Loopsim: Enrichment Analysis ofChromosomeConformation Capture with Fast EmpiricalDistribution Simulation

The three-dimensional organization of the genome intricately influences the regulation of genes.In particular, chromatin can exist as loop structures that enable long-range regulatory interactions. By utilizingchromosome conformation capture techniques such as Hi-C, valuable information regarding the organizationof these loop structures in 3D space can be obtained. While gene-set enrichment has become a standard down-stream analysis for different genomic data to provide biological context, tools that providefunctionalenrich-ment for high throughput assays capturing chromosome conformation are relatively limited. Here, we presentLoopsim, a command-line application that performs enrichment analysis on Hi-C loop profiles against user-defined regions. Loopsim efficiently simulates a background distribution using a distinctive sampling approachthat considers loop size, intervals, loop-loop distances, and structure;itthencomputes statistics based on theempirical null distribution. Overall design: To evaluate Loopsim's performance, we used a Hi-C loop profile generated by deep sequencing Hi-C libraries (~1 billion reads/reaction). Then, using a contact map combining resolutions (resolution in this case meaning the length of the interval of loop ends) of 5Kb and 10Kb, we identified Hi-C loops in each library using Mustache.