An integrated model for detecting significant chromatin interactions from high-resolution Hi-C data

Mark Carty, Lee Zamparo, Merve Sahin, Alvaro González, Raphael Pelossof, Olivier Elemento and Christina S. Leslie ()
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Mark Carty: Computational Biology Program, Memorial Sloan Kettering Cancer Center
Lee Zamparo: Computational Biology Program, Memorial Sloan Kettering Cancer Center
Merve Sahin: Computational Biology Program, Memorial Sloan Kettering Cancer Center
Alvaro González: Computational Biology Program, Memorial Sloan Kettering Cancer Center
Raphael Pelossof: Computational Biology Program, Memorial Sloan Kettering Cancer Center
Olivier Elemento: Institute for Computational Biomedicine, Weill Cornell Medical College
Christina S. Leslie: Computational Biology Program, Memorial Sloan Kettering Cancer Center

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Here we present HiC-DC, a principled method to estimate the statistical significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC uses hurdle negative binomial regression account for systematic sources of variation in Hi-C read counts—for example, distance-dependent random polymer ligation and GC content and mappability bias—and model zero inflation and overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell line, HiC-DC detects significant interactions at the sub-topologically associating domain level, identifying potential structural and regulatory interactions supported by CTCF binding sites, DNase accessibility, and/or active histone marks. CTCF-associated interactions are most strongly enriched in the middle genomic distance range (∼700 kb–1.5 Mb), while interactions involving actively marked DNase accessible elements are enriched both at short ( 1.5 Mb) genomic distances. There is a striking enrichment of longer-range interactions connecting replication-dependent histone genes on chromosome 6, potentially representing the chromatin architecture at the histone locus body.

Date: 2017
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DOI: 10.1038/ncomms15454

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