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Licensed Unlicensed Requires Authentication Published by De Gruyter February 25, 2014

Variance and covariance heterogeneity analysis for detection of metabolites associated with cadmium exposure

Beatriz Valcarcel Salamanca, Timothy M.D. Ebbels and Maria De Iorio


In this study, we propose a novel statistical framework for detecting progressive changes in molecular traits as response to a pathogenic stimulus. In particular, we propose to employ Bayesian hierarchical models to analyse changes in mean level, variance and correlation of metabolic traits in relation to covariates. To illustrate our approach we investigate changes in urinary metabolic traits in response to cadmium exposure, a toxic environmental pollutant. With the application of the proposed approach, previously unreported variations in the metabolism of urinary metabolites in relation to urinary cadmium were identified. Our analysis highlights the potential effect of urinary cadmium on the variance and correlation of a number of metabolites involved in the metabolism of choline as well as changes in urinary alanine. The results illustrate the potential of the proposed approach to investigate the gradual effect of pathogenic stimulus in molecular traits.

Corresponding author: Maria De Iorio, Department of Statistical Science, University College, Gower Street, London WC1E 6BT, UK, e-mail:
a Beatriz Valcarcel Salamanca and Timothy M.D. Ebbels contributed equally to the work.


The authors gratefully acknowledge Dr Jake G Bundy, Dr Hector Keun, Dr David Spurgeon and Dr James Ellis for providing access to the cadmium and metabolic data. B.V. was supported by the Economic Social Research Council (ESRC award no. ES/H016058/1 for B.V.). M.D.I. and T.E. were partially supported by the Biotechnology and Biological Sciences Research Council (Grant Ref.BB/E20372/1). T.E. acknowledges funding from the EU 7th Framework Programme grants diXa (Grant Agreement 283775) and COSMOS (Grant Agreement 312941). This work was also partially supported by NERC project grant NE/E00895X/1.


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Published Online: 2014-2-25
Published in Print: 2014-4-1

©2014 by Walter de Gruyter Berlin/Boston

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