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Open Access Highly Accessed Methodology article

Fusion of metabolomics and proteomics data for biomarkers discovery: case study on the experimental autoimmune encephalomyelitis

Lionel Blanchet1*, Agnieszka Smolinska1, Amos Attali2, Marcel P Stoop3, Kirsten AM Ampt1, Hans van Aken2, Ernst Suidgeest2, Tinka Tuinstra2, Sybren S Wijmenga1, Theo Luider3 and Lutgarde MC Buydens1

Author Affiliations

1 Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, 6524 NP Nijmegen, The Netherlands

2 Abbott Healthcare Pharmaceuticals Nederland B.V., C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands

3 Department of Neurology, Erasmus University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

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BMC Bioinformatics 2011, 12:254  doi:10.1186/1471-2105-12-254

Published: 22 June 2011

Abstract

Background

Analysis of Cerebrospinal Fluid (CSF) samples holds great promise to diagnose neurological pathologies and gain insight into the molecular background of these pathologies. Proteomics and metabolomics methods provide invaluable information on the biomolecular content of CSF and thereby on the possible status of the central nervous system, including neurological pathologies. The combined information provides a more complete description of CSF content. Extracting the full combined information requires a combined analysis of different datasets i.e. fusion of the data.

Results

A novel fusion method is presented and applied to proteomics and metabolomics data from a pre-clinical model of multiple sclerosis: an Experimental Autoimmune Encephalomyelitis (EAE) model in rats. The method follows a mid-level fusion architecture. The relevant information is extracted per platform using extended canonical variates analysis. The results are subsequently merged in order to be analyzed jointly. We find that the combined proteome and metabolome data allow for the efficient and reliable discrimination between healthy, peripherally inflamed rats, and rats at the onset of the EAE. The predicted accuracy reaches 89% on a test set. The important variables (metabolites and proteins) in this model are known to be linked to EAE and/or multiple sclerosis.

Conclusions

Fusion of proteomics and metabolomics data is possible. The main issues of high-dimensionality and missing values are overcome. The outcome leads to higher accuracy in prediction and more exhaustive description of the disease profile. The biological interpretation of the involved variables validates our fusion approach.