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Doesn't Base Quality Score Recalibration degrade sensitivity in heavily mutated cancers?
From the GATK FAQs - "The base quality score recalibrator treats every reference mismatch as indicative of machine error"... which is why we have to give it a list of dbSNPs to skip over. But what about somatic SNPs? Wouldn't hypermutated tumors from uterine, colorectal, melanoma, or lung cancers be re-calibrated to a lower quality than data from AML or breast. And variant caller sensitivity would drop accordingly.
Should we ideally do some high-confidence SNP calling on un-calibrated BAMs, and append those to the dbSNP VCF for the BQSR?