Fig. 8

Multi-dimensional patterns of differential expression in cancer. a Box plots of the fraction of differentially expressed genes in cancer, which remain differentially expressed when specific cancer subsets are compared to normal-adjacent samples, for six different TCGA cancer types (LSCC, LUAD, KIRC, KIRP, BLCA and COAD), and for four different scenarios: genes overexpressed in cancer and considering cancers with neutral or copy-number loss of that gene (first panel), genes underexpressed in cancer and considering cancers with neutral or copy-number gain (second panel), genes overexpressed in cancer and considering cancers with the highest levels of gene promoter DNAm (third panel), and finally genes underexpressed in cancer and considering cancers with the lowest levels of gene promoter DNAm (fourth panel). In each panel, blue denotes the fraction of over/underexpressed genes that are differentially expressed when only the specific cancer subset is compared to the normal samples. Magenta denotes the fraction that are overexpressed and green denotes the fraction that are underexpressed. b Scatterplots of mRNA expression against either copy-number variation level (CNV) or DNAm level for selected genes in LSCC. The selected genes represent examples of genes from a. For instance, BIRC5 in LSCC is overexpressed in cancer compared to normal, and this overexpression relative to normal is independent of the CNV of the cancer. c As b, but the 3D scatterplots also display the CNV or DNAm level. These plots illustrate that the difference in expression between cancer and normal is also independent of the other variable (e.g. CNV or DNAm). For instance, the underexpression of GPX3 in LSCC is neither driven by promoter DNAm nor by CNV losses. BLCA bladder adenocarcinoma, C cancerous, CN copy number, CNV copy-number variation, DEG differentially expressed gene, COAD colon adenocarcinoma, DNAm DNA methylation, KIRC kidney renal cell carcinoma, KIRP kidney papillary carcinoma, LSCC lung squamous cell carcinoma, LUAD lung adenocarcinoma, mRNA messenger RNA, N normal, Overexpr. overexpression, Underexr. underexpression