Rare Allele Discovery

[sidevshiy]

Hello,

I have a couple of questions about the functionality available in PHG. Specifically, I am interested in whether there is a way to extract imputed VCFs that contain SNP variances. Could you please provide guidance on how to achieve this if it is possible?

In your architecture diagram, there is a section labeled "Rare Allele Discovery," which is also mentioned in the description of the phg create-fasta-from-hvcf command. As I understand it, this process (including aligning and using GATK) needs to be performed manually. Is my understanding correct? Additionally, are there any plans to integrate this process into the PHG workflow?

[lynnjo]

The Rare Allele Discovery pipeline is still under development. We are determining the best ways to approach this and do not yet have commands for it.

In terms of imputed VCFs: There is a command named "hvcf2gvcf" that takes the hvcf file created from the imputed path and turns it into a g.vcf. This should give you the variants you seek.

[lynnjo]

The gvcf file created in the hvcf2gvcf command pulls the data from the original gvcf files previously stored in the db. Can you verify the existing (original) gvcf files have the correct value at those positions?

[sidevshiy]

Yes, when I run this command (bcftools norm --check-ref w --fasta-ref /path/to/Ref.fa path/to/gvcf/sample.g.vcf -o test.vcf) with gvcfs (actually the extentions is vcf when it pull those anchorwave alignmets from db) it doesn't give me a warnings and positions are correct. hvcf files also have correct positions. I believe that there is an error in hvcf2gvcf command.

[lynnjo]

ok - I will take a look at this.

[lynnjo]

hi @sidevshiy
I have found and committed a fix for the wrong ref allele problem. The fix is in the current version of phgv2 (2.3.15.152). WIll you check this out and verify it works for you? Thanks for all your feedback.

[sidevshiy]

@lynnjo Hello, sorry for long time with no answer. Yes, it works now. Thank you!