Figure 2.

Selection of protein candidates for pharmaceutical synergy. The selection of source proteins that are potential candidates for pharmaceutical synergy is based on topological properties, favoring the in-between nodes with respect to hubs. Hubs proteins are highly connected nodes that tend to be more essential than non-hub proteins but targeting them might produce a large number of side effects. The drug combination strategy consists of targeting less important proteins to have less impact on the overall system alone while maintaining drug efficacy thanks to the synergistic effect on several points of the biological network. These secondary proteins correspond to in-between nodes in the network. They are identified using bridging centrality index that is computed as the product of its betweenness centrality and a bridging coefficient that evaluates if a node is located between high degree nodes (Table 1).