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Differential Plasma Glycoproteome of p19 Skin Cancer Mouse Model Using the Corra Label-Free LC-MS Proteomics Platform

Letarte, Simon and Brusniak, Mi-Youn and Campbell, David and Eddes, James and Kemp, Christopher J. and Lau, Hollis and Mueller, Lukas and Schmidt, Alexander and Shannon, Paul and Kelly-Spratt, Karen S. and Vitek, Olga and Zhang, Hui and Aebersold, Ruedi and Watts, Julian D.. (2008) Differential Plasma Glycoproteome of p19 Skin Cancer Mouse Model Using the Corra Label-Free LC-MS Proteomics Platform. Clinical Proteomics, 4 (3-4). p. 105.

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Official URL: http://edoc.unibas.ch/45907/

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Abstract

A proof-of-concept demonstration of the use of label-free quantitative glycoproteomics for biomarker discovery workflow is presented here, using a mouse model for skin cancer as an example. Blood plasma was collected from 10 control mice, and 10 mice having a mutation in the p19(ARF) gene, conferring them high propensity to develop skin cancer after carcinogen exposure. We enriched for N-glycosylated plasma proteins, ultimately generating deglycosylated forms of the modified tryptic peptides for liquid chromatography mass spectrometry (LC-MS) analyses. LC-MS runs for each sample were then performed with a view to identifying proteins that were differentially abundant between the two mouse populations. We then used a recently developed computational framework, Corra, to perform peak picking and alignment, and to compute the statistical significance of any observed changes in individual peptide abundances. Once determined, the most discriminating peptide features were then fragmented and identified by tandem mass spectrometry with the use of inclusion lists. We next assessed the identified proteins to see if there were sets of proteins indicative of specific biological processes that correlate with the presence of disease, and specifically cancer, according to their functional annotations. As expected for such sick animals, many of the proteins identified were related to host immune response. However, a significant number of proteins also directly associated with processes linked to cancer development, including proteins related to the cell cycle, localisation, trasport, and cell death. Additional analysis of the same samples in profiling mode, and in triplicate, confirmed that replicate MS analysis of the same plasma sample generated less variation than that observed between plasma samples from different individuals, demonstrating that the reproducibility of the LC-MS platform was sufficient for this application. These results thus show that an LC-MS-based workflow can be a useful tool for the generation of candidate proteins of interest as part of a disease biomarker discovery effort.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Humana Press
ISSN:1542-6416
e-ISSN:1559-0275
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:29 Nov 2017 07:25
Deposited On:29 Nov 2017 07:25

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