I processed my ChIP-seq and ATAC samples using the ENCODE pipeline (https://github.com/ENCODE-DCC/chip-seq-pipeline2 and https://github.com/ENCODE-DCC/atac-seq-pipeline). These pipelines gives outputs such as aligned bam files, bigwig files for signal normalized to control, and IDR filtered big bed peak files.
When my samples are not normalized, they have an efficiency difference so that some samples overall have higher peaks than others. The ENCODE pipeline corrects this problem by correcting to controls, but to my knowledge that output is a bigwig file. I am concerned that if I look at differential peaks using the bam files to look for enrichment, then many peaks will be lost due to the efficiency difference. On the other hand, I can't seem to find any programs where I can use a bigwig file and a peak file to calculate differential peaks.
Does anyone have any good strategies for calculating differential peaks from the normalized outputs of the ENCODE pipeline?