Urinary proteomics to support diagnosis of stroke

Dawson, J. , Walters, M. , Delles, C. , Mischak, H. and Mullen, W. (2012) Urinary proteomics to support diagnosis of stroke. PLoS ONE, 7(5), e35879. (doi: 10.1371/journal.pone.0035879)

Abstract

Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69), compared to controls (n = 33), and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Potentially disease-specific peptides were identified and a classifier based on these was generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. We developed two biomarker-based classifiers, employing 14 biomarkers (nominal p-value <0.004) or 35 biomarkers (nominal p-value <0.01). When tested on a blinded test set of 47 independent samples, the classification factor was significantly different between groups; for the 35 biomarker model, median value of the classifier was 0.49 (−0.30 to 1.25) in cases compared to −1.04 (IQR −1.86 to −0.09) in controls, p<0.001. The 35 biomarker classifier gave sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86. This study supports the potential for urinary proteomic biomarker models to assist with the diagnosis of acute stroke in those with mild symptoms. We now plan to refine further and explore the clinical utility of such a test in large prospective clinical trials.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Walters, Professor Matthew and Mullen, Dr Bill and Dawson, Professor Jesse and Delles, Professor Christian and Mischak, Professor Harald
• Authors: Dawson, J., Walters, M., Delles, C., Mischak, H., and Mullen, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• Published Online: 16 May 2012
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in PLoS ONE 7(5):e35879
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher