4.4.1 diff --git a/pygenomeworks/setup_pygenomeworks.py b/pygenomeworks/setup_pygenomeworks.py index 4e88437ba..a46bd2f6c 100644 --- a/pygenomeworks/setup_pygenomeworks.py +++ b/pygenomeworks/setup_pygenomeworks.py @@ -83,7 +83,8 @@ def _run_cmake_cmd(self): cmake_args = ['-DCMAKE_INSTALL_PREFIX=' + self.gw_install_dir, '-DCMAKE_BUILD_TYPE=' + 'Release', '-DCMAKE_INSTALL_RPATH=' + os.path.join(self.gw_install_dir, "lib"), - '-Dgw_generate_docs=OFF'] + '-Dgw_generate_docs=OFF', + '-Dgw_cuda_gen_all_arch=ON'] cmake_args += [self.cmake_extra_args] if self.cmake_extra_args else [] if self.cuda_toolkit_root_dir: diff --git a/pygenomeworks/style_check b/pygenomeworks/style_check index 5ef962dd5..a4bc28e33 100755 --- a/pygenomeworks/style_check +++ b/pygenomeworks/style_check @@ -23,6 +23,7 @@ set -e PYGW_DIR=$(dirname "$(readlink -f "${BASH_SOURCE[0]}")") echo "Run Python formatting check..." flake8 "$PYGW_DIR" +flake8 "$PYGW_DIR" $PYGW_DIR/bin/* echo "Run Cython formatting check..." flake8 "$PYGW_DIR" --config "$PYGW_DIR"/.flake8.cython echo "Run Python docstring conventions check..." diff --git a/pygenomeworks/test/test_cudaaligner_bindings.py b/pygenomeworks/test/test_cudaaligner_bindings.py index 42f1c0369..ecdc17d39 100644 --- a/pygenomeworks/test/test_cudaaligner_bindings.py +++ b/pygenomeworks/test/test_cudaaligner_bindings.py @@ -23,13 +23,6 @@ from genomeworks.simulators.readsim import NoisyReadSimulator -@pytest.fixture -def get_stream(): - stream = cuda.CudaStream() - yield stream - del stream - - @pytest.mark.gpu @pytest.mark.parametrize("query, target, cigar", [ ("AAAAAAA", "TTTTTTT", "7M"), @@ -38,11 +31,11 @@ def get_stream(): ("TGCA", "ATACGCT", "1I1M2I3M"), pytest.param("ACGT", "TCGA", "5M", marks=pytest.mark.xfail), ]) -def test_cudaaligner_simple_batch(query, target, cigar, get_stream): +def test_cudaaligner_simple_batch(query, target, cigar): """Test valid calculation of alignments by checking cigar strings. """ device = cuda.cuda_get_device() - stream = get_stream + stream = cuda.CudaStream() batch = CudaAlignerBatch(len(query), len(target), 1, alignment_type="global", stream=stream, device_id=device) batch.add_alignment(query, target) batch.align_all()