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.

Controllability analyses confirm that IAV interacting proteins are in positions of significance for both types of classification. The increased population of indispensable IAV interacting proteins (robust controllability: N D ′ > N D , Fig. 3a ) compared to what would be expected by random chance suggests that it would be more difficult for an outside influence (such as viral infection) to control the network after removing the IAV interacting proteins opposed to a randomly selected protein. This is logical as IAV interacting proteins act as the connection between viral proteins and the host network where control is initiated. The increased population of redundant IAV interacting proteins (global controllability: never a driver protein, Fig. 3f ) when compared to the random expectation indicates that more IAV interacting proteins are always being manipulated internally than would be expected by chance. This means that they are fully incorporated into the control structure of the VIN. From these two results, one can conclude that IAV interacting proteins contribute to both the "gate" (the ease of entering the system) and the "heart" (the proteins responsible for propagating control through the system) of the network control structure during infection. These findings support the idea that viruses are likely to interact with a b Fig. 6 Percent of each a) robust classification type and b) global classification type confirmed in 6 siRNA screens (Brass, Karlas, Shapira, Hao, Konig, Watanabe). None of the 6 possible classifications are more than 5% validated in the screenings, suggesting that experimental findings do not favor certain protein controllability types proteins which offer an advantage to total network control.