Fig. 2

Component-specific pathways and epigenetic regulation. a Expression heatmap of the component-specific pathways (P value < 0.05, Fisher’s exact test). For each pathway, the mean expression profile of the associated deregulated genes was calculated. Samples were ordered by the ratio of rescaled E-score and S-score. b Lateral bars correspond to each pathway and to the proportion of genes whose expression levels were correlated with the DNA methylation level (DM, differentially methylated). c Heatmap of the correlations between DNA methylation and gene expression with the E-score and S-score for known oncogenes and tumor suppressor genes (FDR adjusted P value < 0.05, Pearson’s correlation test). The circle size is proportional to the correlation coefficient value. d Correlation plots between the DNA methylation level and the CDH3 (epithelial marker) and FBN1 (mesenchymal marker) gene expression levels; color gradient changes correspond to the E-score or S-score. For each plot, the correlation coefficient and P value are shown (Pearson’s correlation test). e, f The network displays miRNAs whose expression levels are negatively correlated with the E-score (e) or S-score (f) and their targeted pathways (among the component-specific pathways between E-comp and S-comp) based on validated miRNA-target associations. The network was restricted to miRNAs that were negatively correlated with the expression of their target (FDR adjusted P value < 0.05, Pearson’s correlation test) and targeted at least 2 (e) out of 5 (f) different component-specific pathways. The edge thickness is proportional to the number of genes in the pathway targeted by the miRNA. The circle size of each pathway is proportional to the number of genes targeted by the miRNA in the network. miRNAs that have been described in the MPM literature are represented by a gray square, and undescribed miRNAs are represented by a black square