Fig. 5

Functional PPI networks. The differentially methylated modules consist of a network of genes based on their functional connectivity using PPI. Each module has a primary gene that is connected to other target genes in the network. Each module was significant p < 0.05 using the Functional Epigenetic Module method. GraphNEL networks were exported from the modified FEM R package to Cytoscape (version 3.8) using RCy3 and further annotated. Node colour represents methylation state; blue nodes show hypermethylation, with yellow representing hypomethylation. A different colour of the node border refers to differential expression; those with red borders are upregulated, those with green are downregulated. Edge widths are proportional to the average statistic of the PPI network. (A) The bmpr1aa/smad3b/smad4a module is associated with BMP and TGFβ signalling pathways and was reported to be significant through three different seed genes. (B) The tfpd2/cdk6 module is associated with cell cycle regulation, identified twice with individual seed genes.