Metabonomics: the challenge of modelling metabolic interactions, processes and diseases in complex organisms

Elaine Holmes

Biological Chemistry, Biomedical Sciences, Imperial College, London

The role of chemometric analysis in analysing and interpreting genomic, proteomic and metabonomic data has evolved rapidly in the past decade. Metabonomics is a rapidly emerging field of research combining sophisticated analytical tools such as NMR spectroscopy and mass spectrometry with multivariate statistical analysis to generate complex metabolic profiles of biofluids and tissues. Metabonomics provides a systems approach to measuring dynamic biochemical responses of organisms to pathological stimuli or genetic modification and operates by profiling the metabolic responses of key intermediary biochemical pathways (1-3). Originally used to generate data for use in in vivo toxicological screening of drugs, the applications of metabonomics has evolved to include monitoring and evaluation of therapeutic intervention, determination of biomarkers of toxicity/ disease, identification of functional consequences of genetic modification and the characterization and prediction of a wide range of clinical conditions. The complexity and dynamic nature of biological systems present a substantial analytical challenge. Here various chemometric tools and strategies for optimizing the characterization and prediction of pathological conditions are described with particular emphasis on minimizing confounding biological and analytical ‘noise’.

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2. E. Holmes and H. Antti, Review - Chemometric contributions to the evolution of metabonomics: mathematical solutions to characterising and interpreting complex biological NMR spectra , The Analyst 127(12): 1549

3. J.T. Brindle, H. Antti, E. Holmes, G. Tranter, J.K. Nicholson, H.W.L. Bethell, S. Clarke, P.M. Schofield, E. McKilligin, D.E. Mosedale, & D.J Grainger. Rapid and Non-invasive Diagnosis of the Presence and Severity of Coronary Heart Disease Using 1H-NMR Based Metabonomics, Nature Medicine 8:(12): 1439-1444 2002