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Metabonomics: a platform for studying drug toxicity and gene function

Abstract

The later that a molecule or molecular class is lost from the drug development pipeline, the higher the financial cost. Minimizing attrition is therefore one of the most important aims of a pharmaceutical discovery programme. Novel technologies that increase the probability of making the right choice early save resources, and promote safety, efficacy and profitability. Metabonomics is a systems approach for studying in vivo metabolic profiles, which promises to provide information on drug toxicity, disease processes and gene function at several stages in the discovery-and-development process.

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Figure 1: Relating the real world to the 'omics' world.
Figure 2: Effect of time in toxicological studies.
Figure 3: A functional NMR spectrum of rat urine.
Figure 4: Metabonomic detection of liver and kidney toxicity.
Figure 5: Principal components analysis (PCA) of rat renal papillary damage.
Figure 6: Integrated metabonomics.

References

  1. Nicholson, J. K., Lindon, J. C. & Holmes, E. 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR data. Xenobiotica 29, 1181–1189 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Lindon, J. C., Nicholson, J. K., Holmes, E. & Everett, J. R. Metabonomics: metabolic processes studied by NMR spectroscopy of biofluids. Concepts Magn. Reson. 12, 289–320 (2000).

    Article  CAS  Google Scholar 

  3. Holmes, E., Nicholson, J. K. & Tranter, G. Metabonomic classification of genetic variations in toxicological and metabolic responses using probabalistic neural networks. Chem. Res. Toxicol. 14, 182–191 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Robertson, D. G. et al. Metabonomics: evaluation of nuclear magnetic resonance (NMR) and pattern recognition technology for rapid in vivo screening of liver and kidney toxicants. Toxicol. Sci. 57, 326–337 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Gartland, K. P. R. et al. Pattern recognition analysis of high resolution 1H NMR spectra of urine: a nonlinear mapping approach to the classification of toxicological data. NMR Biomed. 3, 166–172 (1990).

    Article  CAS  PubMed  Google Scholar 

  6. Anthony, M. L., Beddell, C. R., Lindon, J. C. & Nicholson, J. K. Studies on the comparative toxicity of S-(1,2-dichlorovinyl)-l-cysteine, S-(1,2-dichlorovinyl)-homocysteine and 1,1,2-trichloro-3,3,3-trifluoro-1-propene in the Fischer 344 rat. Arch. Toxicol. 69, 99–110 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. Nicholson, J. K., Higham, D., Timbrell, J. A. & Sadler, P. J. Quantitative 1H NMR urinalysis studies on the biochemical effects of acute cadmium exposure in the rat. Mol. Pharmacol. 36, 398–404 (1989).

    CAS  PubMed  Google Scholar 

  8. Griffin, J. L., Williams, H. J., Sang, E. & Nicholson, J. K. Abnormal lipid profile of dystrophic cardiac tissue as demonstrated by one- and two-dimensional magic angle spinning NMR spectroscopy. Magn. Reson. Med. 46, 249–255 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Phipps, A. N., Stewart, J., Wright, B. & Wilson, I. D. Effect of diet on the urinary excretion of hippuric acid and other dietary derived aromatics in the rat. Xenobiotica 28, 527–537 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Holmes, E. et al. Identification of novel biomarkers of renal toxicity using automatic data reduction techniques and PCA of proton NMR spectra of urine. Chemometr. Intell. Lab. Syst. 44, 251–261 (1998).

    Article  Google Scholar 

  11. Holmes, E. et al. Chemometric models for toxicity based on NMR spectra of biofluids. Chem. Res. Toxicol. 13, 471–478 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Gavaghan, C. L., Holmes, E., Lenz, E., Wilson, I. D. & Nicholson, J. K. An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences; application to the C57BL10J and Alpk:ApfCD mouse. FEBS Lett. 484, 169–174 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Griffin, J. L. et al. Metabolic profiling of genetic disorders: a multi-tissue 1H NMR spectroscopic and pattern recognition study into dystrophic tissue. Anal. Biochem. 293, 16–21 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Smith, L. L. Key challenges for toxicologists in the 21st century. Trends Pharmacol. Sci. 22, 281–285 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Delneri, D., Brancia, F. L. & Oliver, S. G. Towards a truly integrative biology through the functional genomics of yeast. Curr. Opin. Biotechnol. 12, 87–91 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Raamsdonk, L. M. et al. A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nature Biotechnol. 19, 45–50 (2001).

    Article  CAS  Google Scholar 

  17. Kettaneh, N., Berglund, A. & Wold, S. in Proceedings of the PLS '01 International Symposium (eds Vinzi, V. E., Lauro, C., Morineau, A. & Tenenhaus, M.) 1 (CICIA Ceresta, Paris, 2001).

    Google Scholar 

  18. Johnston, M. The yeast genome: on the road to the Golden Age. Curr. Opin. Genet. Dev. 10, 617–623 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Goodacre, R., Rooney, P. J. & Kell, D. B. Discrimination between methicillin-resistant and methicillin-susceptible Staphylococcus aureus using pyrolysis mass spectrometry and artificial neural networks. J. Antimicrob. Chemother. 41, 27–34 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Freeman, R. et al. Rapid identification of species within the Mycobacterium tuberculosis complex by artificial neural network analysis of pyrolysis mass spectra. J. Med. Microbiol. 40, 170–173 (1994).

    Article  CAS  PubMed  Google Scholar 

  21. Halket, J. M. et al. Deconvolution of gas chromatography/mass spectrometry of urinary organic acids – potential for pattern recognition and automated identification of metabolic disorders. Rapid Commun. Mass Spectrom. 13, 279–284 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Ramos, L. S. Characterisation of Mycobacteria species by HPLC and pattern recognition. J. Chromatogr. Sci. 32, 219–227 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Vigneau-Calahan, K. E., Shestopalov, A. I., Milbury, P. E., Matson, W. R. & Kristal, B. S. Characterisation of diet-dependent metabolic serotypes: analytical and biological variability issues in rats. J. Nutr. 131, S924–S932 (2001).

    Article  Google Scholar 

  24. Winson, M. K. et al. Diffuse reflectance absorbance spectroscopy taking in chemometrics (DRASTIC). A hyperspectral FT-IR-based approach to rapid screening for metabolite overproduction. Anal. Chim. Acta 348, 273–282 (1997).

    Article  CAS  Google Scholar 

  25. Holmes, E. et al. Development of a model for classification of toxin-induced lesions using 1H NMR spectroscopy of urine combined with pattern recognition. NMR Biomed. 11, 1–10 (1998).

    Article  Google Scholar 

  26. Griffin, J. L. et al. The initial pathogenesis of cadmium induced renal toxicity. FEBS Lett. 478, 147–150 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Nicholls, A., Nicholson, J. K., Haselden, J. N. & Waterfield, C. J. A metabonomic approach to the investigation of drug-induced phospholipidosis. Biomarkers 5, 410–423 (2000).

    Article  CAS  Google Scholar 

  28. Espina, J. R. et al. Detection of in vivo biomarkers of phospholipidosis using NMR-based metabonomic approaches. Magn. Reson. Chem. 39, 559–565 (2001).

    Article  CAS  Google Scholar 

  29. Howells, S. L., Maxwell, R. J., Peet, A. C. & Griffiths, J. R. An investigation of tumour 1H nuclear magnetic resonance spectra by the application of chemometric techniques. Magn. Reson. Med. 28, 214–236 (1992).

    Article  CAS  PubMed  Google Scholar 

  30. Maxwell, R. J. et al. Pattern recognition analysis of 1H NMR spectra from perchloric avid extracts of human brain biopsies. Magn. Reson. Med. 39, 869–877 (1998).

    Article  CAS  PubMed  Google Scholar 

  31. El-Deredy, W. Pattern recognition approaches in biomedical and clinical magnetic resonance spectroscopy: a review. NMR Biomed. 10, 99–124 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Tomlins, A. M. et al. High resolution 1H NMR spectroscopic studies on dynamic biochemical processes in incubated human seminal fluid samples. Biochim. Biophys. Acta 1379, 367–380 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. Griffin, J. L., Walker, L. A., Shore, R. F. & Nicholson, J. K. Metabolic profiling of chronic cadmium exposure in the rat. Chem. Res. Toxicol. 14, 1428–1434 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Foxall, P. J. D. & Nicholson, J. K. Nuclear magnetic resonance spectroscopy: a non-invasive probe of kidney metabolism and function. Exp. Nephrol. 6, 409–414 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Bairaktari, E., Katopodis, K., Siamopoulos, K. C. & Tsolas, O. Paraquat-induced renal injury studied by 1H NMR spectroscopy of urine. Clin. Chem. 44, 1256–1261 (1998).

    CAS  PubMed  Google Scholar 

  36. Beckwith-Hall, B. M. et al. Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins. Chem. Res. Toxicol. 11, 260–272 (1998).

    Article  CAS  PubMed  Google Scholar 

  37. Ghauri, F., McLean, A., Beales, D., Wilson, I. D. & Nicholson, J. K. Induction of 5-oxoprolinuria in the rat following chronic feeding with N-acetyl 4-aminophenol (paracetamol). Biochem. Pharmacol. 46, 953–957 (1993).

    Article  CAS  PubMed  Google Scholar 

  38. Holmes, E., Bonner, F. & Nicholson, J. K. Comparative studies on the nephrotoxicity of 2-bromoethanamine hydrobromide in the Fisher 344 rat and the multimammate desert mouse (Mastomys natalensis). Arch. Toxicol. 70, 89–95 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Holmes, E., Bonner, F. & Nicholson, J. K. Comparative biochemical effects of low doses of mercury II chloride in the F344 rat and the multimammate mouse (Mastomys natalensis). Comp. Biochem. Physiol. C 114, 7–15 (1996).

    CAS  PubMed  Google Scholar 

  40. Holmes, E., Bonner, F. & Nicholson, J. K. 1H NMR spectroscopic and histopathological studies on propylene imine induced renal papillary necrosis in the rat and the multimammate desert mouse (Mastomys natalensis). Comp. Biochem. Physiol. C 116, 125–134 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Bollard, M. E. et al. Investigations into biochemical changes due to diurnal variation and estrus cycle in female rats using high resolution 1H NMR spectroscopy of urine and pattern recognition. Anal. Biochem. 295, 194–202 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Gavaghan, C. L. et al. HPLC–NMR spectroscopic and chemometric studies on metabolic variation in Sprague Dawley rats. Anal. Biochem. 291, 245–252 (2001).

    Article  CAS  PubMed  Google Scholar 

  43. Moolenaar, S. H. et al. β-Ureidopropionase deficiency: a novel inborn error of metabolism discovered using NMR spectroscopy on urine. Magn. Reson. Med. 46, 1014–1017 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Moolenaar, S. H. et al. In vivo and in vitro NMR spectroscopy reveal a putative novel inborn error involving polyol metabolism. NMR Biomed. 14, 167–176 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. Burns, S. P., Holmes, H. C., Chalmers, R. A., Johnson, A. & Iles, R. A. Proton NMR spectroscopic analysis of multiple acyl-CoA dehydrogenase deficiency – capacity of the choline oxidation pathway for methylation in vivo. Biochim. Biophys. Acta 1406, 274–282 (1998).

    Article  CAS  PubMed  Google Scholar 

  46. Neild, G. H., Foxall, P. J. D., Lindon, J. C., Holmes, E. & Nicholson, J. K. Uroscopy in the 21st century: high field NMR spectroscopy. Nephrol. Dial. Transplant. 12, 404–417 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Foxall, P. J. D., Bewley. S., Neild, G., Rodeck, C. H. & Nicholson, J. K. Analysis of fetal and neonatal urine using proton NMR spectroscopy. Arch Dis Child Fetal Neonatal Ed 73, F153–F157 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Foxall, P. J. D. et al. Proton nuclear magnetic resonance studies of early ifosfamide-induced nephrotoxicity in man: ifosfamide-induced encephalopathy and glutaric aciduria. Clin. Cancer Res. 3, 1507–1518 (1997).

    CAS  PubMed  Google Scholar 

  49. Holmes, E. et al. Automatic data reduction and pattern recognition methods for analysis of 1H nuclear magnetic resonance spectra of human urine from normal and pathological states. Anal. Biochem. 220, 284–296 (1994).

    Article  CAS  PubMed  Google Scholar 

  50. Gygi, S. P., Rochon, Y., Franza, B. R. & Aebersold, R. Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol. 19, 1720–1730 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tweeddale, H., Notley-McRobb, L. & Ferenci, T. Effect of slow growth on metabolism of Escherichia coli, as revealed by global metabolite pool ('metabolome') analysis. J. Bacteriol. 180, 5109–5116 (1988).

    Google Scholar 

  52. Cutler, P. et al. An integrated proteomic approach to studying glomerular nephrotoxicity. Electrophoresis 20, 3647–3658 (1999).

    Article  CAS  PubMed  Google Scholar 

  53. Nicholson, J. K., Buckingham, M. J. & Sadler, P. J. High resolution proton NMR studies of vertebrate blood and plasma. Biochem. J. 211, 605–615 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bales, J. R., Higham, D. P., Howe, I., Nicholson, J. K. & Sadler, P. J. Use of high resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin. Chem. 30, 426–432 (1984).

    CAS  PubMed  Google Scholar 

  55. Nicholson, J. K. et al. Proton NMR studies of serum, plasma and urine from fasting normal, and diabetic subjects. Biochem. J. 217, 365–375 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Nicholson, J. K., Timbrell, J. A., & Sadler, P. J. Proton NMR spectra of urine as indicators of renal damage: mercury nephrotoxicity in rats. Mol. Pharmacol. 27, 644–651 (1985).

    CAS  PubMed  Google Scholar 

  57. Halligan, S. et al. A study of the nephrotoxicity of three cephalosporins in rabbits using 1H NMR spectroscopy. Toxicol. Lett. 81, 15–21 (1995).

    Article  CAS  PubMed  Google Scholar 

  58. Gartland, K. P. R., Beddell, C., Lindon, J. C. & Nicholson, J. K. The application of pattern recognition methods to the analysis and classification of toxicological data derived from NMR spectroscopy of urine. Mol. Pharmacol. 39, 629–642 (1991).

    CAS  PubMed  Google Scholar 

  59. Holmes, E. et al. NMR spectroscopy and pattern recognition analysis of the biochemical processes associated with the progression and recovery from nephrotoxic lesions in the rat induced by mercury (II) chloride and 2-bromoethanamine. Mol. Pharmacol. 42, 922–930 (1992).

    CAS  PubMed  Google Scholar 

  60. Ghauri, F., Wilson, I. D., Parkes, H. G. & Nicholson, J. K. Asymptomatic 5-oxoprolinuria in man detected by proton NMR spectroscopy of urine. Clin. Chem. 39, 1341 (1993).

    CAS  PubMed  Google Scholar 

  61. Nicholson, J. K. & Wilson, I. D. High resolution proton NMR spectroscopy of biological fluids. Prog. Nucl. Magn. Reson. Spectrosc. 21, 449–501 (1989).

    Article  CAS  Google Scholar 

  62. Lynch, M. J. & Nicholson, J. K. Proton MRS of human prostatic fluid: correlations between citrate, spermine and myo-inositol and changes with disease. Prostate 30, 248–255 (1997).

    Article  CAS  PubMed  Google Scholar 

  63. Lindon, J. C., Holmes, E. & Nicholson, J. K. Pattern recognition methods and applications in biomedical magnetic resonance. Prog. Nucl. Magn. Reson. Spectrosc. 39, 1–40 (2001).

    Article  CAS  Google Scholar 

  64. Ghauri, F. Y. K. et al. NMR spectrosocopy of human post mortem cerebrospinal fluid: distinction of Alzheimer's disease from control using pattern recognition and statistics. NMR Biomed. 6, 163–167 (1993).

    Article  CAS  PubMed  Google Scholar 

  65. Nicholson, J. K., Foxall, P., Spraul, M., Farrant, R. D. & Lindon, J. C. 750 MHz 1H and 1H–13C NMR spectroscopy of human blood plasma. Anal. Chem. 67, 793–811 (1995).

    Article  CAS  PubMed  Google Scholar 

  66. Liu, M., Nicholson, J. K., Parkinson, J. A. & Lindon, J. C. Measurement of biomolecular diffusion coefficients in blood plasma using two-dimensional 1H–1H diffusion-edited total correlation spectroscopy. Anal. Chem. 69, 1504–1509 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Shockcor, J. et al. Combined hyphenation of HPLC, NMR spectroscopy and ion-trap mass spectrometry (HPLC–NMR–MS) with application to the detection and characterization of xenobiotic and endogenous metabolites in human urine. Anal. Chem. 68, 4431–4435 (1996).

    Article  CAS  PubMed  Google Scholar 

  68. Spraul, M. et al. Flow injection NMR spectroscopy of biofluids for rapid structural studies and high throughput biochemical screening. Anal. Commun. 34, 339–341 (1997).

    Article  CAS  Google Scholar 

  69. Moka, D. et al. Magic angle spinning proton nuclear magnetic resonance spectroscopic analysis of intact kidney tissue samples. Anal. Commun. 34, 107–109 (1997).

    Article  CAS  Google Scholar 

  70. Cheng, L. L. et al. Enhanced resolution of proton NMR spectra of malignant lymph nodes using magic angle spinning. Magn. Reson. Med. 36, 653–658 (1996).

    Article  CAS  PubMed  Google Scholar 

  71. Cheng, L. L. et al. Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc. Natl Acad. Sci. USA 94, 6408–6413 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Tomlins, A. et al. High resolution magic angle spinning 1H nuclear magnetic resonance analysis of intact prostatic hyperplastic and tumour tissues. Anal. Commun. 35, 113–115 (1998).

    Article  CAS  Google Scholar 

  73. Garrod, S. L. et al. High resolution MAS-1H NMR spectroscopic studies on intact rat renal cortex and medulla. Magn. Reson. Med. 41, 1108–1118 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Waters, N. J. et al. High resolution magic angle spinning NMR spectroscopy of intact liver and kidney: optimisation of sample preparation procedures and biochemical stability of tissue during spectral acquisition. Anal. Biochem. 282, 16–23 (2000).

    Article  CAS  PubMed  Google Scholar 

  75. Bollard, M., Holmes, E., Lindon, J. C. & Nicholson J. K. MAS-NMR studies on rat liver: assignment of glycogen resonances. Magn. Reson. Med. 44, 201–207 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Millis, K., Maas, E., Cory, D. G. & Singer, S. Gradient enhanced high resolution magic angle spinning nuclear magnetic resonance spectroscopy of human adipocyte tissue. Magn. Reson. Med. 38, 399–403 (1997).

    Article  CAS  PubMed  Google Scholar 

  77. Griffin, J. L. et al. The biochemical profile of rat testicular tissue as measured by magic angle spinning NMR spectroscopy. FEBS Lett. 486, 225–229 (2000).

    Article  CAS  PubMed  Google Scholar 

  78. Nicholls, A. W. et al. Metabonomic investigations into hydrazine toxicity in the rat. Chem. Res. Toxicol. 14, 975–987 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Garrod, S. et al. High resolution 1H NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in intact renal and hepatic tissue. Magn. Reson. Med. 45, 781–790 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Waters, N. J. et al. NMR and pattern recognition studies on the time-related metabolic effects of α-naphthylisothiocyanate on liver, urine, and plasma in the rat: an integrative metabonomic approach. Chem. Res. Toxicol. 14, 1401–1412 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Griffin, J. L., Mann, C. J., Scott, J., Shoulders, C. C. & Nicholson, J. K. Choline containing metabolites during cell transfection: an insight into magnetic resonance spectroscopy detectable changes. FEBS Lett. 509, 263–266 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Evans, J. N. S. Biomolecular NMR Spectroscopy (Oxford Univ. Press, Oxford, 1996).

    Google Scholar 

  83. Manley, B. F. J. Multivariate Statistical Methods: a Primer (Chapman & Hall, London, 1986)

    Google Scholar 

  84. Beebe, K. R., Pell, R. J. & Seahsholt, M. B. Chemometrics: a Practical Guide (John Wiley & Sons, New York, 1998)

    Google Scholar 

  85. Jurs, P. C. Pattern recognition used to investigate multivariate data in analytical chemistry. Science 232, 1219–1224 (1986).

    Article  CAS  PubMed  Google Scholar 

  86. Eriksson, L., Johansson, E., Kettanah-Wold, N. & Wold, S. Introduction to Multi- and Megavariate Data Analysis Using Projection Methods (PCA and PLS) (UMETRICS, Sweden, 1999)

    Google Scholar 

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Acknowledgements

We thank I. Wilson, (AstraZeneca Pharmaceuticals, UK), J. Everett, (Pfizer Global Research, UK) and D. Robertson (Pfizer Global Research, USA) for helpful discussions on the philosophy of metabonomics. We are grateful to M. Spraul and Bruker Analytik GmbH, Germany, for help with many metabonomics projects. Particular thanks are due to H. Antti, A. Nicholls, C. Gavaghan and J. Bundy for data collection and help with data processing. We thank J. Azmi for her help with the α-naphthylisothiocyanate data and analysis. We also thank The Engineering and Physical Sciences Research Council, the Medical Research Council, the Natural Environment Research Council and the Biotechnology and Biological Sciences Research Council for funding this and related work over many years.

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Correspondence to Jeremy K. Nicholson.

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Nicholson, J., Connelly, J., Lindon, J. et al. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 1, 153–161 (2002). https://doi.org/10.1038/nrd728

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