Blacklist regions account for a significant portion of ChIP-seq reads, are driven by artifacts in genome assemblies, and removal of these regions is essential to removing noise in genomics assays. (a) The number of blacklisted regions across species with their average size, genomic coverage, and input datasets excluding assembly gaps used for hg38, mm10, dm6, and ce11 respectively. (b) An UpSet plot displaying the breakdown of uniquely annotated regions in hg19 and hg38, and the shared regions between them. Low-mappability (Low-Map.) regions account for the majority of unique regions in both hg19 and hg38. (c) Applying the blacklist to ChIP-seq peaks results in an overall reduced correlation and, in the highlighted example, results in a more biologically meaningful interpretation of the data.