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.

In robust controllability (by Liu et al. [38] , pictured in Fig. 1b) , the MIS is re-calculated (size N D ′) after removing each node from the network. The node is then classified by its effect on the manipulation required to control the network, where an increase in the size of the MIS makes it more difficult to control the network and a decrease in the size of the MIS makes it easier to control the network. The removal of: an indispensable node increases the number of driver nodes (N D ′ > N D ), a dispensable node decreases the number of driver nodes (N D ′ < N D ), and a neutral node has no effect on the number of driver nodes (N D ′ = N D ). This method has previously been applied to many network types such as gene regulatory networks, food webs, citation networks, and PPI networks to better understand what drives the dynamics of each system [29, 38] . While it is useful to observe the structural changes to the network after the removal of singular nodes, this method only considers one possible MIS. A second global controllability method by Jia et al. [39] (Pictured in Fig. 1c ) classifies a node by its role across all possible MISs. A critical node is included in all possible MISs, an intermittent node is included in some possible MISs, and a redundant node is not included in any possible MISs. This method places each node in the broader context of all possible control configurations.