I would like to compare two conditions with each two ChIP-seq (H3K27me3) samples. I searched for tools for differential binding and found that many including diffbind and csaw compares two conditions with read counts from pull down library only, not using input/control library/read count. The csaw has a step to use input/control but it is essentially for filtering regions not using it for statistical test for differential binding. I don't understand why these tools do not consider input/control read count. If input/control is different between two conditions, this should be considered for differential binding. Could you explain the rationale behind the algorithms or idea about this ?

Thanks for your answer. It is much clearer now to me. By the way, in the website you mentioned, I cannot read math notation in the wrapping up remarks probably due to browser formatting. Can you check it?

The mathematical notation in the report doesn't render properly because it's not recognised by Github. The solution is easy - just clone the repository and compile the report with

`rmarkdown::render("subtract_control.Rmd")`

. Then you get to see the results of the simulations as well.