Loopsim: enrichment analysis of chromosome conformation capture with fast empirical distribution simulation

Gene regulation is intricately influenced by the three-dimensional organization of the genome. In particular, chromatin can exist in loop structures that enable long-range regulatory interactions. By utilizing chromosome conformation capture techniques such as Hi-C, valuable information regarding the organization of these loop structures in 3D space can be obtained. Although functional/feature enrichment is now a common downstream analysis for various genomic platforms to provide biological context, tools specifically designed for high-throughput assays that capture chromosome conformation remain relatively limited. Here, we present Loopsim, a command-line application that performs enrichment analysis on Hi-C loop profiles against user-defined regions (available on GitHub at https://github.com/CutaneousBioinf/Loopsim). Loopsim efficiently simulates a background distribution using a distinctive sampling approach that considers loop size, intervals, loop–loop distances, and structure; it then computes statistics based on the empirical null distribution.