title: A Rich-Club Organization in Brain Ischemia Protein Interaction Network.
abstract: Ischemic stroke involves multiple pathophysiological mechanisms with complex interactions. Efforts to decipher those mechanisms and understand the evolution of cerebral injury is key for developing successful interventions. In an innovative approach, we use literature mining, natural language processing and systems biology tools to construct, annotate and curate a brain ischemia interactome. The curated interactome includes proteins that are deregulated after cerebral ischemia in human and experimental stroke. Network analysis of the interactome revealed a rich-club organization indicating the presence of a densely interconnected hub structure of prominent contributors to disease pathogenesis. Functional annotation of the interactome uncovered prominent pathways and highlighted the critical role of the complement and coagulation cascade in the initiation and amplification of injury starting by activation of the rich-club. We performed an in-silico screen for putative interventions that have pleiotropic effects on rich-club components and we identified estrogen as a prominent candidate. Our findings show that complex network analysis of disease related interactomes may lead to a better understanding of pathogenic mechanisms and provide cost-effective and mechanism-based discovery of candidate therapeutics.
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.|Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors: Ali
authors: A
authors: Alawieh
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425.|Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors: Zahraa
authors: Z
authors: Sabra
authors: Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors: Mohammed
authors: M
authors: Sabra
authors: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425.
authors: Stephen
authors: S
authors: Tomlinson
authors: Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors: Fadi A
authors: FA
authors: Zaraket
mesh_terms: D000465:Algorithms; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D016000:Cluster Analysis; D066289:Data Curation; D004967:Estrogens / Q000627:therapeutic use; D006801:Humans; D058977:Molecular Sequence Annotation; D060066:Protein Interaction Maps; D015398:Signal Transduction; D020521:Stroke / Q000150:complications / Q000188:drug therapy
chemical_list: D004967:Estrogens