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PON filtering logic and tag in vcf.gz file #9035

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YuanTian1991 opened this issue Nov 7, 2024 · 0 comments
Open

PON filtering logic and tag in vcf.gz file #9035

YuanTian1991 opened this issue Nov 7, 2024 · 0 comments

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@YuanTian1991
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YuanTian1991 commented Nov 7, 2024

Hi GATK Team:

I have some questions about the application of PON in GATK Mutect2. I have run some samples with and without PON (other parameters are exactly the same). The vcf.gz file from with-PON have less than 20K sites in chr22.

PON Tag in vcf.gz file

However, In the vcf.gz file I received from with-PON option, there are also some sites with PON tag? Why they are not removed? Looks to me, some sites in PON will be directly removed and not reported in the vcf.gz file, while some sites will be reported but contains PON tag (in below screenshot). Why is that?

image

I think I found the explanation here:

image

So these are sites in active regions but also in PON. So I believe they should also be filtered out right?

is the PON filtering is allele-specific?

I found an question 5 years ago here. In this answer, it seems PON filtering in Mutect2 is NOT allele-specific. How is it now?

The logic behind PON filtering.

Third, I want to confirm the logic behind PON filtering. I believe it's only based on coordinates right? There is no statistic behind, if a site in variant calling is overlapped with a site in PON, it will be removed, or labelled as PON in the reported vcf.gz file.

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