GenomeDISCO

GenomeDISCO is a software tool designed to assess the similarity of contact maps obtained from chromosome conformation capture experiments. The three-dimensional organization of chromatin plays a critical role in gene regulation and disease. High-throughput chromosome conformation capture experiments like Hi-C are used to obtain genome-wide maps of three-dimensional chromatin contacts. However, it is challenging to robustly estimate data quality and systematically compare contact maps due to the multi-scale, hierarchical structure of chromatin contacts and the resulting properties of experimental noise in the data. Measuring concordance of contact maps is important for assessing the reproducibility of replicate experiments and for modeling variation between different cellular contexts.

GenomeDISCO introduces a concordance measure called DIfferences between Smoothed COntact maps that smooths contact maps using random walks on the contact map graph to estimate concordance. The key idea is to reduce noise in contact maps before estimating concordance. The software tool is tested on simulated datasets to benchmark its sensitivity to different types of noise that affect chromatin contact maps. The results show that GenomeDISCO can distinguish biological replicates from samples obtained from different cell types accurately. Moreover, it can generalize to other chromosome conformation capture assays, such as HiChIP.