A hypergeometric test was used to test for overrepresentation of each DNA motif in the set of differentially accessible peaks compared to a background set of peaks. We tested motifs present in the JASPAR database65 for human (species code 9606) by first identifying which peaks contained each motif using the motifmatchr R package (https://bioconductor.org/packages/motifmatchr). We computed the GC content (percentage of G and C nucleotides) for each differentially accessible peak and sampled a background set of 40,000 peaks such that the background set was matched for overall GC content, accessibility and peak width. This was performed using the FindMotifs function in Signac, with features.match = c(‘GC.percent’, ‘count’, ‘sequence.length’).
