SNP + INDEL Merging Guidelines

Question

[QVINTVS_FABIVS_MAXIMVS]

Say I have SNP INDEL calls for 1000 individuals. These 1000 samples were joint-called and recalibrated with GATK in 10 batches.

As a result I have 10 VCF files with SNP and INDEL calls that I would like to merge. I only have access to the VCF files, so re-calling from the BAMs is not an option.

I'm familiar with bcftools but I'm unclear on the best way forward.

• Should I split multiallelic entries into biallelic before merging?

• If I'm interested in rare variants, should I omit multiallelic variants?

• Should I left align before merging? After merging? Or Both?

Thank you for any advice

[MAPK]

I think your best bet would be to use GATK's merge SNPs option as I had issues merging them using vcftools/bcftools in the past. Possibly this: https://software.broadinstitute.org/gatk/documentation/tooldocs/3.8-0/org_broadinstitute_gatk_tools_walkers_variantutils_CombineVariants.php

[Kevin Blighe]

Yes, I believe GATK's CombineVariants is the answer.