HiC-DC+ enables systematic 3D interaction calls and differential analysis for Hi-C and HiChIP

Merve Sahin, Wilfred Wong, Yingqian Zhan, Kinsey Van Deynze, Richard Koche, Christina S. Leslie
2021 Nature Communications  
AbstractRecent genome-wide chromosome conformation capture assays such as Hi-C and HiChIP have vastly expanded the resolution and throughput with which we can study 3D genomic architecture and function. Here, we present HiC-DC+, a software tool for Hi-C/HiChIP interaction calling and differential analysis using an efficient implementation of the HiC-DC statistical framework. HiC-DC+ integrates with popular preprocessing and visualization tools and includes topologically associating domain (TAD)
more » ... and A/B compartment callers. We found that HiC-DC+ can more accurately identify enhancer-promoter interactions in H3K27ac HiChIP, as validated by CRISPRi-FlowFISH experiments, compared to existing methods. Differential HiC-DC+ analyses of published HiChIP and Hi-C data sets in settings of cellular differentiation and cohesin perturbation systematically and quantitatively recovers biological findings, including enhancer hubs, TAD aggregation, and the relationship between promoter-enhancer loop dynamics and gene expression changes. HiC-DC+ therefore provides a principled statistical analysis tool to empower genome-wide studies of 3D chromatin architecture and function.
doi:10.1038/s41467-021-23749-x pmid:34099725 pmcid:PMC8184932 fatcat:luifzry3kbc6nnd6q64wn747ei