Constructing the angiome: a global angiogenesis protein interaction network

Angiogenesis is the formation of new blood vessels from pre-existing microvessels. Excessive and insufficient angiogenesis have been associated with many diseases including cancer, age-related macular degeneration, ischemic heart, brain, and skeletal muscle diseases. A comprehensive understanding of angiogenesis regulatory processes is needed to improve treatment of these diseases. To identify proteins related to angiogenesis, we developed a novel integrative framework for diverse sources of high-throughput data. The system, called GeneHits, was used to expand on known angiogenesis pathways to construct the angiome, a protein-protein interaction network for angiogenesis. The network consists of 478 proteins and 1,488 interactions. The network was validated through cross validation and analysis of five gene expression datasets from in vitro angiogenesis assays. We calculated the topological properties of the angiome. We analyzed the functional enrichment of angiogenesis-annotated and associated proteins. We also constructed an extended angiome with 1,233 proteins and 5,726 interactions to derive a more complete map of protein-protein interactions in angiogenesis. Finally, the extended angiome was used to identify growth factor signaling networks that drive angiogenesis and antiangiogenic signaling networks. The results of this analysis can be used to identify genes and proteins in different disease conditions and putative targets for therapeutic interventions as high-ranked candidates for experimental validation.