Merge pull request #533 from FriederikeHanssen/issue_509

Issue 509 & 313

.github/workflows/ci.yml

@@ -43,6 +43,7 @@ jobs:
           - "mutect2"
           - "msisensorpro"
           # - 'save_bam_mapped'
+          - "variantcalling_channel"
           - "skip_markduplicates"
           - "strelka"
           - "split_fastq"

CHANGELOG.md

@@ -21,6 +21,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - [#507](https://github.com/nf-core/sarek/pull/507), [#537](https://github.com/nf-core/sarek/pull/537) - Subway map for building indexes
 - [#512](https://github.com/nf-core/sarek/pull/512), [#531](https://github.com/nf-core/sarek/pull/531), [#537](https://github.com/nf-core/sarek/pull/537) - Subway map for pipeline
 - [#522](https://github.com/nf-core/sarek/pull/522) - Add QC for vcf files & MultiQC
+- [#533](https://github.com/nf-core/sarek/pull/533) - Add param `--only_paired_variant_calling` to allow skipping of germline variantcalling for paired samples
 
 ### Changed
 

conf/test.config

@@ -139,6 +139,13 @@ profiles {
     use_gatk_spark {
         params.use_gatk_spark      = 'baserecalibrator,markduplicates'
     }
+    variantcalling_channels {
+        params.input               = "${baseDir}/tests/csv/3.0/recalibrated.csv"
+        params.fasta               = "${params.genomes_base}/data/genomics/homo_sapiens/genome/chr21/sequence/genome.fasta"
+        params.wes                 = true
+        params.step                = 'variant_calling'
+        params.intervals           = "${params.genomes_base}/data/genomics/homo_sapiens/genome/chr21/sequence/multi_intervals.bed"
+    }
 }
 
 //This is apparently useless as it won't overwrite things in the modules.config

nextflow.config

@@ -51,6 +51,7 @@ params {
     sequencing_center = null // No sequencing center to be written in BAM header by aligner
 
     // Variant Calling
+    only_paired_variant_calling = false //if true, skips germline variant calling for normal-paired samples
     ploidy = 2          //null (in ascat, test this works) // Use default value, you can use 2,3,4
     ascat_purity = null // Use default value
     cf_coeff = 0.05                     // default value for Control-FREEC

nextflow_schema.json

@@ -232,6 +232,11 @@
             "default": "",
             "fa_icon": "fas fa-toolbox",
             "properties": {
+                "only_paired_variant_calling": {
+                    "type": "boolean",
+                    "fa_icon": "fas fa-angle-double-right",
+                    "description": "If true, skips germline variant calling for matched normal to tumor sample. Normal samples without matched tumor will still be processed through germline variant calling tools."
+                },
                 "ploidy": {
                     "type": "number",
                     "fa_icon": "fas fa-bacon",

tests/test_only_paired_VC.yml

@@ -0,0 +1,53 @@
+- name: Skip variant calling on matched normal
+  command: nextflow run main.nf -profile test,variantcalling_channels,docker --tools strelka --only_paired_variant_calling
+  tags:
+    - somatic
+    - strelka
+    - variant_calling
+    - variantcalling_channel
+  files:
+    - path: results/variant_calling/sample1/strelka/sample1.variants.vcf.gz
+    - path: results/variant_calling/sample1/strelka/sample1.variants.vcf.gz.tbi
+    - path: results/variant_calling/sample1/strelka/sample1.genome.vcf.gz
+    - path: results/variant_calling/sample1/strelka/sample1.genome.vcf.gz.tbi
+    - path: results/variant_calling/sample3/strelka/sample3.variants.vcf.gz
+      should_exist: false
+    - path: results/variant_calling/sample3/strelka/sample3.variants.vcf.gz.tbi
+      should_exist: false
+    - path: results/variant_calling/sample3/strelka/sample3.genome.vcf.gz
+      should_exist: false
+    - path: results/variant_calling/sample3/strelka/sample3.genome.vcf.gz.tbi
+      should_exist: false
+    - path: results/variant_calling/sample2/strelka/sample2.variants.vcf.gz
+    - path: results/variant_calling/sample2/strelka/sample2.variants.vcf.gz.tbi
+    - path: results/variant_calling/sample2/strelka/sample2.genome.vcf.gz
+    - path: results/variant_calling/sample2/strelka/sample2.genome.vcf.gz.tbi
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_indels.vcf.gz
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_indels.vcf.gz.tbi
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_snvs.vcf.gz
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_snvs.vcf.gz.tbi
+
+- name: Do germline variant calling on matched normal
+  command: nextflow run main.nf -profile test,variantcalling_channels,docker --tools strelka
+  tags:
+    - somatic
+    - strelka
+    - variant_calling
+    - variantcalling_channel
+  files:
+    - path: results/variant_calling/sample1/strelka/sample1.variants.vcf.gz
+    - path: results/variant_calling/sample1/strelka/sample1.variants.vcf.gz.tbi
+    - path: results/variant_calling/sample1/strelka/sample1.genome.vcf.gz
+    - path: results/variant_calling/sample1/strelka/sample1.genome.vcf.gz.tbi
+    - path: results/variant_calling/sample3/strelka/sample3.variants.vcf.gz
+    - path: results/variant_calling/sample3/strelka/sample3.variants.vcf.gz.tbi
+    - path: results/variant_calling/sample3/strelka/sample3.genome.vcf.gz
+    - path: results/variant_calling/sample3/strelka/sample3.genome.vcf.gz.tbi
+    - path: results/variant_calling/sample2/strelka/sample2.variants.vcf.gz
+    - path: results/variant_calling/sample2/strelka/sample2.variants.vcf.gz.tbi
+    - path: results/variant_calling/sample2/strelka/sample2.genome.vcf.gz
+    - path: results/variant_calling/sample2/strelka/sample2.genome.vcf.gz.tbi
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_indels.vcf.gz
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_indels.vcf.gz.tbi
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_snvs.vcf.gz
+    - path: results/variant_calling/sample4_vs_sample3/strelka/sample4_vs_sample3.somatic_snvs.vcf.gz.tbi

workflows/sarek.nf

@@ -627,6 +627,22 @@ workflow SAREK {
         // and remove patient ID field & null value for further processing [meta1, [cram1,crai1]] [meta2, [cram2,crai2]]
         cram_variant_calling_tumor_only = cram_variant_calling_tumor_filtered.transpose().map{ it -> [it[1], it[2], it[3]] }
 
+        if(params.only_paired_variant_calling){
+            // Normal only samples
+
+            // 1. Join with tumor samples, in each channel there is one key per patient now. Patients without matched tumor end up with: [patient1, [meta1], [cram1,crai1], null] as there is only one matched normal possible
+            cram_variant_calling_normal_joined = cram_variant_calling_normal_to_cross.join(cram_variant_calling_tumor_grouped, remainder: true)
+
+            // 2. Filter out entries with last entry null
+            cram_variant_calling_normal_filtered = cram_variant_calling_normal_joined.filter{ it ->  !(it.last()) }
+
+            // 3. Remove patient ID field & null value for further processing [meta1, [cram1,crai1]] [meta2, [cram2,crai2]] (no transposing needed since only one normal per patient ID)
+            cram_variant_calling_status_normal = cram_variant_calling_normal_filtered.map{ it -> [it[1], it[2], it[3]] }
+
+        }else{
+            cram_variant_calling_status_normal = cram_variant_calling_status.normal
+        }
+
         // Tumor - normal pairs
         // Use cross to combine normal with all tumor samples, i.e. multi tumor samples from recurrences
         cram_variant_calling_pair = cram_variant_calling_normal_to_cross.cross(cram_variant_calling_pair_to_cross)
@@ -643,7 +659,7 @@ workflow SAREK {
 
         // GERMLINE VARIANT CALLING
         GERMLINE_VARIANT_CALLING(
-            cram_variant_calling_status.normal,
+            cram_variant_calling_status_normal,
             dbsnp,
             dbsnp_tbi,
             dict,