Viral Perturbations of Host Networks Reflect Disease Etiology
A,C, The neighborhoods of viral targets in the host interactome, along with their disease associations, represent “viral disease networks”. Diseases associated with genes in the neighborhood of EBV (A) or HPV16 (C) targets that are not yet characterized with viral implications are shown as grey nodes. Node size is proportional to the degree of a node (number of neighbors it has) in the viral disease network. B,D, Diseases associated with genes in the neighborhoods of randomly generated viral targets of EBV (B) or HPV16 (D) are significantly sparser than the neighborhoods of actual viral targets. E, Benchmarking the prioritization using relative risk with virally infected patients showed that the higher-ranked diseases in the prioritization are more often associated with viral infection. F, Differentially expressed genes in E6 or E7 induced IMR90 and HFK cell populations with their associated diseases. If a gene is regulated by a specific viral protein target, it is also almost always differentially expressed in the cell population where that specific viral protein is induced. For example, EDN1 is regulated by FOS, an E7 target, and EDN1 is differentially expressed in E7 induced cell populations. Large grey nodes: diseases with high relative risk among HPV patients.