Filtering variants after calling on intervals - VQSR vs Hard-filter vs CNN

MehulS

Hi. I have ~80-100 low-coverage (5-10X) WGS samples which I want to run through a joint genotyping (GVCF) workflow. I have "Halotype-called" (ERC GVCF) variants on my genes of interest using an interval list (contains 90 genes).

Will VQSR work with the final interval-subsetted VCF ? If no, would it help if I extended my intervals to cover a 100 more genes and extend the intervals further ? I'm very reluctant to call variants on the whole genome samples since I'm in a hurry and HaplotypeCaller takes too long (~6 hours).

PS I have one high coverage sample which I can download but would prefer not to.

Apart from that I have previously made calls on the same samples (but over the whole genome) by which I plan to use in my training set.

bhanuGandham

@MehulS

yes that should work.

bhanuGandham

HI @MehulS

Will VQSR work with the final interval-subsetted VCF ?

I don't see why not

MehulS

Thank you for your reply @bhanuGandham . I am concerned because VQSR needs a lot of variants to build a model while my resulting raw variants will be restricted to my intervals which I have called the variants on. Is there any specific threshold for the minimum amount of variants VQSR needs to build a good model, or at least work ?

MehulS

Update: I did a round of genotype GVCFs on 85 samples and got 12180423 variants. Is this good enough for VQSR to at least work ?

bhanuGandham

@MehulS

yes that should work.