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question about re-aligning reads in GATK workflow
Hi GATK Team,
I am using GATK tools and MuTect to call mutations from whole genome sequencing data that I got from the TCGA. A co-worker in the lab suggested that I revert the TCGA .bam files to fastqs and re-do the alignment to the same reference build, so that the mutation calls will be comparable.
For very large .bam files (>100 GB), I am finding the re-alignment step to be a bottle-neck in the pipeline (is taking more than 2 days), so I am trying to figure out whether this step is essential. Sorry if this is a naive question; I was wondering if there are any disadvantages to avoiding this step, and instead, directly using the .bam files as input into the next step in the pipeline, which is local realignment with the RealignmentTargetCreator and IndelRealigner? I understand the resulting mutation calls cannot be directly compared if the reads are aligned to different reference builds, but I've read of some tools such as the UCSC LiftOver (http://genome.ucsc.edu/FAQ/FAQdownloads.html#download28) that seem to solve this problem. Is there something else I'm missing?
Thanks very much for your time,