A dual controllability analysis of influenza virus-host protein-protein interaction networks for antiviral drug target discovery

Ackerman, Emily E.; Alcorn, John F.; Hase, Takeshi; Shoemaker, Jason E.

The directed PPI network from Vinayagam et al. [40] was restricted to confident interactions (see Methods for a b c Fig. 1 a An example protein-protein interaction network with three proteins and two protein translation process inputs. The state space representation of the same network demonstrates that the change in state of a protein's concentration is a function of its current state and an input process. A classic controllability analysis demonstrates that this system is fully controllable and could, therefore, be driven to any possible state change in every protein. b Example application of robust controllability, which determines the robustness of the network after the removal of a protein. c Example application of global controllability which assesses the importance of a protein to all methods of network control network construction details), creating a network containing 6281 proteins and 31,079 interactions. This network is referred to as the "Host Interaction Network" (HIN). Influenza A virus-host interactions from Watanabe et al. [41] were narrowed to 2592 directed interactions between 11 influenza A virus (IAV) proteins (HA, M1, M2, NA, NP, NS1, NS2, PA, PB1, PB2, and PB1-F2 proteins) and 752 "IAV interacting proteins" preexisting in the HIN. After integration into the HIN, the network contains 6292 proteins and 33,671 interactions. This network is referred to as the "Virus Integrated Network" (VIN).