Combine Multiple Vcf Files / Distinguish Reference Homo And Untyped

Question

[Wen.Huang]

Hi everybody,

I am wondering what is the best approach to deal with sites that are not present in all VCF when combining multiple vcf files. For example, a site may be homozygous for reference in several VCFs. One way is to leave them untyped, as if there are not sufficient coverage. Another way is to assume them as homozygous for reference. A third way may be to look into the alignment files (when they are available). In the last case, how can I be sure that a site is homozygous reference without doing a variant calling?

Thanks!

[Wen.Huang]

I sort of get separate vcf's from different sources

[Sean Davis]

Is there a reason not to call variants in all samples simultaneously?

Answer 1

[thamathpanda]

It's probably not an issue with coverage.

In the last case, how can I be sure that a site is homozygous reference without doing a variant calling?

You might want to look into reading how variants are being called for the platform you are getting your files from. Are you expecting that all called variants would be the same between all individuals?