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Snakefile
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# Main Snakefile for the varfish-db-downloader.
#
# This Snakemake workflow allows for downlaoding the background data needed by VarFish. The data
# is downloaded from public sources and transformed as needed. Eventually, the data is converted
# into RocksDB databases or protobuf binary files that can be used directly by
# ``varfish-server-worker`` and is used in the backend for filtering and/or exposed to the
# user via a REST API.
from varfish_db_downloader.versions import (
DATA_VERSIONS as DV,
PACKAGE_VERSIONS as PV,
FORCE_TODAY,
TODAY,
RUNS_IN_CI,
)
# The prefix to use for all shell commands.
SHELL_PREFIX = "export LC_ALL=C; set -x -euo pipefail;"
# Setup the shell prefix by default.
shell.prefix(SHELL_PREFIX)
# Regular expression for genome release.
RE_GENOME = r"grch(37|38)"
# Regular expression for a "word".
RE_NAME = r"[\w-]+"
# Regular expression for versions.
RE_VERSION = r"\w+(\.\w+)*"
# Regular expression for versions.
RE_VERSION_MULTI = r"\w+(\.\w+)*(\+\w+(\.\w+)*)*"
# Gene symbols for the "dev" subset.
DEV_GENE_SYMBOLS = "|".join(
[
"BRCA1", # commonly tested, well-annotated
"TTN", # commonly tested, well-annotated
"OMA1", # commonly tested, well-annotated
"SAMD11", # very small coordinates => found when CI=true
]
)
# Padding to add to exons in dev and exons mode.
EXON_PADDING = 200
# ===============================================================================================
# Test Mode
# ===============================================================================================
# Activate test mode by prepending the path to the "test-mode-bin" directory to the PATH.
if RUNS_IN_CI:
cwd = os.getcwd()
old_path = os.environ["PATH"]
os.environ["PATH"] = f"{cwd}/test-mode-bin:{old_path}"
# ===============================================================================================
# Top-Level Rules
# ===============================================================================================
## help -- print this help
rule help:
input:
"Snakefile",
run:
shell.prefix("") # no ``set -x`` for this rule
shell(
r"""
echo
echo "=== Available Rules ==="
echo
for f in Snakefile $(find rules/* -name '*.smk' | sort); do
echo "--- $f ---"
echo
grep '^##' $f
echo
grep -e '^rule' $f
echo
done
"""
)
## all -- run all rules
rule all:
input:
# == work directory =====================================================================
#
# genes
f"work/download/genes/rcnv/2022/Collins_rCNV_2022.dosage_sensitivity_scores.tsv.gz",
"work/download/genes/alphamissense/1/AlphaMissense_gene_hg38.tsv.gz",
f"work/download/genes/ctd/{DV.today}/CTD_diseases.tsv.gz",
f"work/download/do/{DV.today}/omim-unmapped.csv",
f"work/genes/dbnsfp/{DV.dbnsfp}/genes.tsv.gz",
"work/genes/decipher/v3/decipher_hi_prediction.tsv",
f"work/genes/ensembl/{DV.ensembl}/ensembl_xlink.tsv",
f"work/genes/enst_ensg/grch37/{DV.ensembl_37}/enst_ensg.tsv",
f"work/genes/entrez/{DV.today}/gene_info.jsonl",
f"work/genes/gnomad/{DV.gnomad_constraints}/gnomad_constraints.tsv",
f"work/genes/hgnc/{DV.today}/hgnc_info.jsonl",
f"work/genes/omim/{DV.hpo}+{DV.today}/omim_diseases.tsv",
f"work/genes/orphadata/{DV.orphadata}/orphadata.jsonl",
f"work/genes/mondo/{DV.today}/mondo.obo",
"work/genes/rcnv/2022/rcnv_collins_2022.tsv",
"work/genes/shet/2019/shet_weghorn_2019.tsv",
f"work/genes/clingen/{DV.today}/ClinGen_gene_curation_list_GRCh37.tsv",
f"work/genes/clingen/{DV.today}/ClinGen_gene_curation_list_GRCh38.tsv",
"work/genes/domino/20190219/domino.tsv",
# reference-specific annotations
# -- background/population sequence variants and annotations thereof
# ---- GRCh37
f"work/download/annos/grch37/seqvars/cadd/{DV.cadd}/whole_genome_SNVs_inclAnno.tsv.gz",
f"work/download/annos/grch37/seqvars/cadd/{DV.cadd}/InDels_inclAnno.tsv.gz",
f"work/download/annos/grch37/seqvars/dbnsfp/{DV.dbnsfp}a/LICENSE.txt",
f"work/download/annos/grch37/seqvars/dbnsfp/{DV.dbnsfp}c/LICENSE.txt",
f"work/download/annos/grch37/seqvars/dbscsnv/{DV.dbscsnv}/dbscSNV{DV.dbscsnv}.chr1",
f"work/download/annos/grch37/seqvars/dbsnp/{DV.dbsnp}/dbsnp.vcf.gz",
f"work/annos/grch37/seqvars/helixmtdb/{DV.helixmtdb}/helixmtdb.vcf.gz",
f"work/annos/grch37/seqvars/gnomad_mtdna/{DV.gnomad_mtdna}/gnomad_mtdna.vcf.gz",
f"work/download/annos/grch37/seqvars/gnomad_exomes/{DV.gnomad_v2}/.done",
f"work/download/annos/grch37/seqvars/gnomad_genomes/{DV.gnomad_v2}/.done",
# ---- GRCh38
f"work/download/annos/grch38/seqvars/cadd/{DV.cadd}/whole_genome_SNVs_inclAnno.tsv.gz",
f"work/download/annos/grch38/seqvars/cadd/{DV.cadd}/gnomad.genomes.r3.0.indel_inclAnno.tsv.gz",
# NB: dbNSFP is dual reference (for download)
# NB: dbscSNV is dual reference (for download)
f"work/download/annos/grch37/seqvars/dbsnp/{DV.dbsnp}/dbsnp.vcf.gz",
f"work/annos/grch38/seqvars/helixmtdb/{DV.helixmtdb}/helixmtdb.vcf.gz",
f"work/annos/grch38/seqvars/gnomad_mtdna/{DV.gnomad_mtdna}/gnomad_mtdna.vcf.gz",
f"work/download/annos/grch38/seqvars/gnomad_exomes/{DV.gnomad_v4}/.done",
f"work/download/annos/grch38/seqvars/gnomad_genomes/{DV.gnomad_v4}/.done",
# -- genome browser "features" (position-specific)
# ---- GRCh37
f"work/annos/grch37/features/cons/{DV.ucsc_cons_37}/ucsc_conservation.tsv",
f"work/annos/grch37/features/ensembl/{DV.ensembl_37}/ensembl_genes.bed.gz",
f"work/annos/grch37/features/refseq/{DV.refseq_37}/refseq_genes.bed.gz",
# ---- GRCh38
f"work/annos/grch38/features/cons/{DV.ucsc_cons_38}/ucsc_conservation.tsv",
f"work/annos/grch38/features/ensembl/{DV.ensembl_38}/ensembl_genes.bed.gz",
f"work/annos/grch38/features/refseq/{DV.refseq_38}/refseq_genes.bed.gz",
#
# == output directory ===================================================================
#
# -- mehari data
# ---- frequencies (via annonars)
f"output/full/mehari/freqs-grch37-{DV.gnomad_v2}+{DV.gnomad_v2}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/mehari/freqs-grch38-{DV.gnomad_v4}+{DV.gnomad_v4}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
# -- annonars data
# ----- sequence variant annotations
f"output/full/annonars/alphamissense-grch37-{DV.alphamissense}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/alphamissense-grch38-{DV.alphamissense}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/cadd-grch37-{DV.cadd}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/cadd-grch38-{DV.cadd}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbsnp-grch37-{DV.dbsnp}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbsnp-grch38-{DV.dbsnp}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbnsfp-grch37-{DV.dbnsfp}a+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbnsfp-grch38-{DV.dbnsfp}a+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbnsfp-grch37-{DV.dbnsfp}c+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbnsfp-grch38-{DV.dbnsfp}c+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbscsnv-grch37-{DV.dbscsnv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/dbscsnv-grch38-{DV.dbscsnv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-mtdna-grch37-{DV.gnomad_mtdna}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-mtdna-grch38-{DV.gnomad_mtdna}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-exomes-grch37-{DV.gnomad_v2}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-exomes-grch38-{DV.gnomad_v4}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-genomes-grch37-{DV.gnomad_v2}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-genomes-grch38-{DV.gnomad_v4}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/helixmtdb-grch37-{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/helixmtdb-grch38-{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-sv-exomes-grch37-{DV.exac_cnv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-sv-exomes-grch38-{DV.gnomad_cnv4}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-sv-genomes-grch37-{DV.gnomad_sv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/gnomad-sv-genomes-grch38-{DV.gnomad_sv4}+{PV.annonars}/rocksdb/IDENTITY",
# ----- sequence annotation
f"output/full/annonars/functional-grch37-{DV.refseq_fe_37}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/functional-grch38-{DV.refseq_fe_38}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/regions-grch37-{DV.today}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/regions-grch38-{DV.today}+{PV.annonars}/rocksdb/IDENTITY",
# ----- conservation
f"output/full/annonars/cons-grch37-{DV.ucsc_cons_37}+{PV.annonars}/rocksdb/IDENTITY",
f"output/full/annonars/cons-grch38-{DV.ucsc_cons_38}+{PV.annonars}/rocksdb/IDENTITY",
# ----- genes
f"output/full/annonars/genes-{DV.acmg_sf}+{DV.gnomad_constraints}+{DV.dbnsfp}+{DV.hpo}+{DV.today}+{PV.annonars}/rocksdb/IDENTITY",
# -- worker data
f"output/full/worker/genes-xlink-{DV.today}+{PV.worker}/genes-xlink.bin",
f"output/full/worker/acmg-sf-{DV.acmg_sf}+{PV.worker}/acmg_sf.tsv",
f"output/full/worker/mim2gene-{DV.today}+{PV.worker}/mim2gene.tsv",
f"output/full/worker/masked-repeat-grch37-{DV.ucsc_rmsk_37}+{PV.worker}/masked-repeat.bin",
f"output/full/worker/masked-repeat-grch38-{DV.ucsc_rmsk_38}+{PV.worker}/masked-repeat.bin",
f"output/full/worker/masked-segdup-grch37-{DV.ucsc_genomic_super_dups_37}+{PV.worker}/masked-segdup.bin",
f"output/full/worker/masked-segdup-grch38-{DV.ucsc_genomic_super_dups_38}+{PV.worker}/masked-segdup.bin",
f"output/full/worker/bgdb-dbvar-grch37-{DV.dbvar}+{PV.worker}/bgdb-dbvar.bin",
f"output/full/worker/bgdb-dbvar-grch38-{DV.dbvar}+{PV.worker}/bgdb-dbvar.bin",
f"output/full/worker/bgdb-dgv-grch37-{DV.dgv}+{PV.worker}/bgdb-dgv.bin",
f"output/full/worker/bgdb-dgv-grch38-{DV.dgv}+{PV.worker}/bgdb-dgv.bin",
f"output/full/worker/bgdb-dgv-gs-grch37-{DV.dgv}+{PV.worker}/bgdb-dgv-gs.bin",
f"output/full/worker/bgdb-dgv-gs-grch38-{DV.dgv}+{PV.worker}/bgdb-dgv-gs.bin",
f"output/full/worker/bgdb-gnomad-grch37-{DV.gnomad_sv}+{PV.worker}/bgdb-gnomad.bin",
f"output/full/worker/bgdb-exac-grch37-{DV.exac_cnv}+{PV.worker}/bgdb-exac.bin",
f"output/full/worker/bgdb-gnomad-exomes-cnv-grch38-{DV.gnomad_sv4}+{PV.worker}/bgdb-gnomad-exomes-cnv-grch38.bin",
f"output/full/worker/bgdb-gnomad-genomes-sv-grch38-{DV.gnomad_sv4}+{PV.worker}/bgdb-gnomad-genomes-sv-grch38.bin",
f"output/full/worker/bgdb-g1k-grch37-{DV.g1k_svs}+{PV.worker}/bgdb-g1k.bin",
f"output/full/worker/clinvar-strucvars-grch37-{DV.clinvar_version}+{PV.worker}/clinvar-strucvars.bin",
f"output/full/worker/clinvar-strucvars-grch38-{DV.clinvar_version}+{PV.worker}/clinvar-strucvars.bin",
f"output/full/worker/patho-mms-grch37-{DV.patho_mms}+{PV.worker}/patho-mms.bed",
f"output/full/worker/patho-mms-grch38-{DV.patho_mms}+{PV.worker}/patho-mms.bed",
"output/full/worker/tads-grch37-dixon2015/hesc.bed",
"output/full/worker/tads-grch38-dixon2015/hesc.bed",
# -- mehari data
f"output/full/mehari/genes-xlink-{DV.today}/genes-xlink.tsv",
f"output/full/mehari/genes-txs-grch37-{DV.mehari_tx}/mehari-data-txs-grch37-{DV.mehari_tx}.bin.zst",
f"output/full/mehari/genes-txs-grch38-{DV.mehari_tx}/mehari-data-txs-grch38-{DV.mehari_tx}.bin.zst",
# ----- HPO
f"output/full/viguno/hpo-{DV.hpo}+{PV.viguno}/hp.obo",
f"output/full/viguno/hpo-{DV.hpo}+{PV.viguno}/phenotype.hpoa",
f"output/full/viguno/hpo-{DV.hpo}+{PV.viguno}/phenotype_to_genes.txt",
f"output/full/viguno/hpo-{DV.hpo}+{PV.viguno}/hpo.bin",
# ----- background/population structural variants and annotations thereof
f"output/full/tracks/track-strucvars-dbvar-grch37-{DV.dbvar}+{DV.tracks}/dbvar.bed.gz",
f"output/full/tracks/track-strucvars-dbvar-grch38-{DV.dbvar}+{DV.tracks}/dbvar.bed.gz",
f"output/full/tracks/track-strucvars-dgv-grch37-{DV.dgv}+{DV.tracks}/dgv.bed.gz",
f"output/full/tracks/track-strucvars-dgv-grch38-{DV.dgv}+{DV.tracks}/dgv.bed.gz",
f"output/full/tracks/track-strucvars-dgv-gs-grch37-{DV.dgv_gs}+{DV.tracks}/dgv-gs.bed.gz",
f"output/full/tracks/track-strucvars-dgv-gs-grch38-{DV.dgv_gs}+{DV.tracks}/dgv-gs.bed.gz",
f"output/full/tracks/track-strucvars-exac-grch37-{DV.exac_cnv}+{DV.tracks}/exac.bed.gz",
f"output/full/tracks/track-strucvars-g1k-grch37-{DV.g1k_svs}+{DV.tracks}/g1k.bed.gz",
f"output/full/tracks/track-strucvars-gnomad-grch37-{DV.gnomad_sv}+{DV.tracks}/gnomad.bed.gz",
f"output/full/tracks/track-strucvars-gnomad-sv-grch38-{DV.gnomad_sv4}+{DV.tracks}/gnomad-sv.bed.gz",
f"output/full/tracks/track-strucvars-gnomad-cnv-grch38-{DV.gnomad_cnv4}+{DV.tracks}/gnomad-cnv.bed.gz",
# ----- known pathogenic MMS
f"output/full/tracks/track-strucvars-patho-mms-grch37-{DV.patho_mms}+{DV.tracks}/patho-mms.bed",
f"output/full/tracks/track-strucvars-patho-mms-grch38-{DV.patho_mms}+{DV.tracks}/patho-mms.bed",
# ----- problematic regions (rmsk, genomicSuperDups, altSeqLiftOverPsl, fixSeqLiftOverPsl)
f"output/full/tracks/track-features-ucsc-genomicsuperdups-grch37-{DV.ucsc_genomic_super_dups_37}+{DV.tracks}/genomicSuperDups.bed.gz",
f"output/full/tracks/track-features-ucsc-genomicsuperdups-grch38-{DV.ucsc_genomic_super_dups_38}+{DV.tracks}/genomicSuperDups.bed.gz",
f"output/full/tracks/track-features-ucsc-rmsk-grch37-{DV.ucsc_rmsk_37}+{DV.tracks}/rmsk.bed.gz",
f"output/full/tracks/track-features-ucsc-rmsk-grch38-{DV.ucsc_rmsk_38}+{DV.tracks}/rmsk.bed.gz",
f"output/full/tracks/track-features-ucsc-altseqliftoverpsl-grch37-{DV.ucsc_alt_seq_liftover_37}+{DV.tracks}/altSeqLiftOverPsl.bed.gz",
f"output/full/tracks/track-features-ucsc-altseqliftoverpsl-grch38-{DV.ucsc_alt_seq_liftover_38}+{DV.tracks}/altSeqLiftOverPsl.bed.gz",
f"output/full/tracks/track-features-ucsc-fixseqliftoverpsl-grch37-{DV.ucsc_fix_seq_liftover_37}+{DV.tracks}/fixSeqLiftOverPsl.bed.gz",
f"output/full/tracks/track-features-ucsc-fixseqliftoverpsl-grch38-{DV.ucsc_fix_seq_liftover_38}+{DV.tracks}/fixSeqLiftOverPsl.bed.gz",
# ----- tads
f"output/full/tracks/track-tads-grch37-dixon2015+{DV.tracks}/hesc.bed",
f"output/full/tracks/track-tads-grch38-dixon2015+{DV.tracks}/hesc.bed",
# ----- probesets
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v4-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v4-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v5-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v5-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v6-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v6-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v7-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v7-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v8-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/agilent-all-exon-v8-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/idt-xgen-exome-research-panel-v1-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/idt-xgen-exome-research-panel-v1-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/idt-xgen-exome-research-panel-v2-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/idt-xgen-exome-research-panel-v2-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-comprehensive-exome-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-comprehensive-exome-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-core-exome-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-core-exome-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-exome-v2_0-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-exome-v2_0-grch38-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-refseq-exome-grch37-{DV.tracks}.bed.gz",
f"output/full/tracks/track-enrichment-probesets-targets/twist-refseq-exome-grch38-{DV.tracks}.bed.gz",
#
# == development (reduced data) directories =============================================
#
# -- targets
f"output/reduced-dev/targets/grch37/refseq/{DV.refseq_37}/refseq_target_exons.bed.gz",
f"output/reduced-dev/targets/grch38/refseq/{DV.refseq_38}/refseq_target_exons.bed.gz",
# -- viguno
f"output/reduced-dev/viguno/hpo-{DV.hpo}+{PV.viguno}/hp.obo",
f"output/reduced-dev/viguno/hpo-{DV.hpo}+{PV.viguno}/phenotype.hpoa",
f"output/reduced-dev/viguno/hpo-{DV.hpo}+{PV.viguno}/phenotype_to_genes.txt",
f"output/reduced-dev/viguno/hpo-{DV.hpo}+{PV.viguno}/hpo.bin",
# -- annonars
f"output/reduced-dev/annonars/cadd-grch37-{DV.cadd}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/cadd-grch37-{DV.cadd}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/cadd-grch38-{DV.cadd}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/cadd-grch38-{DV.cadd}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/cons-grch37-{DV.ucsc_cons_37}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/cons-grch37-{DV.ucsc_cons_37}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/cons-grch38-{DV.ucsc_cons_38}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/cons-grch38-{DV.ucsc_cons_38}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbnsfp-grch37-{DV.dbnsfp}a+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbnsfp-grch37-{DV.dbnsfp}a+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbnsfp-grch37-{DV.dbnsfp}c+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbnsfp-grch37-{DV.dbnsfp}c+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbnsfp-grch38-{DV.dbnsfp}a+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbnsfp-grch38-{DV.dbnsfp}a+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbnsfp-grch38-{DV.dbnsfp}c+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbnsfp-grch38-{DV.dbnsfp}c+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbscsnv-grch37-{DV.dbscsnv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbscsnv-grch37-{DV.dbscsnv}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbscsnv-grch38-{DV.dbscsnv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbscsnv-grch38-{DV.dbscsnv}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbsnp-grch37-{DV.dbsnp}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbsnp-grch37-{DV.dbsnp}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/dbsnp-grch38-{DV.dbsnp}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/dbsnp-grch38-{DV.dbsnp}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/gnomad-exomes-grch37-{DV.gnomad_v2}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/gnomad-exomes-grch37-{DV.gnomad_v2}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/gnomad-exomes-grch38-{DV.gnomad_v4}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/gnomad-exomes-grch38-{DV.gnomad_v4}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/gnomad-genomes-grch37-{DV.gnomad_v2}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/gnomad-genomes-grch37-{DV.gnomad_v2}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/annonars/gnomad-genomes-grch38-{DV.gnomad_v4}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/annonars/gnomad-genomes-grch38-{DV.gnomad_v4}+{PV.annonars}/spec.yaml",
# -- mehari
f"output/reduced-dev/mehari/freqs-grch37-{DV.gnomad_v2}+{DV.gnomad_v2}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/mehari/freqs-grch37-{DV.gnomad_v2}+{DV.gnomad_v2}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/spec.yaml",
f"output/reduced-dev/mehari/freqs-grch38-{DV.gnomad_v4}+{DV.gnomad_v4}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-dev/mehari/freqs-grch38-{DV.gnomad_v4}+{DV.gnomad_v4}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/spec.yaml",
#
# == exomes (reduced data) directories ==================================================
#
# -- targets
f"output/reduced-exomes/targets/grch37/refseq/{DV.refseq_37}/refseq_target_exons.bed.gz",
f"output/reduced-exomes/targets/grch38/refseq/{DV.refseq_38}/refseq_target_exons.bed.gz",
# -- viguno
f"output/reduced-exomes/viguno/hpo-{DV.hpo}+{PV.viguno}/hp.obo",
f"output/reduced-exomes/viguno/hpo-{DV.hpo}+{PV.viguno}/phenotype.hpoa",
f"output/reduced-exomes/viguno/hpo-{DV.hpo}+{PV.viguno}/phenotype_to_genes.txt",
f"output/reduced-exomes/viguno/hpo-{DV.hpo}+{PV.viguno}/hpo.bin",
# -- annonars
f"output/reduced-exomes/annonars/cadd-grch37-{DV.cadd}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/cadd-grch37-{DV.cadd}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/cadd-grch38-{DV.cadd}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/cadd-grch38-{DV.cadd}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/cons-grch37-{DV.ucsc_cons_37}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/cons-grch37-{DV.ucsc_cons_37}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/cons-grch38-{DV.ucsc_cons_38}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/cons-grch38-{DV.ucsc_cons_38}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbnsfp-grch37-{DV.dbnsfp}a+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbnsfp-grch37-{DV.dbnsfp}a+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbnsfp-grch37-{DV.dbnsfp}c+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbnsfp-grch37-{DV.dbnsfp}c+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbnsfp-grch38-{DV.dbnsfp}a+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbnsfp-grch38-{DV.dbnsfp}a+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbnsfp-grch38-{DV.dbnsfp}c+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbnsfp-grch38-{DV.dbnsfp}c+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbscsnv-grch37-{DV.dbscsnv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbscsnv-grch37-{DV.dbscsnv}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbscsnv-grch38-{DV.dbscsnv}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbscsnv-grch38-{DV.dbscsnv}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbsnp-grch37-{DV.dbsnp}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbsnp-grch37-{DV.dbsnp}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/dbsnp-grch38-{DV.dbsnp}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/dbsnp-grch38-{DV.dbsnp}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/gnomad-exomes-grch37-{DV.gnomad_v2}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/gnomad-exomes-grch37-{DV.gnomad_v2}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/gnomad-exomes-grch38-{DV.gnomad_v4}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/gnomad-exomes-grch38-{DV.gnomad_v4}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/gnomad-genomes-grch37-{DV.gnomad_v2}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/gnomad-genomes-grch37-{DV.gnomad_v2}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/annonars/gnomad-genomes-grch38-{DV.gnomad_v4}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/annonars/gnomad-genomes-grch38-{DV.gnomad_v4}+{PV.annonars}/spec.yaml",
# -- mehari
f"output/reduced-exomes/mehari/freqs-grch37-{DV.gnomad_v2}+{DV.gnomad_v2}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/mehari/freqs-grch37-{DV.gnomad_v2}+{DV.gnomad_v2}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/spec.yaml",
f"output/reduced-exomes/mehari/freqs-grch38-{DV.gnomad_v4}+{DV.gnomad_v4}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/rocksdb/IDENTITY",
f"output/reduced-exomes/mehari/freqs-grch38-{DV.gnomad_v4}+{DV.gnomad_v4}+{DV.gnomad_mtdna}+{DV.helixmtdb}+{PV.annonars}/spec.yaml",
# ===============================================================================================
# Modular Snakefile Includes
# ===============================================================================================
# -- work directory -----------------------------------------------------------------------------
# Misc rules.
include: "rules/work/misc/hpo.smk"
# Gene-related rules.
include: "rules/work/genes/alphamissense.smk"
include: "rules/work/genes/dbnsfp.smk"
include: "rules/work/genes/clingen.smk"
include: "rules/work/genes/conditions.smk"
include: "rules/work/genes/ctd.smk"
include: "rules/work/genes/do.smk"
include: "rules/work/genes/decipher.smk"
include: "rules/work/genes/ensembl.smk"
include: "rules/work/genes/gnomad.smk"
include: "rules/work/genes/gtex.smk"
include: "rules/work/genes/hgnc.smk"
include: "rules/work/genes/mehari_data_tx.smk"
include: "rules/work/genes/ncbi.smk"
include: "rules/work/genes/omim.smk"
include: "rules/work/genes/panelapp.smk"
include: "rules/work/genes/mondo.smk"
include: "rules/work/genes/orphadata.smk"
include: "rules/work/genes/rcnv.smk"
include: "rules/work/genes/shet.smk"
include: "rules/work/genes/domino.smk"
# Reference sequence--related rules.
include: "rules/work/reference/human.smk"
# Features (position and not variant specific).
include: "rules/work/annos/features/cons.smk"
include: "rules/work/annos/features/ensembl.smk"
include: "rules/work/annos/features/refseq.smk"
include: "rules/work/annos/features/tads.smk"
include: "rules/work/annos/features/ucsc.smk"
# Sequence variants and annotations.
include: "rules/work/annos/seqvars/alphamissense.smk"
include: "rules/work/annos/seqvars/cadd.smk"
include: "rules/work/annos/seqvars/dbnsfp.smk"
include: "rules/work/annos/seqvars/dbscsnv.smk"
include: "rules/work/annos/seqvars/dbsnp.smk"
include: "rules/work/annos/seqvars/gnomad_mtdna.smk"
include: "rules/work/annos/seqvars/gnomad_nuclear.smk"
include: "rules/work/annos/seqvars/helix.smk"
# Structural variant related.
include: "rules/work/annos/strucvars/dbvar.smk"
include: "rules/work/annos/strucvars/dgv.smk"
include: "rules/work/annos/strucvars/exac.smk"
include: "rules/work/annos/strucvars/g1k.smk"
include: "rules/work/annos/strucvars/gnomad.smk"
include: "rules/work/annos/strucvars/clinvar.smk"
include: "rules/work/annos/strucvars/gnomad_sv4.smk"
# -- output directory ---------------------------------------------------------------------------
# ---- mehari
include: "rules/output/mehari/freqs.smk"
# ---- viguno
include: "rules/output/viguno/hpo.smk"
# ---- annonars
include: "rules/output/annonars/alphamissense.smk"
include: "rules/output/annonars/cadd.smk"
include: "rules/output/annonars/cons.smk"
include: "rules/output/annonars/dbnsfp.smk"
include: "rules/output/annonars/dbscsnv.smk"
include: "rules/output/annonars/dbsnp.smk"
include: "rules/output/annonars/gnomad_exomes.smk"
include: "rules/output/annonars/gnomad_genomes.smk"
include: "rules/output/annonars/gnomad_mtdna.smk"
include: "rules/output/annonars/gnomad_sv.smk"
include: "rules/output/annonars/helix.smk"
include: "rules/output/annonars/genes.smk"
include: "rules/output/annonars/functional.smk"
include: "rules/output/annonars/regions.smk"
# ---- worker
include: "rules/output/worker/patho_mms.smk"
include: "rules/output/worker/clinvar.smk"
include: "rules/output/worker/hgnc.smk"
include: "rules/output/worker/acmg.smk"
include: "rules/output/worker/mim2gene.smk"
include: "rules/output/worker/masked.smk"
include: "rules/output/worker/bgdb.smk"
include: "rules/output/worker/tads.smk"
# ---- tracks
include: "rules/output/tracks/exome_probesets.smk"
# -- reduced output directory (dev/exomes) ------------------------------------------------------
# ---- bed file
include: "rules/reduced/annonars.smk"
include: "rules/reduced/hpo.smk"
include: "rules/reduced/targets.smk"
include: "rules/reduced/mehari.smk"