The frontline support team will be offline as we are occupied with the GATK Workshop on March 21st and 22nd 2019. We will be back and available to answer questions on the forum on March 25th 2019.
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,