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

TitleAn integrated model for detecting significant chromatin interactions from high-resolution Hi-C data.
Publication TypeJournal Article
Year of Publication2017
AuthorsCarty M, Zamparo L, Sahin M, González A, Pelossof R, Elemento O, Leslie CS
JournalNat Commun
Date Published2017 05 17
KeywordsAnimals, Binding Sites, Cell Line, Tumor, Chromatin, Chromosome Mapping, Chromosomes, Human, Pair 6, Computational Biology, CpG Islands, Datasets as Topic, Genome, Genomics, Histone Code, Humans, Mice, Models, Genetic, Promoter Regions, Genetic, Software

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 (<500 kb) and longer (>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.

Alternate JournalNat Commun
PubMed ID28513628
PubMed Central IDPMC5442359
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
U01 HG007893 / HG / NHGRI NIH HHS / United States
U01 HG009395 / HG / NHGRI NIH HHS / United States