Skip to content

Add filtermutectcalls to filter mtdna variant calls #820

New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

Sign up for GitHub

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

Open
MatthieuBeukers wants to merge 3 commits into
base: main
Choose a base branch
from
Open

Add filtermutectcalls to filter mtdna variant calls #820

Show file tree
Hide file tree
Changes from all commits
Commits
Show all changes
3 commits
Select commit Hold shift + click to select a range
682acb4
Add filtermutectcalls to filter mtdna variant calls
MatthieuBeukers Apr 10, 2026
02ac89c
Implement requested PR changes
MatthieuBeukers Apr 14, 2026
646197e
Merge branch 'main' of https://github.com/molgenis/vip into feat/add_…
MatthieuBeukers Apr 16, 2026
File filter

Filter by extension

Filter by extension
Conversations
Failed to load comments.
Loading
Jump to
Jump to file
Failed to load files.
Loading
Diff view
Diff view
192 changes: 123 additions & 69 deletions docs/advanced/annotations.md
View file
Open in desktop

Large diffs are not rendered by default.

10 changes: 6 additions & 4 deletions docs/usage/workflow.md
View file
Open in desktop
Original file line number Diff line number Diff line change
Expand Up @@ -144,18 +144,20 @@ cn6-->cn7
end
subgraph "Subworkflow: mitochondrial snv"
cm0[Mutect2]
cm1[Merge VCF]
cm1t[(<b>per project:</b><br>project_mtdnasnv.vcf.gz)]
cm1[FilterMutectCalls]
cm2[Merge VCF]
cm2t[(<b>per project:</b><br>project_mtdnasnv.vcf.gz)]
cm0-->cm1
cm1-->cm1t
cm1-->cm2
cm2-->cm2t
end
cs0{Mitochondrial?}
cs1[Merge SNV VCF]
cs2[(<b>per project:</b><br>project_complete_snv.vcf.gz)]
cs0-->|"false"|cn0
cs0-->|"true"|cm0
cn7-->cs1
cm1-->cs1
cm2-->cs1
cs1-->cs2
end
subgraph "Subworkflow: str"
Expand Down
8 changes: 5 additions & 3 deletions modules/cram/gatk.nf
View file
Open in desktop
Original file line number Diff line number Diff line change
Expand Up @@ -13,14 +13,14 @@ process mutect2_mito {
chrmName = params.mt[meta.project.assembly].chrm_name

vcfOut = "${meta.project.id}_${meta.sample.family_id}_${meta.sample.individual_id}_chrm_snv.vcf.gz"
vcfOutIndex = "${vcfOut}.csi"
vcfOutIndex = "${vcfOut}.tbi"
vcfOutStats = "${vcfOut}.stats"

template 'mutect2_mito.sh'

stub:
vcfOut="${meta.project.id}_${meta.sample.family_id}_${meta.sample.individual_id}_chrm_snv.vcf.gz"
vcfOutIndex="${vcfOut}.csi"
vcfOutIndex="${vcfOut}.tbi"
vcfOutStats="${vcfOut}.stats"

"""
Expand All @@ -34,7 +34,7 @@ process filtermutect2_mito {
label 'gatk_filtermutect2_mito'

input:
tuple val(meta), path(vcf), path(vcfIndex)
tuple val(meta), path(vcf), path(vcfIndex), path(vcfStats)

output:
tuple val(meta), path(vcfOut), path(vcfOutIndex), path(vcfOutStats)
Expand All @@ -47,6 +47,8 @@ process filtermutect2_mito {
vcfOutIndex = "${vcfOut}.csi"
vcfOutStats = "${vcfOut}.stats"

template 'filtermutect2_mito.sh'

stub:
vcfOut = "${meta.project.id}_${meta.sample.family_id}_${meta.sample.individual_id}_chrm_snv.filtered.vcf.gz"
vcfOutIndex = "${vcfOut}.csi"
Expand Down
29 changes: 27 additions & 2 deletions modules/cram/templates/filtermutect2_mito.sh
View file
Open in desktop
Original file line number Diff line number Diff line change
Expand Up @@ -3,23 +3,48 @@ filtermutect2 () {
filtermutect_args+=("-Djava.io.tmpdir=${TMPDIR}")
filtermutect_args+=("-XX:ParallelGCThreads=2")
filtermutect_args+=("-Xmx!{task.memory.toMega() - 512}m")
filtermutect_args+=("-jar” “/opt/gatk/lib/gatk.jar")
filtermutect_args+=("-jar" "/opt/gatk/lib/gatk.jar")
filtermutect_args+=("FilterMutectCalls")
filtermutect_args+=("-R" "!{reference}")
filtermutect_args+=("-V" "!{vcf}")
filtermutect_args+=("-O" "!{vcfOut}")
filtermutect_args+=("-O" "tmp_results.vcf.gz")
filtermutect_args+=("--mitochondria-mode")
filtermutect_args+=("--stats" "!{vcfStats}")
filtermutect_args+=("--max-alt-allele-count" "4")

${CMD_GATK} java "${filtermutect_args[@]}"
}

index () {
${CMD_BCFTOOLS} index --csi "!{vcfOut}"
${CMD_BCFTOOLS} index --tbi "!{vcfOut}"
${CMD_BCFTOOLS} stats "!{vcfOut}" > "!{vcfOutStats}"
}

# Work around for issue described here: https://github.com/broadinstitute/gatk/issues/6857
fix_vcf () {
gunzip -c "tmp_results.vcf.gz" | sed 's|##INFO=<ID=AS_FilterStatus,Number=A,Type=String,Description="Filter status for each allele, as assessed by ApplyVQSR. Note that the VCF filter field will reflect the most lenient/sensitive status across all alleles.">|##INFO=<ID=AS_FilterStatus,Number=.,Type=String,Description="Filter status for each allele, as assessed by ApplyVQSR. Note that the VCF filter field will reflect the most lenient/sensitive status across all alleles.">|' > "tmp_filtered.vcf"
${CMD_BGZIP} "tmp_filtered.vcf"
mv "tmp_filtered.vcf.gz" "!{vcfOut}"
}

tmp_index () {
${CMD_BCFTOOLS} index --csi "tmp_results.vcf.gz"
}

cleanup () {
mv "tmp_results.vcf.gz.filteringStats.tsv" "!{vcfOut}.filteringStats.tsv"
rm -f "tmp_results.vcf.gz"
rm -f "tmp_results.vcf.gz.csi"
rm -f "tmp_results.vcf.gz.tbi"
}

main () {
trap 'rc=$?; cleanup; exit $rc' EXIT INT TERM

filtermutect2
tmp_index
fix_vcf
index
}

Expand Down
1 change: 0 additions & 1 deletion modules/cram/templates/mutect2_mito.sh
View file
Open in desktop
Original file line number Diff line number Diff line change
Expand Up @@ -17,7 +17,6 @@ mutect2 () {

index () {
${CMD_BCFTOOLS} index --csi "!{vcfOut}"
${CMD_BCFTOOLS} stats "!{vcfOut}" > "!{vcfOutStats}"
}

main () {
Expand Down
8 changes: 7 additions & 1 deletion subworkflows/call_mtdna_snv.nf
View file
Open in desktop
Original file line number Diff line number Diff line change
@@ -1,7 +1,7 @@
nextflow.enable.dsl=2

include { nrMappedReads } from '../modules/cram/utils'
include { mutect2_mito } from '../modules/cram/gatk.nf'
include { mutect2_mito; filtermutect2_mito } from '../modules/cram/gatk.nf'
include { merge_mtdnasnv_vcf } from '../modules/cram/merge_vcf.nf'
include { publish_mtdna_vcf } from '../modules/cram/publish_mtdna_vcf.nf'
include { validateGroup } from '../modules/utils'
Expand All @@ -25,6 +25,12 @@ workflow mtdnasnv {
| map { meta -> [meta, meta.sample.cram.data, meta.sample.cram.index] }
| mutect2_mito
| map { meta, vcfOut, vcfOutIndex, vcfOutStats -> [meta, [data: vcfOut, index: vcfOutIndex, stats: vcfOutStats]] }
| set { ch_mtdnasnv_gatk_unfiltered }

ch_mtdnasnv_gatk_unfiltered
| map { meta, vcf -> [meta, vcf.data, vcf.index, vcf.stats] }
| filtermutect2_mito
| map { meta, vcfOut, vcfOutIndex, vcfOutStats -> [meta, [data: vcfOut, index: vcfOutIndex, stats: vcfOutStats]] }
Copy link
Copy Markdown
Member

@bartcharbon bartcharbon Apr 10, 2026

Choose a reason for hiding this comment

The reason will be displayed to describe this comment to others. Learn more.

Update the workflow diagram in the docs

| set { ch_mtdnasnv_gatk }

// Group the vcfs per project
Expand Down