Detection of changes in deoxyribonucleic acid (DNA)-protein interactions from ChIP-seq data is a crucial step in unraveling the regulatory networks behind biological processes. The simplest variation of this problem is the differential peak calling (DPC) problem. Here, one has to find genomic regions with ChIP-seq signal changes between two cellular conditions in the interaction of a protein with DNA. The great majority of peak calling methods can only analyze one ChIP-seq signal at a time and are unable to perform DPC. Recently, a few approaches based on the combination of these peak callers with statistical tests for detecting differential digital expression have been proposed. However, these methods fail to detect detailed changes of protein-DNA interactions.