Extracting multi-way chromatin contacts from Hi-C data.

There is a growing realization that multi-way chromatin contacts formed in chromosome structures are fundamental units of gene regulation. However, due to the paucity and complexity of such contacts, it is challenging to detect and identify them using experiments. Based on an assumption that chromos...

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Main Authors: Lei Liu, Bokai Zhang, Changbong Hyeon
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-12-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009669&type=printable
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author Lei Liu
Bokai Zhang
Bokai Zhang
Changbong Hyeon
author_facet Lei Liu
Bokai Zhang
Bokai Zhang
Changbong Hyeon
author_sort Lei Liu
collection DOAJ
description There is a growing realization that multi-way chromatin contacts formed in chromosome structures are fundamental units of gene regulation. However, due to the paucity and complexity of such contacts, it is challenging to detect and identify them using experiments. Based on an assumption that chromosome structures can be mapped onto a network of Gaussian polymer, here we derive analytic expressions for n-body contact probabilities (n > 2) among chromatin loci based on pairwise genomic contact frequencies available in Hi-C, and show that multi-way contact probability maps can in principle be extracted from Hi-C. The three-body (triplet) contact probabilities, calculated from our theory, are in good correlation with those from measurements including Tri-C, MC-4C and SPRITE. Maps of multi-way chromatin contacts calculated from our analytic expressions can not only complement experimental measurements, but also can offer better understanding of the related issues, such as cell-line dependent assemblies of multiple genes and enhancers to chromatin hubs, competition between long-range and short-range multi-way contacts, and condensates of multiple CTCF anchors.
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spelling doaj.art-9b196c29bc444ae6af0a7ffd6ad0d2082025-03-03T05:31:25ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-12-011712e100966910.1371/journal.pcbi.1009669Extracting multi-way chromatin contacts from Hi-C data.Lei LiuBokai ZhangBokai ZhangChangbong HyeonThere is a growing realization that multi-way chromatin contacts formed in chromosome structures are fundamental units of gene regulation. However, due to the paucity and complexity of such contacts, it is challenging to detect and identify them using experiments. Based on an assumption that chromosome structures can be mapped onto a network of Gaussian polymer, here we derive analytic expressions for n-body contact probabilities (n > 2) among chromatin loci based on pairwise genomic contact frequencies available in Hi-C, and show that multi-way contact probability maps can in principle be extracted from Hi-C. The three-body (triplet) contact probabilities, calculated from our theory, are in good correlation with those from measurements including Tri-C, MC-4C and SPRITE. Maps of multi-way chromatin contacts calculated from our analytic expressions can not only complement experimental measurements, but also can offer better understanding of the related issues, such as cell-line dependent assemblies of multiple genes and enhancers to chromatin hubs, competition between long-range and short-range multi-way contacts, and condensates of multiple CTCF anchors.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009669&type=printable
spellingShingle Lei Liu
Bokai Zhang
Bokai Zhang
Changbong Hyeon
Extracting multi-way chromatin contacts from Hi-C data.
PLoS Computational Biology
title Extracting multi-way chromatin contacts from Hi-C data.
title_full Extracting multi-way chromatin contacts from Hi-C data.
title_fullStr Extracting multi-way chromatin contacts from Hi-C data.
title_full_unstemmed Extracting multi-way chromatin contacts from Hi-C data.
title_short Extracting multi-way chromatin contacts from Hi-C data.
title_sort extracting multi way chromatin contacts from hi c data
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009669&type=printable
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AT bokaizhang extractingmultiwaychromatincontactsfromhicdata
AT changbonghyeon extractingmultiwaychromatincontactsfromhicdata