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Joint calling of projects run on different exome-capture platforms
We have some exomes processed with GATK from one exome capture platform (Nimblegen SeqCap on HiSeq), and now I am going to analyze a small batch of exomes sequenced using a different platform (Nextera on NextSeq). I was wondering if and how GenotypeGVCFs can cope with gvcfs produced on two (or more) different exome capture platforms? Is joint-calling of such "heterogeneous" samples advised, or should I rather genotype the small set of equally processed bams separately?
The problems I could foresee were:
- differing targets (each batch of samples will have gaps in coverage due to target-constrained (-L) haplotypecalling). If this should cause problems for GenotypeGVCFs the haplotypes could be called again on superset of targets, or easier, the calling restricted to the intersection.
- the alignment algorithm is different (BWA BWTSW vs BWA MEM) so the mapping quality could potentially differ (haven't checked). Is this something GATK is compensating for, like base qualities?
- the sequencer and chemistry, but here I hope that the BQSR should help in removing the variation
Any thoughts and comments appreciated,