title: Establishment of quantitative severity evaluation model for spinal cord injury by metabolomic fingerprinting.
abstract: Spinal cord injury (SCI) is a devastating event with a limited hope for recovery and represents an enormous public health issue. It is crucial to understand the disturbances in the metabolic network after SCI to identify injury mechanisms and opportunities for treatment intervention. Through plasma 1H-nuclear magnetic resonance (NMR) screening, we identified 15 metabolites that made up an "Eigen-metabolome" capable of distinguishing rats with severe SCI from healthy control rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We also found that 16 metabolites regulated by 130 enzymes in the metabolic network impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a linear discrimination model to cluster rats with severe and mild SCI and control rats into separate groups and identify the interactive relationships between metabolic biomarkers in the global metabolic network. We identified 10 clusters in the global metabolic network and defined them as distinct metabolic disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid, arachidonic acid metabolism; NAD-NADPH conversion process, tyrosine metabolism, and cadaverine and putrescine metabolism were included. In summary, we presented a novel interdisciplinary method that integrates metabolomics and global metabolic network analysis to visualize metabolic network disturbances after SCI. Our study demonstrated the systems biological study paradigm that integration of 1H-NMR, metabolomics, and global metabolic network analysis is useful to visualize complex metabolic disturbances after severe SCI. Furthermore, our findings may provide a new quantitative injury severity evaluation model for clinical use.
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Surgery, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Peng
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Trauma Surgery, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Trauma Surgery, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Computational Mathematics and Biostatistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Surgery, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Mitchell Jay
authors.initials: MJ
authors.lastname: Cohen
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Trauma Surgery, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Sun
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Charles Damien
authors.initials: CD
authors.lastname: Lu
authors.affiliation: Program for Computational Biology, Systems Biology, and Translational Research, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Trauma Surgery, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Department of Computational Mathematics and Biostatistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Disaster and Emergency Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000175:diagnosis* / Q000378:metabolism*
references.citation: Glia. 2010 Jul;58(9):1133-44
references.pmid: 20468054
references.citation: Horm Metab Res. 1995 Jun;27(6):287-92
references.pmid: 7557841
references.citation: J Neurochem. 1999 Aug;73(2):684-92
references.pmid: 10428065
references.citation: Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E3-10
references.pmid: 21045171
references.citation: Biochim Biophys Acta. 2009 Mar;1794(3):476-85
references.pmid: 19150419
references.citation: Nature. 1994 May 19;369(6477):233-5
references.pmid: 7514272
references.citation: J Steroid Biochem Mol Biol. 1995 Oct;55(1):85-92
references.pmid: 7577724
references.citation: J Biol Chem. 2011 Jul 8;286(27):23631-5
references.pmid: 21566142
references.citation: Spine (Phila Pa 1976). 2001 Dec 15;26(24 Suppl):S2-12
references.pmid: 11805601
references.citation: J Neurosci Res. 1997 Sep 15;49(6):681-97
references.pmid: 9335256
references.citation: Chin Med J (Engl). 2010 Sep;123(17):2315-9
references.pmid: 21034541
references.citation: Spinal Cord. 2008 May;46(5):344-51
references.pmid: 18026171
references.citation: J Proteome Res. 2011 Jan 7;10(1):277-87
references.pmid: 21105667
references.citation: Am J Pathol. 1996 Jul;149(1):21-8
references.pmid: 8686745
references.citation: Arch Phys Med Rehabil. 1983 Mar;64(3):107-10
references.pmid: 6338859
references.citation: PM R. 2010 Mar;2(3):202-8; quiz 228
references.pmid: 20359685
references.citation: Muscle Nerve. 2009 Oct;40(4):499-519
references.pmid: 19705475
references.citation: J Appl Physiol (1985). 2011 May;110(5):1204-10
references.pmid: 21393466
references.citation: J Biol Chem. 2003 Sep 5;278(36):33972-7
references.pmid: 12821649
references.citation: J Mol Biol. 2002 Jul 19;320(4):751-70
references.pmid: 12095253
references.citation: J Biol Chem. 2002 Jul 19;277(29):25851-4
references.pmid: 12011102
references.citation: Am J Phys Med Rehabil. 1998 Mar-Apr;77(2):108-12
references.pmid: 9558010
references.citation: PLoS One. 2012;7(8):e43152
references.pmid: 22912814
references.citation: J Biol Chem. 2002 Jul 19;277(29):25847-50
references.pmid: 12011103
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7659-63
references.pmid: 9636206
references.citation: Neurosci Lett. 1999 Apr 2;264(1-3):153-6
references.pmid: 10320037
references.citation: Neurochem Res. 2013 May;38(5):895-905
references.pmid: 23462880
references.citation: J Biol Chem. 1996 Nov 1;271(44):27237-40
references.pmid: 8910295
references.citation: Am J Phys Med Rehabil. 2008 Sep;87(9):758-67
references.pmid: 18716488
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4003-8
references.pmid: 15020765
references.citation: Spinal Cord. 2002 Mar;40(3):110-7
references.pmid: 11859437
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11853-8
references.pmid: 8876227
references.citation: Paraplegia. 1992 Jun;30(6):401-9
references.pmid: 1635789