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 and Christina S. Leslie ()
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Merve Sahin: Memorial Sloan Kettering Cancer Center
Wilfred Wong: Memorial Sloan Kettering Cancer Center
Yingqian Zhan: Memorial Sloan Kettering Cancer Center
Kinsey Van Deynze: University of California at San Diego
Richard Koche: Memorial Sloan Kettering Cancer Center
Christina S. Leslie: Memorial Sloan Kettering Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Recent 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) 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.

Date: 2021
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DOI: 10.1038/s41467-021-23749-x

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