Integrative construction of regulatory region networks in 127 human reference epigenomes by matrix factorization

© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. Despite large experimental and computational efforts aiming to dissect the mechanisms underlying disease risk, mapping cis-regulatory elements to target genes remains a challenge. Here, we introduce a mat...

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Bibliographic Details
Main Authors: Liu, Dianbo, Davila-Velderrain, Jose, Zhang, Zhizhuo, Kellis, Manolis
Other Authors: Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Format: Article
Language:English
Published: Oxford University Press (OUP) 2021
Online Access:https://hdl.handle.net/1721.1/134786
Description
Summary:© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. Despite large experimental and computational efforts aiming to dissect the mechanisms underlying disease risk, mapping cis-regulatory elements to target genes remains a challenge. Here, we introduce a matrix factorization framework to integrate physical and functional interaction data of genomic segments. The framework was used to predict a regulatory network of chromatin interaction edges linking more than 20 000 promoters and 1.8 million enhancers across 127 human reference epigenomes, including edges that are present in any of the input datasets. Our network integrates functional evidence of correlated activity patterns from epigenomic data and physical evidence of chromatin interactions. An important contribution of this work is the representation of heterogeneous data with different qualities as networks. We show that the unbiased integration of independent data sources suggestive of regulatory interactions produces meaningful associations supported by existing functional and physical evidence, correlating with expected independent biological features.