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Challenging Medically Relevant Genes Variant Calling Workflows (WDL)

This section documents the All of Us CMRG workflows for remapping/calling in difficult regions and reblocking gVCFs for downstream joint analysis.

Quick Summary

  • Purpose: Improve variant calling in challenging medically relevant genes and prepare outputs for downstream aggregation.
  • Primary Outputs: Corrected-region VCF/gVCF files and reblocked gVCFs.

Workflow Overviews

StepWorkflowDescriptionWDL
1FixItFelix and Variant CallingSubsets CMRG-relevant reads, remaps to masked GRCh38 using FixItFelix, and runs HaplotypeCaller.WDL
2GVS AoU Reblock gVCFReblocks per-sample gVCFs and optionally copies outputs into AoU site-specific research buckets.WDL

External Downstream Joint Calling

Joint calling can be performed with external GVS workflows, such as:

Suggested Usage Pattern

  1. Run FixItFelix remapping + variant calling (FixItFelixAndVariantCall).
  2. Reblock gVCFs (GvsAoUReblockGvcf) as needed for storage/joint analysis.
  3. Ingest and joint-call using external GVS pipelines.

Feedback

Please help us make our tools better by filing an issue in WARP; we welcome pipeline-related suggestions or questions.