hrDetect

Homologous Recombination Deficiency (HRD) Prediction Workflow using sig.tools

Overview

Dependencies

• tabix 1.9
• bcftools 1.9
• sigtools 0.0.0.9000

Usage

Cromwell

java -jar cromwell.jar run hrDetect.wdl --inputs inputs.json

Inputs

Required workflow parameters:

Parameter	Value	Description
outputFileNamePrefix	String	Name of sample matching the tumor sample in .vcf
structuralVcfFile	File	Input VCF file of structural variants (eg. from delly)
smallsVcfFile	File	Input VCF file of SNV and indels (small mutations) (eg. from mutect2)
smallsVcfIndex	File	Index file for smallsVcfFile
segFile	File	File for segmentations, used to estimate number of segments in Loss of heterozygosity (LOH) (eg. from sequenza)
reference	String	Reference genome version

Optional workflow parameters:

Parameter	Value	Default	Description

Optional task parameters:

Parameter	Value	Default	Description
filterStructural.modules	String	"bcftools/1.9"	Required environment modules
filterStructural.structuralQUALfilter	String	"PASS"	filter for filter calls to keep, eg. PASS
filterStructural.jobMemory	Int	5	Memory allocated for this job (GB)
filterStructural.threads	Int	1	Requested CPU threads
filterStructural.timeout	Int	1	Hours before task timeout
filterINDELs.VAF	Float	0.01	minimum variant allele frequency to retain variant
filterINDELs.QUALfilter	String	"FILTER~'haplotype'	FILTER~'clustered_events'
filterINDELs.jobMemory	Int	10	Memory allocated for this job (GB)
filterINDELs.threads	Int	1	Requested CPU threads
filterINDELs.timeout	Int	2	Hours before task timeout
filterSNVs.VAF	Float	0.01	minimum variant allele frequency to retain variant
filterSNVs.QUALfilter	String	"FILTER~'haplotype'	FILTER~'clustered_events'
filterSNVs.jobMemory	Int	10	Memory allocated for this job (GB)
filterSNVs.threads	Int	1	Requested CPU threads
filterSNVs.timeout	Int	2	Hours before task timeout
hrdResults.modules	String	"sigtools/2.4.1 sigtools-data/1.0 hrdetect-rscript/1.5.8"	Required environment modules
hrdResults.sigtoolrScript	String	"$HRDETECT_RSCRIPT_ROOT/scripts/sigTools_runthrough.R"	.R script containing sigtools
hrdResults.SVrefSigs	String	"$SIGTOOLS_DATA_ROOT/RefSigv0_Rearr.tsv"	reference signatures for SVs
hrdResults.SNVrefSigs	String	"$SIGTOOLS_DATA_ROOT/COSMIC_v1_SBS_GRCh38.txt"	reference signatures for SNVs
hrdResults.sigtoolsBootstrap	Int	200	Number of bootstraps for sigtools
hrdResults.indelCutoff	Int	50	minimum number of indels to run analysis
hrdResults.jobMemory	Int	50	Memory allocated for this job (GB)
hrdResults.threads	Int	1	Requested CPU threads
hrdResults.timeout	Int	15	Hours before task timeout

Outputs

Output	Type	Description	Labels
hrd_signatures	File	JSON file of hrdetect signatures	vidarr_label: hrd_signatures
SBS_exposures	File	JSON of structural variant signatures	vidarr_label: SBS_exposures
SV_exposures	File	JSON cataloguing structural variants	vidarr_label: SV_exposures
ID_catalog	File	JSON cataloguing indels	vidarr_label: ID_catalog

This section lists command(s) run by hrDetect workflow

• Running hrDetect

Generate list of PASS calls

	set -euo pipefail


	$BCFTOOLS_ROOT/bin/bcftools view -f '~{structuralQUALfilter}' ~{structuralVcfFile} >> ~{outputFileNamePrefix}.structural.PASS.vcf

	awk '$1 !~ "#" {print}' ~{structuralVcfFile} | wc -l >~{outputFileNamePrefix}.structural.filteringReport.txt
	awk '$1 !~ "#" {print}' ~{outputFileNamePrefix}.structural.PASS.vcf | wc -l >>~{outputFileNamePrefix}.structural.filteringReport.txt

Normalize and Filter calls

	set -euo pipefail

	$BCFTOOLS_ROOT/bin/bcftools norm --multiallelics - --fasta-ref ~{genome} ~{difficultRegions} ~{smallsVcfFile} | \
	$BCFTOOLS_ROOT/bin/bcftools filter -i "TYPE='~{smallType}'" | \
	$BCFTOOLS_ROOT/bin/bcftools filter -e "~{QUALfilter}" | \
	$BCFTOOLS_ROOT/bin/bcftools filter -i "(FORMAT/AD[0:1])/(FORMAT/AD[0:0]+FORMAT/AD[0:1]) >= ~{VAF}" >~{outputFileNamePrefix}.~{smallType}.VAF.vcf

	bgzip ~{outputFileNamePrefix}.~{smallType}.VAF.vcf
	tabix -p vcf ~{outputFileNamePrefix}.~{smallType}.VAF.vcf.gz

	zcat ~{smallsVcfFile} | awk '$1 !~ "#" {print}'  | wc -l >~{outputFileNamePrefix}.~{smallType}.filteringReport.txt
	zcat ~{outputFileNamePrefix}.~{smallType}.VAF.vcf.gz | awk '$1 !~ "#" {print}'  | wc -l >>~{outputFileNamePrefix}.~{smallType}.filteringReport.txt
  

Generate report

	set -euo pipefail

	Rscript ~{sigtoolrScript} \
		--sampleName ~{outputFileNamePrefix} \
		--snvFile ~{snvVcfFiltered} \
		--indelFile  ~{indelVcfFiltered} \
		--SVFile ~{SV_vcf_location} \
		--LOHFile ~{lohSegFile} \
		--bootstraps ~{sigtoolsBootstrap} \
		--genomeVersion ~{genomeVersion} \
		--indelCutoff ~{indelCutoff} \
		--SVrefSigs ~{SVrefSigs} \
		--SNVrefSigs ~{SNVrefSigs}

Support

For support, please file an issue on the Github project or send an email to [email protected] .

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