Can I annotate a 32GB vcf file containing 300 samples at once using ANNOVAR?

Question

[christinacanavati2014]

I have a 32 GB VCF file containing 300 samples. I also have access to a cluster computing system. Do you recommend annotating this large file all at once, or splitting it to two files (150 samples each) and annotating?

Any suggestions on how much CPU and RAM this should require?

Thank you!

Answer 1

[Ram]

Annovar and such tools (VEP, snpEff) annotate sites, not samples. A 300 sample VCF will definitely have a LOT of variant sites. It might take annovar a week (if not more) to annotate even if it's using a 64-128GB RAM node. If you'd like to make progress in chunks, split the VCF per chromosome and process each chromosome separately, then concat the VCFs. That way, you can have a bunch of parallel runs.