The 100 top scoring gene sets show numerous instances of three biological processes: NFκB signaling, EMT (epithelial-mesenchymal transition), and hypoxia/glycolysis. Indeed, 62 out of the 100 top scoring sets account for 27 NFkB, 25 EMT and 10 hypoxia/glycolysis annotations (Figure 2). The strong presence of EMT and NFκB signatures in association with necrosis agrees with the observations made in the original GBM study. However, an additional group of 8 biological themes (shown inside a red box in Figure 2) only appear below rank 97 in the ranked results list and are thus eclipsed. For example, the original study noted deregulation of the p53 pathway as an underlying relevant biological theme of GBM. Our analysis finds significant enrichment of 15 gene sets corresponding to the p53 pathway. However, the first such gene set appears only at rank 114 and thus, despite being statistically significant, would more likely be overlooked in a routine interpretation of the GSEA results.
