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Indel Realignment in Tumor-Normal pairs

MilanDMilanD BelgradeMember

Hello dear GATK team,

I have a question regarding indel realignment when doing somatic variant calling (tumor normal pairs). First of all, I am aware that indel realignment is not required by mutect2 but I am still using it for other somatic variant callers. There are a couple of papers mentioning that indel realignment should be done jointly (with both BAMs as input of the RealignerTargetCreator amd IndelRealigner). I tested this using simulated datasets and it did give better results.

I am interested in the reasoning for this, and is this something that should happen in general? In addition, I have a concern regarding differences in coverage. Would this method cause issues if there is a significantly higher coverage in a tumor sample to that in a normal sample?

Thanks in advance!


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