I have a VCF file with 24 control samples and 24 treated sample all called jointly through GATK. I am not interested in the differences between all my samples vs ensembl reference used for mapping. I am interested in control vs treated. So I would like to use my control samples as reference and regenotype my treated samples against it.
To explain further, here is a simplified example:
var ref alt t1 t2 t3 c1 c2 c3 1 A T A/T A/T A/T A/T A/T A/T 2 A T A/T A/T A/T A/A A/A A/A 3 G C G/G G/G G/G G/C G/C G/C
var1 would not be interesting as it does not differ between controls and treated. var2 and var3 are interesting.
I am thinking of an approach where I would pick variants that have identical genotypes across controls and find a consensus. Then use that as the reference and regenotype my treated samples against it. Now that brings us to an interesting question... Which allele do I pick as reference for heterozygous positions. Now sure how they do that for all the reference genomes...
In this example, I am just going to pick the most common allele for each variant and set that as the reference. var1 was skipped earlier and the new reference looks like:
var ref 2 A 3 G
Now if we regenotype the treated samples against the new reference, we get:
var ref alt c1 c2 c3 2 A A A/A A/A A/A 3 G C G/C G/C G/C
var 2 can be skipped because it is not polymorphic anymore (only because A was chosen as ref). Then we have:
var ref alt c1 c2 c3 3 G C G/C G/C G/C
Is this correct? Anything like this implemented in any workflow/software? Ultimately the aim is to pick only differences caused due to the experimental condition.