cCRES - Cell type agnostic Classification

Many uses of cCREs are based on the regulatory role associated with their biochemical signatures. Thus, ENCODE putatively defined cCREs in one of the following annotation groups based on each element’s dominant biochemical signals across all available biosamples. Analogous to GENCODE's catalog of genes, which are defined irrespective of their varying expression levels and alternative transcripts across different cell types, we provide a general, cell type-agnostic classification of cCREs based on the max-Zs as well as its proximity to the nearest annotated TSS:

• cCREs with promoter-like signatures (cCRE-PLS) fall within 200 bp (center to center) of an annotated GENCODE TSS and have high DNase and H3K4me3 signals (evaluated as DNase and H3K4me3 max-Z scores, defined as the maximal DNase or H3K4me3 Z scores across all biosamples with data; see Methods).

• cCREs with enhancer-like signatures (cCRE-ELS) have high DNase and H3K27ac max-Z scores and must additionally have a low H3K4me3 max-Z score if they are within 200 bp of an annotated TSS. The subset of cCREs-ELS within 2 kb of a TSS is denoted proximal (cCRE-pELS), while the remaining subset is denoted distal (cCRE-dELS).

• DNase-H3K4me3 cCREs have high H3K4me3 max-Z scores but low H3K27ac max-Z scores and do not fall within 200 bp of a TSS.

• CTCF-only cCREs have high DNase and CTCF max-Z scores and low H3K4me3 and H3K27ac max-Z scores.