title: Molecular Architecture of Spinal Cord Injury Protein Interaction Network.
abstract: Spinal cord injury (SCI) is associated with complex pathophysiological processes that follow the primary traumatic event and determine the extent of secondary damage and functional recovery. Numerous reports have used global and hypothesis-driven approaches to identify protein changes that contribute to the overall pathology of SCI in an effort to identify potential therapeutic interventions. In this study, we use a semi-automatic annotation approach to detect terms referring to genes or proteins dysregulated in the SCI literature and develop a curated SCI interactome. Network analysis of the SCI interactome revealed the presence of a rich-club organization corresponding to a "powerhouse" of highly interacting hub-proteins. Studying the modular organization of the network have shown that rich-club proteins cluster into modules that are specifically enriched for biological processes that fall under the categories of cell death, inflammation, injury recognition and systems development. Pathway analysis of the interactome and the rich-club revealed high similarity indicating the role of the rich-club proteins as hubs of the most prominent pathways in disease pathophysiology and illustrating the centrality of pro-and anti-survival signal competition in the pathology of SCI. In addition, evaluation of centrality measures of single nodes within the rich-club have revealed that neuronal growth factor (NGF), caspase 3, and H-Ras are the most central nodes and potentially an interesting targets for therapy. Our integrative approach uncovers the molecular architecture of SCI interactome, and provide an essential resource for evaluating significant therapeutic candidates.
authors.affiliation: Neuroscience Institute, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, United States of America; Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors.forename: Ali
authors.initials: A
authors.lastname: Alawieh
authors.affiliation: Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sabra
authors.affiliation: Neuroscience Institute, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, United States of America; Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors.forename: Zahraa
authors.initials: Z
authors.lastname: Sabra
authors.affiliation: Neuroscience Institute, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, United States of America; Department of Microbiology and Immunology, Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425, United States of America; Ralph H. Johnson Veteran Affairs Medical Center, Charleston, SC 29425, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tomlinson
authors.affiliation: Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.
authors.forename: Fadi A
authors.initials: FA
authors.lastname: Zaraket
mesh_terms: D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D060066:Protein Interaction Maps; D020543:Proteome; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D020543:Proteome