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Unformatted text preview: Subscriber access provided by TEXAS A&M UNIV COLL STATION Journal of Proteome Research is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Article Application of Proteomics in the Discovery of Candidate Protein Biomarkers in a Diabetes Autoantibody Standardization Program Sample Subset Thomas O. Metz, Wei-Jun Qian, Jon M. Jacobs, Marina A. Gritsenko, Ronald J. Moore, Ashoka D. Polpitiya, Matthew E. Monroe, David G. Camp II, Patricia W. Mueller, and Richard D. Smith J. Proteome Res. , 2008 , 7 (2), 698-707 DOI: 10.1021/pr700606w Publication Date (Web): 20 December 2007 Downloaded from http://pubs.acs.org on November 20, 2008 More About This Article Additional resources and features associated with this article are available within the HTML version: Supporting Information Links to the 1 articles that cite this article, as of the time of this article download Access to high resolution figures Links to articles and content related to this article Copyright permission to reproduce figures and/or text from this article Application of Proteomics in the Discovery of Candidate Protein Biomarkers in a Diabetes Autoantibody Standardization Program Sample Subset Thomas O. Metz,* , Wei-Jun Qian, Jon M. Jacobs, Marina A. Gritsenko, Ronald J. Moore, Ashoka D. Polpitiya, Matthew E. Monroe, David G. Camp, II, Patricia W. Mueller, and Richard D. Smith Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, and Diabetes and Molecular Risk Assessment Laboratory, United States Centers for Disease Control and Prevention, Atlanta, Georgia Received September 17, 2007 Novel biomarkers of type 1 diabetes must be identified and validated in initial, exploratory studies before they can be assessed in proficiency evaluations. Currently, untargeted -omics approaches are underutilized in profiling studies of clinical samples. This report describes the evaluation of capillary liquid chromatography (LC) coupled with mass spectrometry (MS) in a pilot proteomic analysis of human plasma and serum from a subset of control and type 1 diabetic individuals enrolled in the Diabetes Autoantibody Standardization Program, with the goal of identifying candidate biomarkers of type 1 diabetes. Initial high-resolution capillary LC-MS/MS experiments were performed to augment an existing plasma peptide database, while subsequent LC-FTICR studies identified quantitative differences in the abundance of plasma proteins. Analysis of LC-FTICR proteomic data identified five candidate protein biomarkers of type 1 diabetes. R-2-Glycoprotein 1 (zinc), corticosteroid-binding globulin, and lumican were 2-fold up-regulated in type 1 diabetic samples relative to control samples, whereas clusterin and serotransferrin were 2-fold up-regulated in control samples relative to type 1 diabetic samples. Observed perturbations in the levels of all five proteins are consistent with the metabolic aberrations found in...
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