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)?