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MuTect2 and VQSR: anyway of calling VQSLOD for MuTect2 ?

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Hello GATK Team ! @Sheila @Geraldine_VdAuwera

Since my last question ( here ), I am trying to build a workflow which can process all my samples with a snakemake workflow. From the previous question testing on samples, I corrected the $line and also more variants "passed" the filtering step by realigning giving the Read Group. I hope that this post can help any person having trouble to run MuTect2 at first. Please correct me if there's anything wrong, I will describe in bullets the steps so far:

  • Align using BWA MEM using FastQ reads --> output in SAM
  • SAM to BAM --> using samtools
  • Sort the BAM --> using Picard
  • Remove duplicates from BAM --> using Picard
  • Add Read Group to BAM --> using Picard
  • Base Recalibration of BAM --> using BaseRecalibrator and PrintReads
  • Indexing BAM --> using samtools
  • Building a PON for BAM --> using MuTect2 in artifact_detection_mode on the normal samples
  • Merge all the PON --> using CombineVariants
  • Run MuTect2 --> Produce raw VCF files with variants that are "PASS"

Following the GATK Best-Practices workflow for Exome Datasets using MuTect2, I am at the last step of variant filtering except if I omitted a step or did a mistake. Following this thread, I assume that there are no further processing but to extract variants that have "PASS" in the VCF files.

I was reading a bit more on the forum when I stumbled upon the VariantRecalibrator for Haplotype Caller (HC). As I understood that this tool assign a new score called VQSLOD which is supposed to be a well-calibrated score that comes from training sets. So I was thinking:

  1. is there's anyway of calling this VQSLOD on the VCF output from MuTect2 ?
  2. Would this produce a more "confident" result to interpret during the analysis of the VCF files of MuTect2 ?
  3. Are you planning to include this option in GATK 4.0 ?

I know the HC is meant for SNPs and indels but being able to produce a VQSLOD for variants on MuTect2 by training sets would supposedly have a more confident result in term of specificity and sensitivity. The only way (as far as I have read) to produce the VQSLOD is by running first the HC on the samples using -ERC GVCF for each sample and then use GenotypeGVCFs on all GVCF files together. Also, I read that the argument for MuTect2 to produce the output in GVCF is not available.

Thank you for your time and effort !

Best regards,
Alaa


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