Introduction

The Whole Genome Sequencing (WGS) Clinical Assay combines the DNA Alignment, WGS Quality Control, Germline SNVs and small Indels, and Single Sample SVs subworkflows into one WGS workflow. Please see each linked Wiki above for additional details regarding each subworkflow.

Tutorials

Command Line

Please see each subworkflow listed above for a command line tutorial that exemplifies each step that is run as part of the entire workflow.

Workflow Definitions

The Common Workflow Language (CWL) definitions for the entire workflow are contained in the Analysis Workflows GitHub repository. Specifically, the germline_wgs.cwl is the pipeline definition that will run the entire process including each subworkflow listed in the Introduction.

Steps

Inputs

Name	Description	Example	Subworkflow
bams			DNA Alignment
bqsr_intervals			DNA Alignment
dbsnp_vcf			DNA Alignment
known_indels			DNA Alignment
mills			DNA Alignment
readgroups			DNA Alignment
reference			DNA Alignment, WGS Quality Control, Germline SNVs and small Indels, Single Sample SVs
annotate_coding_only			Germline SNVs and small Indels
emit_reference_confidence		GVCF	Germline SNVs and small Indels
gvcf_gq_bands		NULL	Germline SNVs and small Indels
intervals		chr1 .. chr22, chrX, chrY	Germline SNVs and small Indels
synonyms_file			Germline SNVs and small Indels
variant_reporting_intervals			Germline SNVs and small Indels
vep_cache_dir	Location of a local ensembl cache to be used by vep		Germline SNVs and small Indels, Single Sample SVs
vep_ensembl_assembly	Which species assembly version vep should use	GRCh38	Germline SNVs and small Indels, Single Sample SVs
vep_ensembl_species	Which species vep should use	homo_sapiens	Germline SNVs and small Indels, Single Sample SVs
vep_ensembl_version	Which ensembl release vep should use	95	Germline SNVs and small Indels, Single Sample SVs
cnvkit_diagram	Create an ideogram of copy ratios on chromosomes as a pdf	FALSE	Single Sample SVs
cnvkit_drop_low_coverage	Helps avoid false positive deletions in low quality tumor samples	FALSE	Single Sample SVs
cnvkit_male_reference	Use/assume a male reference	FALSE	Single Sample SVs
cnvkit_method	Sequencing protocol used	wgs	Single Sample SVs
cnvkit_reference_cnn	A copy number reference file against which potential copy number variants will be evaluated		Single Sample SVs
cnvkit_scatter_plot	Create a whole genome copy ratio profile as a pdf scatter plot		Single Sample SVs
cnvkit_vcf_name	custom name to use for the cnvkit output vcf		Single Sample SVs
manta_call_regions			Single Sample SVs
manta_non_wgs			Single Sample SVs
manta_output_contigs			Single Sample SVs
maximum_sv_pop_freq			Single Sample SVs
merge_estimate_sv_distance		TRUE	Single Sample SVs
merge_max_distance		1000	Single Sample SVs
merge_min_sv_size		1	Single Sample SVs
merge_min_svs			Single Sample SVs
merge_same_strand		TRUE	Single Sample SVs
merge_same_type		TRUE	Single Sample SVs
merge_sv_pop_freq_db			Single Sample SVs
smoove_exclude_regions			Single Sample SVs
sv_filter_interval_lists			Single Sample SVs
sv_variants_to_table_fields		CHROM, POS, ID, REF, ALT, SVLEN, CHR2, END, POPFREQ_AF, POPFREQ_VarID, NSAMP	Single Sample SVs
sv_variants_to_table_genotype_fields		GT	Single Sample SVs
custom_clinvar_vcf			WGS Quality Control
custom_gnomad_vcf			WGS Quality Control
minimum_base_quality			WGS Quality Control
minimum_mapping_quality			WGS Quality Control
omni_vcf			WGS Quality Control
per_base_intervals			WGS Quality Control
per_target_intervals			WGS Quality Control
picard_metric_accumulation_level			WGS Quality Control
qc_intervals			WGS Quality Control
summary_intervals			WGS Quality Control

Outputs

Filename	Pipeline Step	Software	Description
annotated.coding_variant_filtered.vcf.gz
annotated.coding_variant_filtered.vcf.gz.tbi
annotated.max_sv_pf_filtered.vcf
annotated.vcf.gz
annotated.vcf.gz.tbi
annotated.vcf_summary.html
candidateSmallIndels.vcf.gz
candidateSmallIndels.vcf.gz.tbi
candidateSV.vcf.gz
candidateSV.vcf.gz.tbi
chr##.g.vcf.gz
chr##.g.vcf.gz.tbi
final.AlignmentSummaryMetrics.txt
final.antitargetcoverage.cnn
final.bam.bigwig
final.bam.flagstat
final.bam.merged.NameSorted.mark_dups_metrics.txt
final.base-clinvar-HsMetrics.txt
final.base-clinvar-PerBaseCoverage.txt
final.cnr
final.cns
final.cnvkit.vcf
final.crai
final.cram
final.cram.crai
final.InsertSizeHistogram.pdf
final.InsertSizeMetrics.txt
final.target-acmg_genes-HsMetrics.txt
final.target-acmg_genes-PerTargetCoverage.txt
final.targetcoverage.cnn
final.target-gencode_exons-HsMetrics.txt
final.target-gencode_exons-PerTargetCoverage.txt
final.target-gencode_genes-HsMetrics.txt
final.target-gencode_genes-PerTargetCoverage.txt
final.VerifyBamId.depthSM
final.VerifyBamId.selfSM
GcBiasMetricsChart.pdf
GcBiasMetricsSummary.txt
GcBiasMetrics.txt	Alignment and QC	CollectGcBiasMetrics (Picard)	See https://broadinstitute.github.io/picard/picard-metric-definitions.html#GcBiasMetrics
intersect-acmg_genes.vcf.gz
intersect-acmg_genes.vcf.gz.tbi
intersect-gencode_exons.vcf.gz
intersect-gencode_exons.vcf.gz.tbi
intersect-gencode_genes.vcf.gz
intersect-gencode_genes.vcf.gz.tbi
select_variants.vcf.gz
select_variants.vcf.gz.tbi
sorted.vcf
SV-smoove.genotyped.vcf.gz
SV-smoove.genotyped.vcf.gz.csi
tumorSV.vcf.gz
tumorSV.vcf.gz.tbi
variants.annotated.tsv
WgsMetrics.txt