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

Nature Communications
Mark CartyChristina S Leslie

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 (<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.

References

May 4, 2010·Nature·Zhijun DuanWilliam S Noble
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Mar 1, 2012·Nature Methods·Jason Ernst, Manolis Kellis
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Citations

Feb 3, 2018·Nucleic Acids Research·Enrique VidalGuillaume J Filion
Jul 20, 2018·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Dejun LinWilliam S Noble
Mar 21, 2019·Genome Biology·Galip Gürkan YardımcıWilliam S Noble
Jan 16, 2020·Genome Biology·Christopher Jf CameronMathieu Blanchette
Sep 19, 2019·Nature Communications·Sourya BhattacharyyaFerhat Ay
Feb 6, 2021·Statistical Applications in Genetics and Molecular Biology·Qi ZhangYutong Lai
Mar 21, 2021·Epigenetics & Chromatin·Beoung Hun Lee, Suhn K Rhie
Mar 20, 2021·Scientific Reports·Artem V LuzhinOmar L Kantidze
Apr 24, 2021·Molecular Cell·Yuri PritykinChristina S Leslie
May 7, 2021·Nature Reviews. Molecular Cell Biology·Ivana Jerkovic, Giacomo Cavalli
Jun 9, 2021·Nature Communications·Merve SahinChristina S Leslie
May 18, 2021·Computational and Structural Biotechnology Journal·Haiyan GongXiaotong Zhang
Oct 14, 2020·Developmental Cell·Benjamin R Sabari
Dec 16, 2021·Nucleic Acids Research·Darren TaylorMiguel R Branco

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Datasets Mentioned

BETA
GM12878
GSM892307

Methods Mentioned

BETA
proximity ligation
Hi-C
ICE
ChIP-seq
PCR
in

Software Mentioned

aln
DC R package
Hi
DC
Segway
GRanges
ChromHMM
HiC
- C
HiCNorm

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