luhuifang / gatk4-somatic-cnvs

Workflows for somatic copy number variant discovery with GATK4

somatic-cnvs

Workflows for somatic copy number variant analysis

Running the Somatic CNV WDL

Which WDL should you use?

• Building a panel of normals (PoN): cnv_somatic_panel_workflow.wdl
• Running a matched pair: cnv_somatic_pair_workflow.wdl

Setting up parameter json file for a run

To get started, create the json template (using java -jar wdltool.jar inputs <workflow>) for the workflow you wish to run and adjust parameters accordingly.

Please note that there are optional workflow-level and task-level parameters that do not appear in the template file. These are set to reasonable values by default, but can also be adjusted if desired.

Required parameters in the somatic panel workflow

Important: The normal_bams samples in the json can be used test the wdl, they are NOT to be used to create a panel of normals for sequence analysis. For instructions on creating a proper PON please refer to user the documents https://software.broadinstitute.org/gatk/documentation/ .

The reference used must be the same between PoN and case samples.

• CNVSomaticPanelWorkflow.gatk_docker -- GATK Docker image (e.g., broadinstitute/gatk:latest).
• CNVSomaticPanelWorkflow.intervals -- Picard or GATK-style interval list. For WGS, this should typically only include the autosomal chromosomes.
• CNVSomaticPanelWorkflow.normal_bais -- List of BAI files. This list must correspond to normal_bams. For example, ["Sample1.bai", "Sample2.bai"].
• CNVSomaticPanelWorkflow.normal_bams -- List of BAM files. This list must correspond to normal_bais. For example, ["Sample1.bam", "Sample2.bam"].
• CNVSomaticPanelWorkflow.pon_entity_id -- Name of the final PoN file.
• CNVSomaticPanelWorkflow.ref_fasta_dict -- Path to reference dict file.
• CNVSomaticPanelWorkflow.ref_fasta_fai -- Path to reference fasta fai file.
• CNVSomaticPanelWorkflow.ref_fasta -- Path to reference fasta file.

In additional, there are optional workflow-level and task-level parameters that may be set by advanced users; for example:

• CNVSomaticPanelWorkflow.do_explicit_gc_correction -- (optional) If true, perform explicit GC-bias correction when creating PoN and in subsequent denoising of case samples. If false, rely on PCA-based denoising to correct for GC bias.
• CNVSomaticPanelWorkflow.PreprocessIntervals.bin_length -- Size of bins (in bp) for coverage collection. This must be the same value used for all case samples.
• CNVSomaticPanelWorkflow.PreprocessIntervals.padding -- Amount of padding (in bp) to add to both sides of targets for WES coverage collection. This must be the same value used for all case samples.

Further explanation of other task-level parameters may be found by invoking the --help documentation available in the gatk.jar for each tool.

Required parameters in the somatic pair workflow

The reference and bins (if specified) must be the same between PoN and case samples.

• CNVSomaticPairWorkflow.common_sites -- Picard or GATK-style interval list of common sites to use for collecting allelic counts.
• CNVSomaticPairWorkflow.gatk_docker -- GATK Docker image (e.g., broadinstitute/gatk:latest).
• CNVSomaticPairWorkflow.intervals -- Picard or GATK-style interval list. For WGS, this should typically only include the autosomal chromosomes.
• CNVSomaticPairWorkflow.normal_bam -- Path to normal BAM file.
• CNVSomaticPairWorkflow.normal_bam_idx -- Path to normal BAM file index.
• CNVSomaticPairWorkflow.read_count_pon -- Path to read-count PoN created by the panel workflow.
• CNVSomaticPairWorkflow.ref_fasta_dict -- Path to reference dict file.
• CNVSomaticPairWorkflow.ref_fasta_fai -- Path to reference fasta fai file.
• CNVSomaticPairWorkflow.ref_fasta -- Path to reference fasta file.
• CNVSomaticPairWorkflow.tumor_bam -- Path to tumor BAM file.
• CNVSomaticPairWorkflow.tumor_bam_idx -- Path to tumor BAM file index.

In additional, there are several task-level parameters that may be set by advanced users as above.

To invoke Oncotator on the called tumor copy-ratio segments:

• CNVSomaticPairWorkflow.is_run_oncotator -- (optional) If true, run Oncotator on the called copy-ratio segments. This will generate both a simple TSV and a gene list.

Further explanation of these task-level parameters may be found by invoking the --help documentation available in the gatk.jar for each tool.