Spectral identification of topological domains.

Abstract

Topological domains have been proposed as the backbone of interphase chromosome structure. They are regions of high local contact frequency separated by sharp boundaries. Genes within a domain often have correlated transcription. In this paper, we present a computational efficient spectral algorithm to identify topological domains from chromosome conformation data (Hi-C data). We consider the genome as a weighted graph with vertices defined by loci on a chromosome and the edge weights given by interaction frequency between two loci. Laplacian-based graph segmentation is then applied iteratively to obtain the domains at the given compactness level. Comparison with algorithms in the literature shows the advantage of the proposed strategy. An efficient algorithm is presented to identify topological domains from the Hi-C matrix. The Matlab source code and illustrative examples are available at http://bionetworks.ccmb.med.umich.edu/ : indikar@med.umich.edu Supplementary data are available at Bioinformatics online.