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SBIMB / StellarPGx

Calling star alleles in highly polymorphic pharmacogenes (e.g. CYP450 genes) by leveraging genome graph-based variant detection.
MIT License
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TPMT genotypes #35

Closed lisosome closed 3 months ago

lisosome commented 3 months ago

Hi there!

Thanks for the great tool!

I've performed TPMT calling from WGS data. I was wondering, what is the meaning of certain alleles? Like 1S. Are they functionally similar to 1?

Moreover, some samples are called as 1/3A or 3B/3C. Does that mean that the individual has or the 1/3A or the 3B/3C. diplotype, or that the 3A allele can be 3B or *3C?

Thanks in advance! Giuseppe

twesigomwedavid commented 3 months ago

Hi @lisosome,

Thanks for reaching out and for using the tool. As you may know, TPMT hasn't yet been added into the PharmVar database.

Tabell_over_TPMT-alleler_LiU_2022.pdf

I have attached a table with a summary of TPMT allele nomenclature. As you can see, it includes alleles such as 1S. This allele is most likely similar in function to 1, so it should be ok to consider the frequency of 1 as the total of 1 + *1S calls.

Also, from the nomenclature, 1/3A and 3B/3C diplotypes are denoted by the same variant combination (GRCh38: 18130687~T>C~0/1;18138983~G>A~1/1;18138997~C>T~0/1), which is why it's difficult for StellarPGx to tell them apart. However, 1/3A is more common, so it's probably better to err on the side of this diplotype. If you would like to get some more phasing information to tell these diplotypes apart, I'd recommend using the VCF files in the variants output folder to create a merged VCF, which you can then phase using tools such as SHAPEIT (https://odelaneau.github.io/shapeit5/).

lisosome commented 3 months ago

Hi @twesigomwedavid,

Thanks for all the info and the detailed response. This was very helpful!

Best, Giuseppe