Connecting signaling and metabolic pathways in EGF receptor-mediated oncogenesis of glioblastoma
Fig 3
Development of a GBM-specific significant network from HPPIN.
(A) A human protein-protein interactome network (HPPIN) was established based on experimentally validated interactome data of STRING database (left panel: the total network where nodes and edges are marked in grey). The SMIN was extracted from the HPPIN as signaling-metabolic interconnected path-dependent network between fourteen signaling and six groups of metabolic pathways as indicated in Fig 2 (highlighted as orange nodes and blue edges within the HPPIN on the left panel). The interconnections in the SMIN between one signaling (CSNK2A1) and one metabolic (NDUFA13) pathway protein through PPIs were highlighted on the right panel.(B) A GBM-specific network (left panel with yellow nodes and green edges) was developed from the SMIN (orange nodes and blue edges within the total background network) considering interconnecting paths with at least one differentially expressed protein identified from comparative proteome analysis of U87MG (EGFRwt) and U87MGvIII (EGFRvIII) GBM. The interconnecting paths between the same signaling (CSNK2A1) and metabolic (NDUFA13) pathway protein after exclusion of non-GBM specific interconnections are shown on the right panel. (C) The GBM-specific network based on significant nodes (z ≥1) and significant interconnected paths (path score ≥80% of the highest path score of each SM pair) identified from the weighted network were indicated with blue nodes and red edges within the GBM-specific network with yellow node and green edge. The interconnecting paths in the GBM-specific significant network between CSNK2A1 and NDUFA13 are shown as examples on the right panel.