title: Temporal Genetic Modifications after Controlled Cortical Impact--Understanding Traumatic Brain Injury through a Systematic Network Approach.
abstract: Traumatic brain injury (TBI) is a primary injury caused by external physical force and also a secondary injury caused by biological processes such as metabolic, cellular, and other molecular events that eventually lead to brain cell death, tissue and nerve damage, and atrophy. It is a common disease process (as opposed to an event) that causes disabilities and high death rates. In order to treat all the repercussions of this injury, treatment becomes increasingly complex and difficult throughout the evolution of a TBI. Using high-throughput microarray data, we developed a systems biology approach to explore potential molecular mechanisms at four time points post-TBI (4, 8, 24, and 72 h), using a controlled cortical impact (CCI) model. We identified 27, 50, 48, and 59 significant proteins as network biomarkers at these four time points, respectively. We present their network structures to illustrate the protein-protein interactions (PPIs). We also identified UBC (Ubiquitin C), SUMO1, CDKN1A (cyclindependent kinase inhibitor 1A), and MYC as the core network biomarkers at the four time points, respectively. Using the functional analytical tool MetaCore™, we explored regulatory mechanisms and biological processes and conducted a statistical analysis of the four networks. The analytical results support some recent findings regarding TBI and provide additional guidance and directions for future research.
authors: College of Mechanical and Electronic Engineering, Fujian Agriculture and Forestry University, Fujian 350002, China. syslab.yvonwong@gmail.com.|Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan. syslab.yvonwong@gmail.com.|Institute of Biomedical Science, National Chung Hsing University, Taichung 402, Taiwan. syslab.yvonwong@gmail.com.
authors: Yung-Hao
authors: YH
authors: Wong
authors: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan. d9761820@oz.nthu.edu.tw.
authors: Chia-Chou
authors: CC
authors: Wu
authors: Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan. dr.jcwu@gmail.com.
authors: John Chung-Che
authors: JC
authors: Wu
authors: Institution Review Board (IRB), Christian Mennonite Hospital, Hualien 970, Taiwan. hsienyonglei@gmail.com.
authors: Hsien-Yong
authors: HY
authors: Lai
authors: Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. kychen08@tmu.edu.tw.
authors: Kai-Yun
authors: KY
authors: Chen
authors: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan. jbrpo810716@gmail.com.
authors: Bo-Ren
authors: BR
authors: Jheng
authors: Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung City 833, Taiwan. chenmien@ms76.hinet.net.
authors: Mien-Cheng
authors: MC
authors: Chen
authors: Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei 110, Taiwan. kevinchang@tmu.edu.tw.
authors: Tzu-Hao
authors: TH
authors: Chang
authors: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan. bschen@ee.nthu.edu.tw.
authors: Bor-Sen
authors: BS
authors: Chen
mesh_terms: D000465:Algorithms; D000818:Animals; D015415:Biomarkers; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D019295:Computational Biology / Q000379:methods; D008954:Models, Biological; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D015203:Reproducibility of Results; D015398:Signal Transduction; D020521:Stroke / Q000378:metabolism; D049490:Systems Biology / Q000379:methods; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: brain injury; cell cycle; drug target; network biomarker; protein–protein interaction; systems biology