Hi GATK team,
Hope you had great holidays!
We're analyzing small families where some individual have been sequenced by WES (HiSeqX) and others by WES (HiSeq4000). Could you please advise on the best approach to variant discovery and genotyping for these sets. We prefer to avoid the difficult normalization of the different vcf representations of identical variants that results when the WES|WGS sets are analyzed separately.
Our best idea so far is to run HC over mostly overlapping intervals (eg GenCode exons) on all individual samples in both sets, then jointly genotype the mixed g.vcfs (GenotypeGVCFs) - accepting that there will be some ./. calls in each set.
Also, could VQSR cope with the mixed variant properties?
We noticed that @Geraldine_VdAuwera has advised against a similar idea earlier this year (http://gatkforums.broadinstitute.org/wdl/discussion/6834/about-gatk-joint-call), but that was more complex (WES+WGS+RNAseq) and of course you may have looked into this since then.
Thanks in advance for your thoughts and advice