Merge branch 'development'

# Conflicts:
#	exomiser-cli/pom.xml
#	exomiser-cli/src/main/resources/examples/NA19722_252900_AR_SGSH_1_NONSYNONYMOUS.yml
#	exomiser-cli/src/main/resources/examples/NA19722_601952_AUTOSOMAL_RECESSIVE_POMP_13_29233225_5UTR_38.yml
#	exomiser-cli/src/main/resources/examples/test-analysis-exome.yml
#	exomiser-cli/src/main/resources/examples/test-analysis-genome.yml
#	exomiser-cli/src/main/resources/examples/test-analysis-multisample.yml
#	exomiser-core/pom.xml
#	exomiser-data-genome/pom.xml
#	exomiser-data-phenotype/pom.xml
#	exomiser-rest-analysis/pom.xml
#	exomiser-rest-prioritiser/pom.xml
#	exomiser-spring-boot-autoconfigure/pom.xml
#	exomiser-spring-boot-starter/pom.xml
#	exomiser-spring-boot-test/pom.xml
#	exomiser-web/pom.xml
#	pom.xml

.circleci/config.yml

@@ -0,0 +1,37 @@
+version: 2
+jobs:
+  build:
+    working_directory: ~/exomiser
+    environment:
+      CIRCLE_ARTIFACTS: /tmp/circleci-artifacts
+      CIRCLE_TEST_REPORTS: /tmp/circleci-test-results
+    docker:
+      - image: circleci/openjdk:8-jdk
+    steps:
+      - checkout
+      - run: chmod +x mvnw
+      - restore_cache:
+          key: exomiser-{{ checksum "pom.xml" }}
+      - run: ./mvnw clean install -DskipTests=true -Dmaven.javadoc.skip=true -B -V
+      - save_cache:
+          paths:
+            - ~/.m2
+          key: exomiser-{{ checksum "pom.xml" }}
+      - run: ./mvnw test -B
+      - run: ./mvnw sonar:sonar -Dsonar.host.url=https://sonarcloud.io -Dsonar.login=$SONAR_TOKEN
+      #Save junit xml
+      - run: mkdir -p $CIRCLE_TEST_REPORTS/junit/
+      - run: find . -type f -regex ".*/target/surefire-reports/.*xml" -exec cp {} $CIRCLE_TEST_REPORTS/ \;
+      #Save jars
+      - run: mkdir -p $CIRCLE_ARTIFACTS/
+      - run: find . -type f -regex ".*/target/exomiser.*jar" -exec cp {} $CIRCLE_ARTIFACTS/ \;
+      - run: find . -type f -regex ".*/target/exomiser.*zip" -exec cp {} $CIRCLE_ARTIFACTS/ \;
+      # Save test results
+      - store_test_results:
+          path: /tmp/circleci-test-results
+      # Save artifacts
+      - store_artifacts:
+          path: /tmp/circleci-artifacts
+      - store_artifacts:
+          path: /tmp/circleci-test-results
+      - run: bash <(curl -s https://codecov.io/bash)

.mvn/wrapper/maven-wrapper.properties

@@ -1 +1 @@
-distributionUrl=https://repo1.maven.org/maven2/org/apache/maven/apache-maven/3.5.0/apache-maven-3.5.0-bin.zip
+distributionUrl=https://repo1.maven.org/maven2/org/apache/maven/apache-maven/3.5.2/apache-maven-3.5.2-bin.zip

README.md

@@ -3,17 +3,16 @@ The Exomiser - A Tool to Annotate and Prioritize Exome Variants
 
 [![GitHub release](https://img.shields.io/github/release/exomiser/Exomiser.svg)](https://github.com/exomiser/Exomiser/releases)
 [![CircleCI](https://circleci.com/gh/exomiser/Exomiser/tree/development.svg?style=shield)](https://circleci.com/gh/exomiser/Exomiser/tree/development)
-[![Codacy Badge](https://api.codacy.com/project/badge/Grade/041e1de03278443c9eb64900b839e7ac)](https://www.codacy.com/app/jules-jacobsen/Exomiser?utm_source=github.com&utm_medium=referral&utm_content=exomiser/Exomiser&utm_campaign=Badge_Grade)
-
+[![Codacy Badge](https://api.codacy.com/project/badge/Grade/b518a9448b5b4889a40b3dc660ef585a)](https://www.codacy.com/app/monarch-initiative/Exomiser?utm_source=github.com&utm_medium=referral&utm_content=exomiser/Exomiser&utm_campaign=Badge_Grade)
 #### Overview:
 
 The Exomiser is a Java program that finds potential disease-causing variants from whole-exome or whole-genome sequencing data.
 
-Starting from a VCF file and a set of phenotypes encoded using the [Human Phenotype Ontology](http://www.human-phenotype-ontology.org) (HPO) it will annotate, filter and prioritise likely causative variants. The program does this based on user-defined criteria such as a variant's predicted pathogenicity, frequency of occurrence in a population and also how closely the given phenotype matches the known phenotype of diseased genes from human and model organism data.
+Starting from a [VCF](https://samtools.github.io/hts-specs/VCFv4.3.pdf) file and a set of phenotypes encoded using the [Human Phenotype Ontology](http://www.human-phenotype-ontology.org) (HPO) it will annotate, filter and prioritise likely causative variants. The program does this based on user-defined criteria such as a variant's predicted pathogenicity, frequency of occurrence in a population and also how closely the given phenotype matches the known phenotype of diseased genes from human and model organism data.
 
-The functional annotation of variants is handled by [Jannovar](https://github.com/charite/jannovar) and uses [UCSC](http://genome.ucsc.edu) KnownGene transcript definitions and hg19 genomic coordinates.
+The functional annotation of variants is handled by [Jannovar](https://github.com/charite/jannovar) and uses any of [UCSC](http://genome.ucsc.edu), [RefSeq](https://www.ncbi.nlm.nih.gov/refseq/) or [Ensembl](https://www.ensembl.org/Homo_sapiens/Info/Index) KnownGene transcript definitions and hg19 or hg38 genomic coordinates.
 
-Variants are prioritised according to user-defined criteria on variant frequency, pathogenicity, quality, inheritance pattern, and model organism phenotype data. Predicted pathogenicity data is extracted from the [dbNSFP](http://www.ncbi.nlm.nih.gov/pubmed/21520341) resource. Variant frequency data is taken from the [1000 Genomes](http://www.1000genomes.org/), [ESP](http://evs.gs.washington.edu/EVS) and [ExAC](http://exac.broadinstitute.org) datasets. Subsets of these frequency and pathogenicity data can be defined to further tune the analysis. Cross-species phenotype comparisons come from our PhenoDigm tool powered by the OWLTools [OWLSim](https://github.com/owlcollab/owltools) algorithm.
+Variants are prioritised according to user-defined criteria on variant frequency, pathogenicity, quality, inheritance pattern, and model organism phenotype data. Predicted pathogenicity data is extracted from the [dbNSFP](http://www.ncbi.nlm.nih.gov/pubmed/21520341) resource. Variant frequency data is taken from the [1000 Genomes](http://www.1000genomes.org/), [ESP](http://evs.gs.washington.edu/EVS), [TOPMed](http://www.uk10k.org/studies/cohorts.html), [UK10K](http://www.uk10k.org/studies/cohorts.html), [ExAC](http://exac.broadinstitute.org) and [gnomAD](http://gnomad.broadinstitute.org/) datasets. Subsets of these frequency and pathogenicity data can be defined to further tune the analysis. Cross-species phenotype comparisons come from our PhenoDigm tool powered by the OWLTools [OWLSim](https://github.com/owlcollab/owltools) algorithm.
 
 The Exomiser was developed by the Computational Biology and Bioinformatics group at the Institute for Medical Genetics and Human Genetics of the Charité - Universitätsmedizin Berlin, the Mouse Informatics Group at the Sanger Institute and other members of the [Monarch initiative](https://monarchinitiative.org).
 
@@ -87,7 +86,7 @@ private final Exomiser exomiser;
                 .probandSampleName(probandSampleId)
                 .hpoIds(phenotypes)
                 .analysisMode(AnalysisMode.PASS_ONLY)
-                .modeOfInheritance(ModeOfInheritance.AUTOSOMAL_DOMINANT)
+                .modeOfInheritance(EnumSet.of(ModeOfInheritance.AUTOSOMAL_DOMINANT, ModeOfInheritance.AUTOSOMAL_RECESSIVE))
                 .frequencySources(FrequencySource.ALL_EXTERNAL_FREQ_SOURCES)
                 .pathogenicitySources(EnumSet.of(PathogenicitySource.POLYPHEN, PathogenicitySource.MUTATION_TASTER, PathogenicitySource.SIFT))
                 .addPhivePrioritiser()

docs/Makefile

@@ -0,0 +1,20 @@
+# Minimal makefile for Sphinx documentation
+#
+
+# You can set these variables from the command line.
+SPHINXOPTS    =
+SPHINXBUILD   = sphinx-build
+SPHINXPROJ    = exomiser
+SOURCEDIR     = .
+BUILDDIR      = .build
+
+# Put it first so that "make" without argument is like "make help".
+help:
+	@$(SPHINXBUILD) -M help "$(SOURCEDIR)" "$(BUILDDIR)" $(SPHINXOPTS) $(O)
+
+.PHONY: help Makefile
+
+# Catch-all target: route all unknown targets to Sphinx using the new
+# "make mode" option.  $(O) is meant as a shortcut for $(SPHINXOPTS).
+%: Makefile
+	@$(SPHINXBUILD) -M $@ "$(SOURCEDIR)" "$(BUILDDIR)" $(SPHINXOPTS) $(O)

docs/conf.py

@@ -0,0 +1,180 @@
+# -*- coding: utf-8 -*-
+#
+# Configuration file for the Sphinx documentation builder.
+#
+# This file does only contain a selection of the most common options. For a
+# full list see the documentation:
+# http://www.sphinx-doc.org/en/stable/config
+
+# -- Path setup --------------------------------------------------------------
+
+# If extensions (or modules to document with autodoc) are in another directory,
+# add these directories to sys.path here. If the directory is relative to the
+# documentation root, use os.path.abspath to make it absolute, like shown here.
+#
+# import os
+# import sys
+# sys.path.insert(0, os.path.abspath('.'))
+
+
+# -- Project information -----------------------------------------------------
+
+project = u'exomiser'
+copyright = u'2018, Jules Jacobsen, Damian Smedley, Peter Robinson'
+author = u'Jules Jacobsen, Damian Smedley, Peter Robinson'
+
+# The short X.Y version
+version = u''
+# The full version, including alpha/beta/rc tags
+release = u'10.0.0'
+
+
+# -- General configuration ---------------------------------------------------
+
+# If your documentation needs a minimal Sphinx version, state it here.
+#
+# needs_sphinx = '1.0'
+
+# Add any Sphinx extension module names here, as strings. They can be
+# extensions coming with Sphinx (named 'sphinx.ext.*') or your custom
+# ones.
+extensions = [
+    'sphinx.ext.githubpages',
+]
+
+# Add any paths that contain templates here, relative to this directory.
+templates_path = ['.templates']
+
+# The suffix(es) of source filenames.
+# You can specify multiple suffix as a list of string:
+#
+# source_suffix = ['.rst', '.md']
+source_suffix = '.rst'
+
+# The master toctree document.
+master_doc = 'index'
+
+# The language for content autogenerated by Sphinx. Refer to documentation
+# for a list of supported languages.
+#
+# This is also used if you do content translation via gettext catalogs.
+# Usually you set "language" from the command line for these cases.
+language = None
+
+# List of patterns, relative to source directory, that match files and
+# directories to ignore when looking for source files.
+# This pattern also affects html_static_path and html_extra_path .
+exclude_patterns = [u'.build', 'Thumbs.db', '.DS_Store']
+
+# The name of the Pygments (syntax highlighting) style to use.
+pygments_style = 'sphinx'
+
+
+# -- Options for HTML output -------------------------------------------------
+
+# The theme to use for HTML and HTML Help pages.  See the documentation for
+# a list of builtin themes.
+#
+html_theme = 'alabaster'
+
+# Theme options are theme-specific and customize the look and feel of a theme
+# further.  For a list of options available for each theme, see the
+# documentation.
+#
+# html_theme_options = {}
+
+# Add any paths that contain custom static files (such as style sheets) here,
+# relative to this directory. They are copied after the builtin static files,
+# so a file named "default.css" will overwrite the builtin "default.css".
+html_static_path = ['.static']
+
+# Custom sidebar templates, must be a dictionary that maps document names
+# to template names.
+#
+# The default sidebars (for documents that don't match any pattern) are
+# defined by theme itself.  Builtin themes are using these templates by
+# default: ``['localtoc.html', 'relations.html', 'sourcelink.html',
+# 'searchbox.html']``.
+#
+# html_sidebars = {}
+
+
+# -- Options for HTMLHelp output ---------------------------------------------
+
+# Output file base name for HTML help builder.
+htmlhelp_basename = 'exomiserdoc'
+
+
+# -- Options for LaTeX output ------------------------------------------------
+
+latex_elements = {
+    # The paper size ('letterpaper' or 'a4paper').
+    #
+    # 'papersize': 'letterpaper',
+
+    # The font size ('10pt', '11pt' or '12pt').
+    #
+    # 'pointsize': '10pt',
+
+    # Additional stuff for the LaTeX preamble.
+    #
+    # 'preamble': '',
+
+    # Latex figure (float) alignment
+    #
+    # 'figure_align': 'htbp',
+}
+
+# Grouping the document tree into LaTeX files. List of tuples
+# (source start file, target name, title,
+#  author, documentclass [howto, manual, or own class]).
+latex_documents = [
+    (master_doc, 'exomiser.tex', u'exomiser Documentation',
+     u'Jules Jacobsen, Damian Smedley, Peter Robinson', 'manual'),
+]
+
+
+# -- Options for manual page output ------------------------------------------
+
+# One entry per manual page. List of tuples
+# (source start file, name, description, authors, manual section).
+man_pages = [
+    (master_doc, 'exomiser', u'exomiser Documentation',
+     [author], 1)
+]
+
+
+# -- Options for Texinfo output ----------------------------------------------
+
+# Grouping the document tree into Texinfo files. List of tuples
+# (source start file, target name, title, author,
+#  dir menu entry, description, category)
+texinfo_documents = [
+    (master_doc, 'exomiser', u'exomiser Documentation',
+     author, 'exomiser', 'One line description of project.',
+     'Miscellaneous'),
+]
+
+
+# -- Options for Epub output -------------------------------------------------
+
+# Bibliographic Dublin Core info.
+epub_title = project
+epub_author = author
+epub_publisher = author
+epub_copyright = copyright
+
+# The unique identifier of the text. This can be a ISBN number
+# or the project homepage.
+#
+# epub_identifier = ''
+
+# A unique identification for the text.
+#
+# epub_uid = ''
+
+# A list of files that should not be packed into the epub file.
+epub_exclude_files = ['search.html']
+
+
+# -- Extension configuration -------------------------------------------------

docs/index.rst

@@ -0,0 +1,20 @@
+.. exomiser documentation master file, created by
+   sphinx-quickstart on Wed Mar 07 09:59:52 2018.
+   You can adapt this file completely to your liking, but it should at least
+   contain the root `toctree` directive.
+
+Welcome to exomiser's documentation!
+====================================
+
+.. toctree::
+   :maxdepth: 2
+   :caption: Contents:
+
+
+
+Indices and tables
+==================
+
+* :ref:`genindex`
+* :ref:`modindex`
+* :ref:`search`

docs/make.bat

@@ -0,0 +1,36 @@
+@ECHO OFF
+
+pushd %~dp0
+
+REM Command file for Sphinx documentation
+
+if "%SPHINXBUILD%" == "" (
+	set SPHINXBUILD=sphinx-build
+)
+set SOURCEDIR=.
+set BUILDDIR=.build
+set SPHINXPROJ=exomiser
+
+if "%1" == "" goto help
+
+%SPHINXBUILD% >NUL 2>NUL
+if errorlevel 9009 (
+	echo.
+	echo.The 'sphinx-build' command was not found. Make sure you have Sphinx
+	echo.installed, then set the SPHINXBUILD environment variable to point
+	echo.to the full path of the 'sphinx-build' executable. Alternatively you
+	echo.may add the Sphinx directory to PATH.
+	echo.
+	echo.If you don't have Sphinx installed, grab it from
+	echo.http://sphinx-doc.org/
+	exit /b 1
+)
+
+%SPHINXBUILD% -M %1 %SOURCEDIR% %BUILDDIR% %SPHINXOPTS%
+goto end
+
+:help
+%SPHINXBUILD% -M help %SOURCEDIR% %BUILDDIR% %SPHINXOPTS%
+
+:end
+popd

exomiser-cli/.mvn/wrapper/maven-wrapper.properties

@@ -1 +1 @@
-distributionUrl=https://repo1.maven.org/maven2/org/apache/maven/apache-maven/3.5.0/apache-maven-3.5.0-bin.zip
+distributionUrl=https://repo1.maven.org/maven2/org/apache/maven/apache-maven/3.5.2/apache-maven-3.5.2-bin.zip

exomiser-cli/CHANGELOG.md

@@ -1,5 +1,26 @@
 # The Exomiser Command Line Executable - Changelog
 
+## 10.0.0 2018-03-07
+- Deprecated extended cli options as these were less capable than the analysis file. Options are now ```--analysis``` or ```--analysis-batch``` only. See the ```.yml``` files in the ```examples``` directory for recommended scripts.
+- Exomiser can now analyse samples against multiple inheritance modes in one run using the new ```inheritanceModes``` field. This also allows variants to be considered under a model with a maximum frequency (%) cut-off. See example ```.yml``` files for more details. 
+     ```yaml
+        inheritanceModes: {
+             AUTOSOMAL_DOMINANT: 0.1,
+             AUTOSOMAL_RECESSIVE_HOM_ALT: 0.1,
+             AUTOSOMAL_RECESSIVE_COMP_HET: 2.0,
+             X_DOMINANT: 0.1,
+             X_RECESSIVE_HOM_ALT: 0.1,
+             X_RECESSIVE_COMP_HET: 2.0,
+             MITOCHONDRIAL: 0.2
+        }
+     ```
+- The old ```modeOfInheritance``` option will still work, although it will only run with default frequency cut-offs and may be removed in a later release, so please update your analyses.
+- The new ```1802_phenotype``` data release will not work on older exomiser versions as the PPI data is now shipped in a much more efficient storage format. This reduces the startup time to zero and reduces the memory footprint by approx 1 GB. We *highly* recommend you update older releases to the latest version in order to benefit from more recent phenotype data.
+- Default variant scores for ```FRAMESHIFT```, ```NONSENSE```, ```SPLICING```, ```STOPLOSS``` and ```STARTLOSS``` have been increased from 0.95 to the maximum score of 1.0 to reflect clinical interpretation of these variant consequences.
+
+## 9.0.1 2018-01-15
+- Now able to analyse ```MITOCHONDRIAL``` inheritance mode.
+
 ## 9.0.0 2017-12-12
 - Exomiser can now analyse hg19 or hg38 samples - see ```application.properties``` for setup details.
 - Analysis file has new ```genomeAssembly:``` field - see example ```.yml``` files. Will default to hg19 if not specified.