Inferring Functional Epigenetic Modules by Integrative Analysis of Multiple Heterogeneous Networks

Abstract

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Gene expression and methylation are critical biological processes for cells, and how to integrate these heterogeneous data has been extensively investigated, which is the foundation for revealing the underlying patterns of cancers. The vast majority of the current algorithms fuse gene methylation and expression into a network, failing to fully explore the relations and heterogeneity of them. To resolve these problems, in this study we define the epigenetic modules as a gene set whose members are co-methylated and co-expressed. To address the heterogeneity of data, we construct gene co-expression and co-methylation networks, respectively. In this case, the epigenetic module is characterized as a common module in multiple networks. Then, a non-negative matrix factorization-based algorithm that jointly clusters the co-expression and co-methylation networks is proposed for discovering the epigenetic modules (called Ep-jNMF). Ep-jNMF is more accurate than the baselines on the artificial data. Moreover, Ep-jNMF identifies more biologically meaningful modules. And the modules can predict the subtypes of cancers. These results indicate that Ep-jNMF is efficient for the integration of expression and methylation data.

Keywords

• DNA methylation
• network biology
• functional epigenetic module
• non-negative matrix factorization
• heterogeneous network