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 method of controllability implementation used identifies protein sets of interest through changes to classification between the HIN and VIN. Unfortunately, robust classification methods do not detect a change between the two networks in this study. As it is a measure of the robustness of the network to structural changes in the absence of each protein, this suggests that the HIN upholds its typical control structure during IAV infection. This could be a consequence of the interaction data used or it may be that the strategy applied here cannot distinguish between the behavior of healthy and diseased states. Knowing the extent of changes to cell behavior within immune response pathways [50] [51] [52] , apoptosis signaling [53, 54] , and transcriptional processes [55] [56] [57] during infection, the IAV infected cell can be interpreted as a different system. The failure to see this distinction may be a shortcoming of the robust controllability calculation, especially knowing that the 11 robust proteins are not unique due to the method's use of a single MIS.