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Computational Modeling of Physiological Systems: Constructing the angiome: a global angiogenesis protein interaction network

机译:生理系统的计算模型:构建血管瘤:全球性血管生成蛋白相互作用网络

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摘要

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.
机译:血管生成是由先前存在的微血管形成的新血管。血管生成过度和不足与许多疾病有关,包括癌症,与年龄有关的黄斑变性,缺血性心脏病,脑病和骨骼肌疾病。需要对血管生成调节过程有一个全面的了解,以改善对这些疾病的治疗。为了鉴定与血管生成有关的蛋白质,我们为各种高通量数据来源开发了一种新颖的整合框架。名为GeneHits的系统用于扩展已知的血管生成途径,以构建血管生成蛋白(一种用于血管生成的蛋白质-蛋白质相互作用网络)。该网络由478个蛋白质和1488个相互作用组成。通过交叉验证和对来自体外血管生成测定的五个基因表达数据集的分析来验证该网络。我们计算了血管瘤的拓扑特性。我们分析了血管生成注释和相关蛋白的功能富集。我们还构建了具有1,233种蛋白质和5,726种相互作用的扩展血管瘤,以得出血管生成中蛋白质-蛋白质相互作用的更完整图谱。最后,扩展的血管瘤被用于鉴定驱动血管生成和抗血管生成信号网络的生长因子信号网络。该分析的结果可用于鉴定不同疾病条件下的基因和蛋白质以及治疗干预的假定靶点,作为实验验证的高级候选对象。

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