title: Global quantitative modeling of chromatin factor interactions.
abstract: 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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America; Graduate Program in Quantitative and Computational Biology, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America; Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskaya
mesh_terms: D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D002843:Chromatin / Q000737:chemistry*; D019295:Computational Biology; D004331:Drosophila melanogaster; D019277:Entropy; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry; D015233:Models, Statistical; D016011:Normal Distribution; D011336:Probability; D015203:Reproducibility of Results; D049490:Systems Biology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors