Fig. 5

Epigenetic model for the tumor phenotype and its validation. a Genes that are in a box with red ribbon correspond to genes having an associated Super-enhancer. Yellow flash corresponds to genetic alterations. b Diagram is shown of the design for validating the model through inhibition of MET by siRNA to test the potential conversion of a basal to classical cellular phenotype. c PCA based on the differentially expressed genes from RNA-seq on basal siMET and basal control (scramble siRNA) samples. Basal samples were used as active individuals in the PCA construction, whereas the pure classical sample was projected on the two first dimensions. d GSEA plot is shown for GATA6 targets with vertical black lines corresponding to GATA6 putative targets ordered by their statistical tests of the differential analysis between siMET vs. control in basal samples. The curve illustrates the running enrichment score for the gene set ranked by the difference between the cohorts, showing global upregulation of GATA6 targets in the siMET condition. e GSEA plot for cell cycle is shown with vertical black lines corresponding to cell cycle genes (mitotic cell cycle, Reactome) ordered by their statistical tests of the differential analysis comparing siMET vs. control in basal samples. Green curve represents the running enrichment score for this gene set across the ranked list, which demonstrates global downregulation of those genes in the siMET condition