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Table 2 Betti number analysis and its implication for multiple protein targeting. The data for the 5-year survival was again derived from Surveillance, Epidemiology and End Results Database (SEER), the nominal Betti number was calculated using JPLEX, and represents the Betti number for the full cancer network, and the Best Betti represents the lowest Betti number achieved by removal of a protein from the specific cancer protein-protein interaction (PPI) network. Through sequential removal of protein pairs across the entire PPI network of each cancer, we were able to identify combinations of protein pairs exhibiting most effect on the PPI network. Shown are the node combinations which produce the most reduction in network complexity as measured by the “Best Betti, double node elimination”, each paired node elimination results in equivalent drop in Betti, e.g. HRAS-FLT3 and HRAS-NRAS both have Best Betti of 83 in AML

From: Design principles for cancer therapy guided by changes in complexity of protein-protein interaction networks

   AML Bladder CML Colorectal Endometrial Glioma NSCL Pancreatic Renal SCL Thyroid
5 years Survival [%] 23.6 78.1 55.2 63.6 68.6 33.4 18 5.5 69.5 6.2 97.2
Nominal Betti 107 20 114 51 45 128 50 38 51 149 24
Best Betti [single node elimination] 95 15 101 41 35 109 37 29 34 131 17
Best Betti [double node elimination] 83 11 88 31 26 90 29 21 26 113 10
Paired node elimination   HRAS – MAPK3         ITGA2 – ITGA3  
  ARAF – MAPK3         ITGA2 – ITGA6  
  RAF1 – MAPK3         ITGA3 – ITGA6  
HRAS – FLT3 NRAS – MAPK3         ITGA2 – ITGA2B  
HRAS – NRAS HRAS – MAPK1 AKT1 – AKT2 AKT1 – AKT2   NRAS – HRAS     ITGA3 – ITGA2B HRAS – NRAS
FLT3 – NRAS ARAK – MAPK1 AKT1 – AKT3 AKT1 – AKT3 ILK – PDPK1 NRAS – KRAS EGFR – KRAS NFKB1 – KRAS HIF1A – GAB1 ITGA6 – ITGA2B HRAS – KRAS
HRAS – KRAS RAF1 – MAPK1 AKT2 – AKT3 AKT2 – AKT3   HRAS – KRAS ERBB2 – KRAS RELA – KRAS GAB1 – EPAS1 ITGA2 – ITGB1 NRAS – KRAS
FLT3 – KRAS NRAS – MAPK1         ITGA3 – ITGB1  
NRAS – KRAS MAPK3 – KRAS         ITGA6 – ITGB1  
  MAPK1 – KRAS         ITGA2B – ITGB1  
  MAPK3 – BRAF         ITGA2 – ITGAV  
  MAPK1 - BRAF         ITGA3 - ITGAV