Global quantitative modeling of chromatin factor interactions.
Chromatin is the driver of gene regulation, yet understanding the molecular interactions underlying chromatin factor combinatorial patterns (or the "chromatin codes") remains a fundamental challenge in chromatin biology. Here we developed a global modeling framework that leverages chromati...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1003525&type=printable |
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| _version_ | 1850023820755206144 |
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| author | Jian Zhou Olga G Troyanskaya |
| author_facet | Jian Zhou Olga G Troyanskaya |
| author_sort | Jian Zhou |
| collection | DOAJ |
| description | Chromatin is the driver of gene regulation, yet understanding the molecular interactions underlying chromatin factor combinatorial patterns (or the "chromatin codes") remains a fundamental challenge in chromatin biology. Here we developed a global modeling framework that leverages chromatin profiling data to produce a systems-level view of the macromolecular complex of chromatin. Our model ultilizes maximum entropy modeling with regularization-based structure learning to statistically dissect dependencies between chromatin factors and produce an accurate probability distribution of chromatin code. Our unsupervised quantitative model, trained on genome-wide chromatin profiles of 73 histone marks and chromatin proteins from modENCODE, enabled making various data-driven inferences about chromatin profiles and interactions. We provided a highly accurate predictor of chromatin factor pairwise interactions validated by known experimental evidence, and for the first time enabled higher-order interaction prediction. Our predictions can thus help guide future experimental studies. The model can also serve as an inference engine for predicting unknown chromatin profiles--we demonstrated that with this approach we can leverage data from well-characterized cell types to help understand less-studied cell type or conditions. |
| format | Article |
| id | doaj-art-d0c830252ec74a52b34e1c597f47fecd |
| institution | DOAJ |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2014-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-d0c830252ec74a52b34e1c597f47fecd2025-08-20T03:01:15ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582014-03-01103e100352510.1371/journal.pcbi.1003525Global quantitative modeling of chromatin factor interactions.Jian ZhouOlga G TroyanskayaChromatin is the driver of gene regulation, yet understanding the molecular interactions underlying chromatin factor combinatorial patterns (or the "chromatin codes") remains a fundamental challenge in chromatin biology. Here we developed a global modeling framework that leverages chromatin profiling data to produce a systems-level view of the macromolecular complex of chromatin. Our model ultilizes maximum entropy modeling with regularization-based structure learning to statistically dissect dependencies between chromatin factors and produce an accurate probability distribution of chromatin code. Our unsupervised quantitative model, trained on genome-wide chromatin profiles of 73 histone marks and chromatin proteins from modENCODE, enabled making various data-driven inferences about chromatin profiles and interactions. We provided a highly accurate predictor of chromatin factor pairwise interactions validated by known experimental evidence, and for the first time enabled higher-order interaction prediction. Our predictions can thus help guide future experimental studies. The model can also serve as an inference engine for predicting unknown chromatin profiles--we demonstrated that with this approach we can leverage data from well-characterized cell types to help understand less-studied cell type or conditions.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1003525&type=printable |
| spellingShingle | Jian Zhou Olga G Troyanskaya Global quantitative modeling of chromatin factor interactions. PLoS Computational Biology |
| title | Global quantitative modeling of chromatin factor interactions. |
| title_full | Global quantitative modeling of chromatin factor interactions. |
| title_fullStr | Global quantitative modeling of chromatin factor interactions. |
| title_full_unstemmed | Global quantitative modeling of chromatin factor interactions. |
| title_short | Global quantitative modeling of chromatin factor interactions. |
| title_sort | global quantitative modeling of chromatin factor interactions |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1003525&type=printable |
| work_keys_str_mv | AT jianzhou globalquantitativemodelingofchromatinfactorinteractions AT olgagtroyanskaya globalquantitativemodelingofchromatinfactorinteractions |