# Is it okay to use deeptools bamCompare (SES normalization) for comparisons across different ATAC-Seq datasets?

We are trying to use deeptools for analysis of ATAC Seq datasets. We have datasets with different sequencing depths and are wondering if bamCompare's SES based normalization is appropriate for comparing two ATACSeq datasets as opposed to ChipSeq datasets. If such normalization is okay to perform, does it make sense to compare difference in values across comparisons? Let's say I do bamCompare on A and B using SES, and then I do bamCompare (using SES) on A and C. Will it then make sense to compare the two comparisons (A-B & A-C)?

If such normalization isn't okay, what are the best tools to normalize ATAC-Seq datasets with different sequencing depths so that one can perform comparisons like above? Thanks for any suggestions or comments.

• Yes, that's another good way of approaching things. bigwigCompare does assume that the input bigWigs are scaled appropriately and the procedure you suggest will create a nicely robust comparison. – Devon Ryan Oct 7 '19 at 15:56