m(6)A-Driver: Identifying Context-Specific mRNA m(6)A Methylation-Driven Gene Interaction Networks



Zhang, Song-Yao, Zhang, Shao-Wu, Liu, Lian, Meng, Jia ORCID: 0000-0003-3455-205X and Huang, Yufei
(2016) m(6)A-Driver: Identifying Context-Specific mRNA m(6)A Methylation-Driven Gene Interaction Networks. PLOS COMPUTATIONAL BIOLOGY, 12 (12). e1005287-.

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Abstract

As the most prevalent mammalian mRNA epigenetic modification, N6-methyladenosine (m6A) has been shown to possess important post-transcriptional regulatory functions. However, the regulatory mechanisms and functional circuits of m6A are still largely elusive. To help unveil the regulatory circuitry mediated by mRNA m6A methylation, we develop here m6A-Driver, an algorithm for predicting m6A-driven genes and associated networks, whose functional interactions are likely to be actively modulated by m6A methylation under a specific condition. Specifically, m6A-Driver integrates the PPI network and the predicted differential m6A methylation sites from methylated RNA immunoprecipitation sequencing (MeRIP-Seq) data using a Random Walk with Restart (RWR) algorithm and then builds a consensus m6A-driven network of m6A-driven genes. To evaluate the performance, we applied m6A-Driver to build the context-specific m6A-driven networks for 4 known m6A (de)methylases, i.e., FTO, METTL3, METTL14 and WTAP. Our results suggest that m6A-Driver can robustly and efficiently identify m6A-driven genes that are functionally more enriched and associated with higher degree of differential expression than differential m6A methylated genes. Pathway analysis of the constructed context-specific m6A-driven gene networks further revealed the regulatory circuitry underlying the dynamic interplays between the methyltransferases and demethylase at the epitranscriptomic layer of gene regulation.

Item Type: Article
Uncontrolled Keywords: RNA, Adenosine, Sequence Analysis, RNA, DNA Methylation, Algorithms, Models, Genetic, Computer Simulation, Gene Regulatory Networks
Depositing User: Symplectic Admin
Date Deposited: 20 Feb 2019 10:46
Last Modified: 19 Jan 2023 01:02
DOI: 10.1371/journal.pcbi.1005287
Open Access URL: https://doi.org/10.1371/journal.pcbi.1005287
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3033141