comb-p is a command-line tool and a python library that manipulates BED files of possibly irregularly spaced P-values and (1) calculates auto-correlation, (2) combines adjacent P-values, (3) performs false discovery adjustment, (4) finds regions of enrichment (i.e. series of adjacent low P-values) and (5) assigns significance to those regions. In addition, tools are provided for visualization and assessment. We provide validation and example uses on bisulfite-seq with P-values from Fishers exact test, tiled methylation probes using a linear model and Dam-ID for chromatin binding using moderated t-statistics. Because the library accepts input in a simple, standardized format and is unaffected by the origin of the P-values, it can be used for a wide variety of applications.