Training data mode in Mutect2 to prepare for Mutect3

broadinstitute · May 4, 2021 · 29e658c · 29e658c
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diff --git a/scripts/mutect2_wdl/mutect3_training_data.wdl b/scripts/mutect2_wdl/mutect3_training_data.wdl
@@ -0,0 +1,272 @@
+version 1.0
+
+import "https://raw.githubusercontent.com/gatk-workflows/gatk4-somatic-snvs-indels/2.6.0/mutect2.wdl" as m2
+
+workflow Mutect3TrainingData {
+    input {
+        File? intervals
+        File? masks
+        File ref_fasta
+        File ref_fai
+        File ref_dict
+        Int scatter_count
+        File tumor_bam
+        File tumor_bai
+        File? normal_bam
+        File? normal_bai
+        File? pon
+        File? gnomad
+        File? variants_for_contamination
+        String ref_downsample
+        Boolean? run_orientation_bias_mixture_model_filter
+        File? realignment_index_bundle
+        String? realignment_extra_args
+        String? m2_extra_args
+        String? m2_extra_filtering_args
+        File? truth_vcf
+        File? truth_vcf_idx
+        Boolean? make_bamout
+
+        # runtime
+        String gatk_docker
+        File? gatk_override
+        Int? preemptible
+        Int? max_retries
+    }
+
+    String m2_extra_args_with_training_mode = select_first([m2_extra_args, ""]) + " --training-data-mode --training-data-mode-ref-downsample " + ref_downsample
+
+    # call on the tumor (with normal if present) to get tumor read data and M2 filtering
+    call m2.Mutect2 as Tumor {
+        input:
+            ref_fasta = ref_fasta,
+            ref_fai = ref_fai,
+            ref_dict = ref_dict,
+            scatter_count = scatter_count,
+            tumor_reads = tumor_bam,
+            tumor_reads_index = tumor_bai,
+            normal_reads = normal_bam,
+            normal_reads_index = normal_bai,
+            intervals = intervals,
+            pon = pon,
+            gnomad = gnomad,
+            variants_for_contamination = variants_for_contamination,
+            run_orientation_bias_mixture_model_filter = run_orientation_bias_mixture_model_filter,
+            realignment_index_bundle = realignment_index_bundle,
+            realignment_extra_args = realignment_extra_args,
+            preemptible = preemptible,
+            max_retries = max_retries,
+            m2_extra_args = m2_extra_args_with_training_mode,
+            m2_extra_filtering_args = m2_extra_filtering_args,
+            make_bamout = make_bamout,
+            gatk_override = gatk_override,
+            gatk_docker = gatk_docker
+    }
+
+    if(defined(truth_vcf)) {
+        call Concordance  {
+            input:
+                intervals = intervals,
+                masks = masks,
+                truth_vcf = select_first([truth_vcf]),
+                truth_vcf_idx = select_first([truth_vcf_idx]),
+                eval_vcf = Tumor.filtered_vcf,
+                eval_vcf_idx = Tumor.filtered_vcf_idx,
+                preemptible = preemptible,
+                gatk_override = gatk_override,
+                gatk_docker = gatk_docker
+        }
+
+        call MakeTableFromConcordance as TumorConcordanceTable {
+            input:
+                tpfp = Concordance.tpfp,
+                tpfp_idx = Concordance.tpfp_idx,
+                ftnfn = Concordance.ftnfn,
+                ftnfn_idx = Concordance.ftnfn_idx,
+                gatk_override = gatk_override,
+                gatk_docker = gatk_docker,
+                preemptible = preemptible
+        }
+    }
+
+    if(!defined(truth_vcf)) {
+        call MakeTableFromMutect2 as TumorTable {
+            input:
+                filtered_vcf = Tumor.filtered_vcf,
+                filtered_vcf_idx = Tumor.filtered_vcf_idx,
+                gatk_override = gatk_override,
+                gatk_docker = gatk_docker,
+                preemptible = preemptible
+        }
+    }
+
+    # call on the normal, with tumor as "matched normal", to get normal read data and M2 filtering
+    if(defined(normal_bam)) {
+        call m2.Mutect2 as Normal {
+            input:
+                ref_fasta = ref_fasta,
+                ref_fai = ref_fai,
+                ref_dict = ref_dict,
+                scatter_count = scatter_count,
+                tumor_reads = select_first([normal_bam]),
+                tumor_reads_index = select_first([normal_bai]),
+                normal_reads = tumor_bam,
+                normal_reads_index = tumor_bai,
+                intervals = intervals,
+                pon = pon,
+                gnomad = gnomad,
+                variants_for_contamination = variants_for_contamination,
+                run_orientation_bias_mixture_model_filter = run_orientation_bias_mixture_model_filter,
+                realignment_index_bundle = realignment_index_bundle,
+                realignment_extra_args = realignment_extra_args,
+                preemptible = preemptible,
+                max_retries = max_retries,
+                m2_extra_args = m2_extra_args_with_training_mode,
+                m2_extra_filtering_args = m2_extra_filtering_args,
+                make_bamout = make_bamout,
+                gatk_override = gatk_override,
+                gatk_docker = gatk_docker
+        }
+
+        # there's no reason to call concordance on the normal because the calls will have no relation to the truth VCF
+
+        call MakeTableFromMutect2 as NormalTable {
+            input:
+                filtered_vcf = Normal.filtered_vcf,
+                filtered_vcf_idx = Normal.filtered_vcf_idx,
+                gatk_override = gatk_override,
+                gatk_docker = gatk_docker,
+                preemptible = preemptible
+        }
+    }
+
+
+
+
+    output {
+        File tumor_table = select_first([TumorConcordanceTable.table, TumorTable.table])
+        File? normal_table = NormalTable.table
+    }
+}
+
+task Concordance {
+    input {
+        File? intervals
+        File? masks
+        File truth_vcf
+        File truth_vcf_idx
+        File eval_vcf
+        File eval_vcf_idx
+
+        File? gatk_override
+
+        # runtime
+        String gatk_docker
+        Int? preemptible
+    }
+
+    command {
+        export GATK_LOCAL_JAR=${default="/root/gatk.jar" gatk_override}
+
+        gatk --java-options "-Xmx2g" Concordance \
+        ~{"-L " + intervals} \
+        ~{"-XL " + masks} \
+        -truth ~{truth_vcf} -eval ~{eval_vcf} \
+        -tpfp "tpfp.vcf" \
+        -ftnfn "ftnfn.vcf" \
+        -summary "summary.txt"
+    }
+
+    runtime {
+        memory: "5 GB"
+        bootDiskSizeGb: 12
+        docker: "${gatk_docker}"
+        disks: "local-disk " + 100 + " HDD"
+        preemptible: select_first([preemptible, 2])
+    }
+
+    output {
+        File tpfp = "tpfp.vcf"
+        File tpfp_idx = "tpfp.vcf.idx"
+        File ftnfn = "ftnfn.vcf"
+        File ftnfn_idx = "ftnfn.vcf.idx"
+        File summary = "summary.txt"
+    }
+}
+
+task MakeTableFromMutect2 {
+    input {
+        File filtered_vcf
+        File filtered_vcf_idx
+
+        File? gatk_override
+        String gatk_docker
+        Int? preemptible
+    }
+
+    command {
+        export GATK_LOCAL_JAR=${default="/root/gatk.jar" gatk_override}
+
+        gatk --java-options "-Xmx2g" SelectVariants -V ~{filtered_vcf} --restrict-alleles-to BIALLELIC -O biallelic.vcf
+        gatk --java-options "-Xmx2g" VariantsToTable -V biallelic.vcf \
+          -F CHROM -F POS -F REF -F ALT -F POPAF -F TLOD -F STATUS -F REF_BASES -GF DP -F FILTER -GF FRS \
+          --show-filtered \
+          -O output.table
+    }
+
+    runtime {
+        memory: "5 GB"
+        bootDiskSizeGb: 12
+        docker: "${gatk_docker}"
+        disks: "local-disk " + 100 + " HDD"
+        preemptible: select_first([preemptible, 2])
+    }
+
+    output {
+        File table = "output.table"
+    }
+}
+
+task MakeTableFromConcordance {
+    input {
+        File tpfp
+        File tpfp_idx
+        File ftnfn
+        File ftnfn_idx
+
+        File? gatk_override
+        String gatk_docker
+        Int? preemptible
+    }
+
+    command {
+        export GATK_LOCAL_JAR=${default="/root/gatk.jar" gatk_override}
+
+        for file in ~{tpfp} ~{ftnfn}; do
+            gatk --java-options "-Xmx2g" SelectVariants -V $file --restrict-alleles-to BIALLELIC -O biallelic.vcf
+            gatk --java-options "-Xmx2g" VariantsToTable -V biallelic.vcf \
+              -F CHROM -F POS -F REF -F ALT -F POPAF -F TLOD -F STATUS -F REF_BASES -GF DP -F FILTER -GF FRS \
+              --show-filtered \
+              -O tmp.table
+
+            # if it's the first table, copy it to the output; otherwise copy all but the header line
+            if [ ! -f output.table ]; then
+                mv tmp.table output.table
+            else
+                tail -n +2 tmp.table >> output.table
+            fi
+        done
+    }
+
+    runtime {
+        memory: "5 GB"
+        bootDiskSizeGb: 12
+        docker: "${gatk_docker}"
+        disks: "local-disk " + 100 + " HDD"
+        preemptible: select_first([preemptible, 2])
+    }
+
+    output {
+        File table = "output.table"
+    }
+}
diff --git a/src/main/java/org/broadinstitute/hellbender/tools/walkers/annotator/AlleleFraction.java b/src/main/java/org/broadinstitute/hellbender/tools/walkers/annotator/AlleleFraction.java
@@ -65,9 +65,4 @@ else if (likelihoods != null) {
 
     @Override
     public List<String> getKeyNames() { return Collections.singletonList(GATKVCFConstants.ALLELE_FRACTION_KEY);}
-
-    @Override
-    public List<VCFFormatHeaderLine> getDescriptions() {
-        return Collections.singletonList(GATKVCFHeaderLines.getFormatLine(getKeyNames().get(0)));
-    }
 }