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Emergence of co-expression in gene regulatory networks

Yin, Wencheng, Mendoza, Luis, Monzon Sandoval, Jimena, Urrutia, Araxi O. and Gutierrez, Humberto 2022. Emergence of co-expression in gene regulatory networks. PLoS ONE 16 (4) , e0247671. 10.1371/journal.pone.0247671

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Transcriptomes are known to organize themselves into gene co-expression clusters or modules where groups of genes display distinct patterns of coordinated or synchronous expression across independent biological samples. The functional significance of these co-expression clusters is suggested by the fact that highly coexpressed groups of genes tend to be enriched in genes involved in common functions and biological processes. While gene co-expression is widely assumed to reflect close regulatory proximity, the validity of this assumption remains unclear. Here we use a simple synthetic gene regulatory network (GRN) model and contrast the resulting co-expression structure produced by these networks with their known regulatory architecture and with the co-expression structure measured in available human expression data. Using randomization tests, we found that the levels of co-expression observed in simulated expression data were, just as with empirical data, significantly higher than expected by chance. When examining the source of correlated expression, we found that individual regulators, both in simulated and experimental data, fail, on average, to display correlated expression with their immediate targets. However, highly correlated gene pairs tend to share at least one common regulator, while most gene pairs sharing common regulators do not necessarily display correlated expression. Our results demonstrate that widespread co-expression naturally emerges in regulatory networks, and that it is a reliable and direct indicator of active co-regulation in a given cellular context.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This is an open access article distributed under the terms of the Creative Commons Attribution License
Publisher: Public Library of Science
ISSN: 1932-6203
Date of First Compliant Deposit: 13 May 2022
Date of Acceptance: 22 March 2021
Last Modified: 15 May 2023 12:51

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