The Consortium for Metabonomic Toxicology (COMET)
The Consortium for Metabonomic Toxicology (COMET) was formed between five major pharmaceutical companies and Biomolecular Medicine with the aim of evaluating metabonomics as a tool in the assessment of xenobiotic toxicity.
A critical assessment of the analytical and chemometric methodologies used was conducted, including investigations of the robustness and suitability of 1H NMR spectroscopy as a profiling tool for rodent urine and serum samples. Toxicological metabonomic studies were carried out using a large number of classical toxins and conditions, and the resulting metabonomics data used to generate an expert system for the prediction of rodent kidney and liver toxicity. This expert system was delivered to the sponsoring companies and serves as a useful tool in the area of drug discovery and development.
A follow-up project, focused on the study of mechanisms of chemical toxicity was conducted and has led to a better understanding of a number of compounds which typically exhibit idiosyncratic toxicity in humans.
Key Recent Publications
Bollard ME, Contel NR, Ebbels TM, Smith L, Beckonert O, Cantor GH, Lehman-McKeeman L, Holmes EC, Lindon JC, Nicholson JK and others. 2010. NMR-based metabolic profiling identifies biomarkers of liver regeneration following partial hepatectomy in the rat. J Proteome Res 9(1):59-69
Spagou K, Wilson ID, Masson P, Theodoridis G, Raikos N, Coen M, Holmes E, Lindon JC, Plumb RS, Nicholson JK, Want EJ. HILIC-UPLC-MS for exploratory urinary metabolic profiling in toxicological studies. Anal Chem. 2011 Jan 1;83(1):382-90.
Want EJ, Coen M, Masson P, Keun HC, Pearce JT, Reily MD, Robertson DG, Rohde CM, Holmes E, Lindon JC, Plumb RS, Nicholson JK. Ultra performance liquid chromatography-mass spectrometry profiling of bile acid metabolites in biofluids: application to experimental toxicology studies. Anal Chem. 2010 Jun 15;82(12):5282-9.
Coen M, Want EJ, Clayton TA, Rhode CM, et al. Mechanistic Aspects and Novel Biomarkers of Responder and Non-Responder Phenotypes in Galactosamine-Induced Hepatitis. J Proteome Res. 2009 Oct 12.
Cavill R, Keun HC, Holmes E, Lindon JC, Nicholson JK, Ebbels TM. 2009. Genetic algorithms for simultaneous variable and sample selection in metabonomics. Bioinformatics 25(1):112-8.
Ebbels TMD, Keun HC, Beckonert OP, Bollard ME, Lindon JC, Holmes E, Nicholson JK. 2007. Prediction and classification of drug toxicity using probabilistic modeling of temporal metabolic data: The Consortium on Metabonomic Toxicology screening approach. Journal of Proteome Research 6(11):4407-22.
Lindon JC, Keun HC, Ebbels TM, Pearce JM, Holmes E, Nicholson JK. 2005. The Consortium for Metabonomic Toxicology (COMET): aims, activities and achievements. Pharmacogenomics 6(7):691-9.
