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Int. J. Mol. Sci. 2016, 17(2), 216; doi:10.3390/ijms17020216

Temporal Genetic Modifications after Controlled Cortical Impact—Understanding Traumatic Brain Injury through a Systematic Network Approach

College of Mechanical and Electronic Engineering, Fujian Agriculture and Forestry University, Fujian 350002, China
Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan
Institute of Biomedical Science, National Chung Hsing University, Taichung 402, Taiwan
Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan
Institution Review Board (IRB), Christian Mennonite Hospital, Hualien 970, Taiwan
Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung City 833, Taiwan
Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei 110, Taiwan
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Xiaofeng Jia
Received: 21 October 2015 / Revised: 30 November 2015 / Accepted: 10 December 2015 / Published: 6 February 2016
(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)
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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. View Full-Text
Keywords: brain injury; network biomarker; systems biology; protein–protein interaction; drug target; cell cycle brain injury; network biomarker; systems biology; protein–protein interaction; drug target; cell cycle

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wong, Y.-H.; Wu, C.-C.; Wu, J.C.-C.; Lai, H.-Y.; Chen, K.-Y.; Jheng, B.-R.; Chen, M.-C.; Chang, T.-H.; Chen, B.-S. Temporal Genetic Modifications after Controlled Cortical Impact—Understanding Traumatic Brain Injury through a Systematic Network Approach. Int. J. Mol. Sci. 2016, 17, 216.

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