CT-FOCS: a novel method for inferring cell type-specific enhancer-promoter maps

Abstract

Spatiotemporal gene expression patterns are governed to a large extent by enhancer elements, typically located distally from their target genes. Identification of enhancer-promoter (EP) links that are specific and functional in individual cell types is a key challenge in understanding gene regulation. We introduce CT-FOCS, a new statistical inference method that utilizes multiple replicates per cell type to infer cell type-specific EP links. Computationally predicted EP links are usually benchmarked against experimentally determined chromatin interactions measured by ChIA-PET and promoter-capture HiC techniques. We expand this validation scheme by using also loops that overlap in their anchor sites. In analyzing 1,366 samples from ENCODE, Roadmap epigenomics and FANTOM5, CT-FOCS inferred highly cell type-specific EP links more accurately than state-of-the-art methods. We illustrate how our inferred EP links drive cell type-specific gene expression and regulation.