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.

Overall, global calculations identify a set of proteins for consideration that are more important within the VIN than the HIN. This is demonstrated through a comparison of degree and betweenness for the identified robust and global driver sets in Fig. 5 . Proteins identified in the robust analysis show little deviation in both degree (Fig. 5a) and betweenness (Fig. 5b) measures after the addition of virus-host interactions to the network. In contrast, proteins identified in the global analysis show much larger deviations in degree (Fig. 5a) and betweenness ( Fig. 5b) with all proteins having a betweenness of 0 in the HIN with an up to two log unit increase in the VIN (Table 4 ). Because the identified proteins were not responsible for information flow until the addition of virus-host interactions to the network, this suggests that the global protein set may identify key regulators of host immune response to infection.