Recent sequencing technologies enable joint quantification of promoters and their enhancer regions, allowing inference of enhancer–promoter links. We show that current enhancer–promoter inference methods produce a high rate of false positive links. We introduce FOCS, a new inference method, and by benchmarking against ChIAPET, HiChIP, and eQTL data show that it results in lower false discovery rates and at the same time higher inference power. | Hait et al. Genome Biology 2018 19 56 https s13059-018-1432-2 METHOD Open Access FOCS a novel method for analyzing enhancer and gene activity patterns infers an extensive enhancer promoter map Tom Aharon Hait1 3 David Amar1 2 Ron Shamir1 and Ran Elkon3 4 Abstract Recent sequencing technologies enable joint quantification of promoters and their enhancer regions allowing inference of enhancer promoter links. We show that current enhancer promoter inference methods produce a high rate of false positive links. We introduce FOCS a new inference method and by benchmarking against ChIA- PET HiChIP and eQTL data show that it results in lower false discovery rates and at the same time higher inference power. By applying FOCS to 2630 samples taken from ENCODE Roadmap Epigenomics FANTOM5 and a new compendium of GRO-seq samples we provide extensive enhancer promotor maps http focs . We illustrate the usability of our maps for deriving biological hypotheses. Keywords Enhancers Promoters Gene regulation ENCODE Roadmap FANTOM5 GRO-seq eRNA ChIA-PET eQTL Background putative regulatory elements in the genome 2 . As EN- Deciphering the regulatory role of the noncoding part of CODE analyses were mainly applied to cancer cell lines the human genome is a major challenge. With the com- a follow-up project the Roadmap Epigenomics applied pletion of the sequencing of the genome efforts have similar analyses to a large collection of human primary shifted over the past decade towards understanding the cells and tissues in order to establish more physiological epigenome. These efforts aim at understanding regula- maps of common and cell type-specific putative regula- tory mechanisms outside the protein-coding sequences tory elements 3 . Given the plethora of candidate en- that allow the production of thousands of different cell hancer regions called by these projects the next types from the same DNA blueprint. Enhancer elements pressing challenge is to .
