Fig. 1.

A schematic example of the PPI network-based synergy score calculation. The calculation strategy in this example was from the method described in [28]. The green and red triangles represent two different drugs. Each drug is targeting on certain protein targets denoted as circles with the same color as the corresponding drug. All the targets are mapped into a disease-specific PPI network, in which purple circles are pathological proteins, while white circles are other high-related proteins, and different proteins are connected by PPIs. Based on the disease-specific PPI network (G), topology score TS(A, B) can be calculated by the topology connection and centrality for targets of drug A (TA) and targets of drug B (TB), where IP means a integrative topological parameter calculated by integrating betweenness, closeness and a variant of the eigenvector PageRank through PCA, IP _A (i) is calculated for the target i of drug A and IP _B (i) for the target j of drug B, and min(d _i,j ) represents the minimum shortest path from the ith target of drug A to all targets of drug B. Another agent score (AS), in which P _i,j represents the similarity score between the ith phenotype of drug A and the jth phenotype of drug B, can also be coupled with to adjust the topology-based score. At last, a synergy score can be calculated by the product of TS and AS