how to set parameters value in DepthOfCoverage matched the default value in mutect2

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JUNHUI LI

• November 01, 2024 20:16

Hi there,

I am planning to normalize the somatic mutation rate across samples using DepthOfCoverage. To maintain consistency with Mutect2, which uses --min-base-quality-score of 10 and --base-quality-score-threshold of 18, I am uncertain about the appropriate value to set for --min-base-quality in DepthOfCoverage (which defaults to 0). Google AI suggested that using --min-base-quality 0 would be sufficient, but I’m confused about how these values align. I noticed that the Read Filters used in Mutect2 and DepthOfCoverage differ. Could this impact the final output?

I would greatly appreciate guidance on how to correctly set this parameter. 

Thanks,

Junhui

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  Gökalp Çelik

  • November 04, 2024 17:57

  Hi JUNHUI LI

  Allelic depths and coverages produced by Mutect2 is not 1:1 comparable to DepthOfCoverage tool since Mutect2 is utilizing reassembly and realignment. During these steps Mutect2 determines useful and informative reads for the variant and decides for the values. DepthOfCoverage on the other hand does not have such measures to decide which read is informative therefore the only thing you can do is to limit mapping and base qualities and ignore any duplicate/secondary or supplementary reads in counting read depth. 

  I hope this helps. 

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  JUNHUI LI

  • November 04, 2024 18:08

  Thanks for the clarification, Gökalp Çelik .

  Is there a feature in GATK that can perform this normalization?

  Thanks,
  Junhui

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  Gökalp Çelik

  • November 04, 2024 18:37

  If  you are talking about read filters such as wellformed read filter, not duplicate read filter etc those are available to all tools. 

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