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.

We developed an analysis to test if IAV is selectively targeting host proteins based on controllability characteristics. 10,000 random sets of 752 proteins (the number of IAV interacting proteins) were pulled from the host proteins of the VIN. Their robust type distributions were plotted against the classification results of IAV interacting proteins, driver proteins, and all proteins in the VIN (Fig. 3a-c) . The randomly sampled sets closely resemble all proteins of the network, not the true interacting protein set, suggesting that robust controllability behavior of interacting proteins is not a coincidence of network construction (one-sided p = 0.51, 0.49, and 0.50 for indispensable, neutral, and dispensable, respectively). IAV interacting proteins tend to be indispensable compared to the percentage of all proteins that are indispensable (Fig. 3a) . This suggests that viruses prefer to interact with proteins that are vital to cellular control. Driver proteins are very likely to be dispensable proteins compared to the percent of all proteins that are dispensable (Fig. 3c) . Further, the mean and median log degree and betweenness of the randomly sampled protein sets is significantly lower than the same measurements of the true IAV interacting set (p < 2.2 × 10 − 16 , 2.2 × 10 − 16 , Fig. 4 ), signifying that virus interacting proteins are in positions of network significance. Overall, the robust controllability results of IAV interacting proteins suggest that the virus may be selectively targeting host proteins based on controllability characteristics.