How to deal with low-depth ChIP-seq / ATAC-seq samples

Question

[Vanilla]

Hi all!

I got several ATAC-seq and ChIP-seq samples, but unfortunately, some of them are with low sequencing depth after I trimmed the reads with mapping quality, duplicates, and mitochondrial DNA and keep proper paired (it's paired end reads). Only a few peaks can be called for them and it's hard to get any informative indication from such peaks.

I'm wondering:

1. whether or not I can merge some replicates to a single sample for downstream analysis (peak calling, annotation, etc). If so, what's the proper way to merge them? Should I merge the raw reads from sequencer, or merge the reads got from each sample after trimming? Any additional normalization should be taken into consideration?

2. what kind of normalization can I do to call ChIP-seq peaks without a control? How can I compare two results, one got with control but the other without?

Thanks for anyone with any hints!

Best, Vanilla