Altering Indispensable Proteins in Controlling Directed Human Protein Interaction Network.

The numerous interconnections within complex systems enable us to control networks towards a desired state through a few suitable selected nodes, which are called driver nodes. Recent works analyzed directed human Protein-Protein Interaction (PPI) network based on structural control theory. They found that indispensable proteins, whose removal increase the number of driver nodes, are the primary targets of human viruses and drugs. However, the human PPI network is usually incomplete and may include many false-positive or false-negative interactions. That prompts us to ask whether these indispensable proteins are stable to possible structural changes. Here, we present a method to alter the type of indispensable proteins and thereby investigate the stability of indispensable proteins. By comparing the sets of indispensable proteins before and after structural changes to the network, we find that very few added or removed interactions can change the type of many indispensable nodes. Furthermore, some indispensable proteins are very sensitive to structural changes and have significantly lower interactions than the other indispensable proteins. The results indicate that indispensable proteins are sensitive to structural changes. Therefore, approaches based on structural control theory should be used with caution because of the incomplete nature of these networks.