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 total, a controllability analysis identifies the key components of a system that must be manipulated to drive desired system outcomes [35] . An example PPI network in Fig. 1a is transformed into its state space matrix representation. With the inclusion of two independent inputs (u 1 and u 2 ), the controllability matrix is full rank. Therefore, the system is fully controllable and it is possible to drive the protein concentrations to any desired state. Applying the idea of controllability to a cell at the onset of viral infection, a virus aims to control cellular functions (the system of proteins), promote virus replication tasks, and reach a final infected cell state. While it would be advantageous to interpret the infection from this control perspective, mathematical limits due to large system dimensions prevent the direct application of traditional controllability methods to PPI networks.