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Biomarker Discovery by Sparse Canonical Correlation Analysis of Complex Clinical Phenotypes of Tuberculosis and Malaria

Rousu, J; Agranoff, DD; Sodeinde, O; Shawe-Taylor, J; Fernandez-Reyes, D; (2013) Biomarker Discovery by Sparse Canonical Correlation Analysis of Complex Clinical Phenotypes of Tuberculosis and Malaria. PLoS Computational Biology , 9 (4) , Article e1003018. 10.1371/journal.pcbi.1003018. Green open access

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Abstract

Biomarker discovery aims to find small subsets of relevant variables in ‘omics data that correlate with the clinical syndromes of interest. Despite the fact that clinical phenotypes are usually characterized by a complex set of clinical parameters, current computational approaches assume univariate targets, e.g. diagnostic classes, against which associations are sought for. We propose an approach based on asymmetrical sparse canonical correlation analysis (SCCA) that finds multivariate correlations between the ‘omics measurements and the complex clinical phenotypes. We correlated plasma proteomics data to multivariate overlapping complex clinical phenotypes from tuberculosis and malaria datasets. We discovered relevant ‘omic biomarkers that have a high correlation to profiles of clinical measurements and are remarkably sparse, containing 1.5–3% of all ‘omic variables. We show that using clinical view projections we obtain remarkable improvements in diagnostic class prediction, up to 11% in tuberculosis and up to 5% in malaria. Our approach finds proteomic-biomarkers that correlate with complex combinations of clinical-biomarkers. Using the clinical-biomarkers improves the accuracy of diagnostic class prediction while not requiring the measurement plasma proteomic profiles of each subject. Our approach makes it feasible to use omics' data to build accurate diagnostic algorithms that can be deployed to community health centres lacking the expensive ‘omics measurement capabilities.

Type: Article
Title: Biomarker Discovery by Sparse Canonical Correlation Analysis of Complex Clinical Phenotypes of Tuberculosis and Malaria
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pcbi.1003018
Publisher version: http://dx.doi.org/10.1371/journal.pcbi.1003018
Language: English
Additional information: Copyright: © 2013 Rousu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: JR was financially supported by an Academy of Finland grant 118653 (ALGODAN) and in part by the IST Programme of the European Community, under the PASCAL2 Network of Excellence, ICT-2007-216886. DFR laboratory is supported by the UK Medical Research Council Funding no: U117585869. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/1393868
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