GenomeDISCO: a concordance score for chromosome conformation capture experiments using random walks on contact map graphs

The three-dimensional organization of chromatin plays a critical role in gene regulation and disease. High-throughput chromosome conformation capture experiments such as Hi-C are used to obtain genome-wide maps of 3D chromatin contacts. However, robust estimation of data quality and systematic comparison of these contact maps is challenging due to the multi-scale, hierarchical structure of the data and the resulting idiosyncratic properties of experimental noise. We introduce a multi-scale concordance measure called GenomeDISCO (DIfferences between Smoothed COntact maps) for assessing the similarity of a pair of contact maps obtained from chromosome capture experiments. We denoise the contact maps using random walks on the contact map graph, and integrate concordance at multiple scales of smoothing. We use simulated datasets to benchmark GenomeDISCO's sensitivity to different types of noise typically affecting chromatin contact maps. When applied to a large collection of Hi-C datasets, GenomeDISCO accurately distinguishes biological replicates from samples obtained from different cell types. Software implementing GenomeDISCO is available at http://github.com/kundajelab/genomedisco.