DiffHiChIP: Identifying differential chromatin contacts from HiChIP data

This repository contains the source code and data related to the manuscript: Sourya Bhattacharyya, Daniela Salgado Figueroa et al., DiffHiChIP: Identifying differential chromatin contacts from HiChIP data AbstractChromatin conformation capture (3C) assays such as HiChIP are widely used to study interactions between cis-regulatory and structural elements. However, robust methods for detecting condition-specific loops remain limited. We introduce DiffHiChIP, the first comprehensive framework to call differential loops from HiChIP and similar 3C protocols. DiffHiChIP supports DESeq2 and edgeR using either complete contact map or a subset of contacts for background estimation, incorporates edgeR with generalized linear model (GLM) using either quasi-likelihood F-test or likelihood ratio test, and implements independent hypothesis weighting (IHW) as well as a distance stratification technique for modeling distance decay of contacts in estimating statistical significance. Our results on 5 datasets suggest that edgeR GLM-based models with IHW correction reliably capture differential interactions, including long-range, that are supported by published Hi-C data and reference studies. As HiChIP data become increasingly used for modeling chromatin regulation, DiffHiChIP promises to have a broad impact and utility.