Hi,
I am interested in H3K9me2 signal (in S. Pombe), which is abundant on telomeres and centromeres. These regions are notorious for being highly repetitive. I clearly see an effect between treated and control samples in the coverage on telomeres, and I would like to quantify these differences using csaw. However, I think that he default normalisation (TMM) is problematic, because if I have more signal from the telomeres, then I also have more multi-mapping reads (because they fall on repeats), the multi-mappers are not counted, which affects the the over-all count normalisation.
Any thoughts on how to solve this? Maybe skip TMM and divide the counts by the total number of mapped reads (not just the uniquely mapped)?
Thanks,
Gil Hornung
Thanks Aaron!