Handling Tumor Purity and Copy Number Correction in ExTRECT for WES Data

[FedericoVann]

Hello,

Thank you for developing such a great tool! I have a question regarding the use of ExTRECT on WES tissue data from a primary tumor with low T cell infiltration.

In my dataset, a fraction of patients shows undetectable tumor purity (~50%), and only a small subset has an estimated copy number for the TCRA region, even though I am confident that the capture kit includes this region.

I am considering running ExTRECT while correcting for purity and copy number whenever possible, but leaving these variables uncorrected when they are unavailable. Would this approach be valid, or could it introduce comparability issues? Alternatively, would it be better to avoid correcting for these variables across all samples to ensure consistency?

I appreciate your insights!

Best regards,

Federico

[rbentham]

Hi Federico,

Sorry for the late response! If I understand you correctly you are wondering how to use T cell ExTRECT on tissues with very low tumour purity where you can not get an accurate estimate of the tumour copy number?

The adjustment formula does not change the calculated fraction in cases where the tumour is diploid at the TCRA locus or the purity is 0 (no tumour present), since these are ultra low purity samples I think you could model it as having a purity of approximately 0 thus leading to an unchanged fraction for these cases. You could model the changes in fraction assuming different tumour copy number and purity levels to see the effect on your data. In cases where the purity is < 0.01 I would expect very little change at even extreme tumour copy number values.

[FedericoVann]

Hello,

Thank you so much for your reply, I will try to do that.

Best regards,

Federico