Inference of epigenetic subnetworks by Bayesian regression with the incorporation of prior information

Abstract

Changes in gene expression have been thought to play a crucial role in various types of cancer. With the advance of high-throughput experimental techniques, many genome-wide studies are underway to analyze underlying mechanisms that may drive the changes in gene expression. It has been observed that the change could arise from altered DNA methylation. However, the knowledge about the degree to which epigenetic changes might cause differences in gene expression in cancer is currently lacking. By considering the change of gene expression as the response of altered DNA methylation, we introduce a novel analytical framework to identify epigenetic subnetworks in which the methylation status of a set of highly correlated genes is predictive of a set of gene expression. By detecting highly correlated modules as representatives of the regulatory scenario underling the gene expression and DNA methylation, the dependency between DNA methylation and gene expression is explored by a Bayesian regression model with the incorporation of g-prior followed by a strategy of an optimal predictor subset selection. The subsequent network analysis indicates that the detected epigenetic subnetworks are highly biologically relevant and contain many verified epigenetic causal mechanisms. Moreover, a survival analysis indicates that they might be effective prognostic factors associated with patient survival time.