I have a callset from cancer NGS data (tumor/normal design, ~100 samples) and I have CNVs called there. Additional complexity is - some samples are close to tri- and tetra-ploid state.
I study impact of genomic variants on therapy response.
In some papers I've met definition "ploidy corrected CNVs" - but without clear explanation how it was done. If I understood correctly, people take average ploidy across the genome and consider everything that is below 0.5 copies below this baseline as deletion and 0.5 above the ploidy baseline as duplication. So diploid gene X in tetraploid sample is considered as largely deleted.
1) How to correctly perform ploidy correction?
2) Should we correct for ploidy for largely deleterious tumors? E.g. where average ploidy is 1.5 (half of genome was deleted). Common sense tells me that no, but I wander if it is correct.
3) Bonus question: do you know btw how to take clonality (expressed as cancer cell fraction) of variant into account? Duplication in 10% of cells seems to affect therapy response less than duplication in 90%. But I also doubt that effect of CCF is linear.
upd: there is a related question, Ploidy in copy number analysis , however it is not exactly about this. The answer in the question is "Otherwise, I agree with you, calling relative to ploidy doesn't make a lot of sense biologically." - but I see that what is important is relative gene dosage, not absolute, and if everything is tetraploid - we may expect some sort of gene product balancing there.
Upd1: I apologize for wrong usage of terminology and I am blocked from any responses until tomorrow since I have reached 5 posts limit on this website.