IC-Finder: Inferring robustly the hierarchical organization of chromatin folding

Abstract

The spatial organization of the genome plays a crucial role in the regulation of gene expression. Recent experimental techniques like Hi-C have emphasized the segmentation of genomes into interaction compartments that constitute conserved functional domains participating in the maintenance of a proper cell identity. Here, we propose a novel method, ICFinder, to identify interaction compartments (IC) from experimental Hi-C maps. IC-Finder is based on a hierarchical clustering approach that we adapted to account for the polymeric nature of chromatin. Based on a benchmark of realistic in silico Hi-C maps, we show that IC-Finder is one of the best methods in terms of reliability and is the most efficient numerically. IC-Finder proposes two original options: A probabilistic description of the inferred compartments and the possibility to explore the various hierarchies of chromatin organization. Applying the method to experimental data in fly and human, we show how the predicted segmentation may depend on the normalization scheme and how 3D compartmentalization is tightly associated with epigenomic information. IC-Finder provides a robust and generic 'all-in-one' tool to uncover the general principles of 3D chromatin folding and their influence on gene regulation.