Revealing cancer driver genes through integrative transcriptomic and epigenomic analyses with Moonlight
Fig 2
Integration of Moonlight and EpiMix for prediction of cancer driver genes.
(A) Number of differentially methylated CpGs as found from EpiMix in oncogenic mediators predicted from Moonlight’s primary layer. The differentially methylated CpGs are categorized into methylation status and stratified by cancer (sub)type. (B) Heatmap showing number of differentially methylated CpGs and classifications of methylation status in the oncogenic mediators in basal-like breast cancer. The heatmap was generated using the plotGMA function. (C) Venn diagram comparing oncogenic mediators predicted from Moonlight’s primary layer with functional genes predicted from EpiMix in basal-like breast cancer. The functional genes are genes containing differentially methylated CpG pairs whose DNA methylation state is associated with expression of the gene. Only those functional genes that contained the same methylation state in all of its associated CpGs were included in this comparison, and moreover, the dual methylation states were excluded. (D) Heatmap showing the effect of the predicted driver genes in basal-like breast cancer on apoptosis and proliferation of cells. This heatmap was generated using the function plotMoonlightMet. These effects define the basis upon which the oncogenic mediators are predicted from the PRA step in Moonlight’s primary layer. (E) Comparison between the predicted driver genes with the predicted oncogenic mediators in all three cancer (sub)types where the driver genes were predicted with the new functionality GMA in Moonlight’s secondary layer, and the oncogenic mediators were predicted with Moonlight’s primary layer. The comparisons were quantified in terms of overlaps with genes reported in the COSMIC Cancer Gene Census (CGC) by computing the precision and sensitivity. The precision was calculated as (TP/(TP + FP))*100 and sensitivity as (TP/(TP + FN))*100. The true positives (TP) are the overlap between the gene set (either the driver genes or the oncogenic mediators) and the CGC. The false positives (FP) are those genes found in the gene set but are not included in CGC. The false negatives (FN) comprise those genes reported in CGC but are not predicted in our gene set.