Network controllers and proteins with high protein page rank are enriched with viral targets.

In (A) we determined indispensable, neutral and dispensable proteins in the underlying protein interaction network. Randomizing such sets 10,000 times, we observed that proteins that are indispensable for the control of the underlying network preferably occurred in an increasing number of pathways. In turn, we found the opposite for dispensable proteins. (B) Randomizing sets of proteins that are targeted by Hepatitis, Herpes, HIV, Influenza and other viruses 10,000 times, we observed that indispensable proteins are preferably targeted by viruses (P<10−4) while the opposite held for dispensable nodes. (C) Randomizing the set of top PageRank proteins, we determined their enrichment in sets of indispensable, neutral and dispensable proteins. We observed that indispensable and neutral nodes significantly accumulated top PageRank proteins. In the inset, we observed that proteins in an increasing number of pathways were enriched with top PageRank proteins. (D) Randomizing sets of targets of Hepatitis, Herpes, HIV, Influenza and other viruses 10,000 times we observed that proteins with highest protein PageRank were significantly targeted (P<10−4).