# HG changeset patch # User dave # Date 1569504203 14400 # Node ID c27f4eb641bff73fa0fd9703965881c8fcd139a7 Uploaded diff -r 000000000000 -r c27f4eb641bf gatk4_Mutect2.xml --- /dev/null Thu Jan 01 00:00:00 1970 +0000 +++ b/gatk4_Mutect2.xml Thu Sep 26 09:23:23 2019 -0400 @@ -0,0 +1,551 @@ + + - Call somatic SNVs and indels via local assembly of haplotypes + + macros.xml + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + output_opt['activity_profile_out_sel'] + + + output_opt['assembly_region_out_sel'] + + + output_opt['bam_output_sel'] + + + output_opt['graph_output_sel'] + + + + + + `__) +with the assembly-based machinery of +`HaplotypeCaller `__. + +This tool is featured in the *Somatic Short Mutation calling Best +Practice Workflow*. See +`Tutorial#11136 `__ +for a step-by-step description of the workflow and +`Article#11127 `__ +for an overview of what traditional somatic calling entails. For the +latest pipeline scripts, see the `Mutect2 WDL scripts +directory `__. +Although we present the tool for somatic calling, it may apply to other +contexts, such as mitochondrial variant calling. + +Usage examples +~~~~~~~~~~~~~~ + +Example commands show how to run Mutect2 for typical scenarios. The two +modes are (i) *somatic mode* where a tumor sample is matched with a +normal sample in analysis and (ii) *tumor-only mode* where a single +sample's alignment data undergoes analysis. + +(i) Tumor with matched normal +^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ + +Given a matched normal, Mutect2 is designed to call somatic variants +only. The tool includes logic to skip emitting variants that are clearly +present in the germline based on provided evidence, e.g. in the matched +normal. This is done at an early stage to avoid spending computational +resources on germline events. If the variant's germline status is +borderline, then Mutect2 will emit the variant to the callset for +subsequent filtering and review. + +:: + + gatk Mutect2 \ + -R reference.fa \ + -I tumor.bam \ + -tumor tumor_sample_name \ + -I normal.bam \ + -normal normal_sample_name \ + --germline-resource af-only-gnomad.vcf.gz \ + --af-of-alleles-not-in-resource 0.00003125 \ + --panel-of-normals pon.vcf.gz \ + -O somatic.vcf.gz + + +The --af-of-alleles-not-in-resource argument value should match +expectations for alleles not found in the provided germline resource. +Note the tool does not require a germline resource nor a panel of +normals (PoN) to run. The tool prefilters sites for the matched normal +and the PoN. For the germline resource, the tool prefilters on the +allele. Below is an excerpt of a known variants resource with population +allele frequencies + +:: + + #CHROM POS ID REF ALT QUAL FILTER INFO + 1 10067 . T TAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCC 30.35 PASS AC=3;AF=7.384E-5 + 1 10108 . CAACCCT C 46514.32 PASS AC=6;AF=1.525E-4 + 1 10109 . AACCCTAACCCT AAACCCT,* 89837.27 PASS AC=48,5;AF=0.001223,1.273E-4 + 1 10114 . TAACCCTAACCCTAACCCTAACCCTAACCCTAACCCCTAACCCTAACCCTAACCCTAACCCTAACCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCCTAACCCTAACCCTAAACCCTA *,CAACCCTAACCCTAACCCTAACCCTAACCCTAACCCCTAACCCTAACCCTAACCCTAACCCTAACCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCCTAACCCTAACCCTAAACCCTA,T 36728.97 PASS AC=55,9,1;AF=0.001373,2.246E-4,2.496E-5 + 1 10119 . CT C,* 251.23 PASS AC=5,1;AF=1.249E-4,2.498E-5 + 1 10120 . TA CA,* 14928.74 PASS AC=10,6;AF=2.5E-4,1.5E-4 + 1 10128 . ACCCTAACCCTAACCCTAAC A,* 285.71 PASS AC=3,1;AF=7.58E-5,2.527E-5 + 1 10131 . CT C,* 378.93 PASS AC=7,5;AF=1.765E-4,1.261E-4 + 1 10132 . TAACCC *,T 18025.11 PASS AC=12,2;AF=3.03E-4,5.049E-5 + + +(ii) Tumor-only mode +^^^^^^^^^^^^^^^^^^^^ + +This mode runs on a single sample, e.g. single tumor or single normal +sample. To create a PoN, call on each normal sample in this mode, then +use CreateSomaticPanelOfNormals to generate the PoN. + +:: + + gatk Mutect2 \ + -R reference.fa \ + -I sample.bam \ + -tumor sample_name \ + -O single_sample.vcf.gz + + +Further points of interest +~~~~~~~~~~~~~~~~~~~~~~~~~~ + +Additional parameters that factor towards filtering, including +normal-artifact-lod (default threshold 0.0) and tumor-lod (default +threshold 5.3), are available in FilterMutectCalls. While the tool +calculates normal-lod assuming a diploid genotype, it calculates +normal-artifact-lod with the same approach it uses for tumor-lod, i.e. +with a variable ploidy assumption. + +- If the normal artifact log odds becomes large, then FilterMutectCalls applies the artifact-in-normal filter. For matched normal samples with tumor contamination, consider increasing the normal-artifact-lod threshold. + +- The tumor log odds, which is calculated independently of any matched normal, determines whether to filter a tumor variant. Variants with tumor LODs exceeding the threshold pass filtering. + + +If a variant is absent from a given germline resource, then the value +for --af-of-alleles-not-in-resource applies. For example, gnomAD's +16,000 samples (~32,000 homologs per locus) becomes a probability of one +in 32,000 or less. Thus, an allele's absence from the germline resource +becomes evidence that it is not a germline variant. + +Caveats +~~~~~~~ + +Although GATK4 Mutect2 accomodates varying coverage depths, further +optimization of parameters may improve calling for extreme high depths, +e.g. 1000X. +]]> + + + + diff -r 000000000000 -r c27f4eb641bf macros.xml --- /dev/null Thu Jan 01 00:00:00 1970 +0000 +++ b/macros.xml Thu Sep 26 09:23:23 2019 -0400 @@ -0,0 +1,710 @@ + + + 4.0.5.1 + @VERSION@+galaxy + + + + gatk4 + tabix + samtools + + + + + + + gatk SortSam --version 2>&1 | grep Version | cut -d ':' -f 2 + + + + gatk --java-options "\$_JAVA_OPTIONS" + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + + + + + + + + + +
+
+ + + + + + + + + + not gzipped_output + + + gzipped_output + + + + + + + + + + + + picard_adv['CREATE_MD5_FILE'] + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 10.1101/gr.107524.110 + 10.1038/ng.806 + 10.1002/0471250953.bi1110s43 + 10.1101/201178 + + + +
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