Metabonomics: A platform for studying drug toxicity and gene function

Nature Reviews Drug Discovery

Volumn 1, Issue 2, 2002, Pages 153-161

  Nicholson, Jeremy K ^a   Connelly, John ^a   Lindon, John C ^a   Holmes, Elaine ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 BROMOETHYLAMINE; ACYL COENZYME A; ACYL COENZYME A DEHYDROGENASE; BIOLOGICAL MARKER; CADMIUM;

ANALYTIC METHOD; BIOCHEMISTRY; BIOTRANSFORMATION; BODY FLUID; CHEMICAL STRUCTURE; GENE FUNCTION; METABOLIC PARAMETERS; METABOLISM; NEPHROTOXICITY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PHARMACEUTICAL ENGINEERING; PRINCIPAL COMPONENT ANALYSIS; PRIORITY JOURNAL; REVIEW; ANIMAL; DRUG DESIGN; DRUG EFFECT; DRUG INDUSTRY; GENE; GENOMICS; HUMAN; KIDNEY; LIVER; METHODOLOGY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHYSIOLOGY; TOXICOLOGY;

ANIMALS; DRUG DESIGN; DRUG INDUSTRY; GENES; GENOMICS; HUMANS; KIDNEY; LIVER; MAGNETIC RESONANCE SPECTROSCOPY; TOXICOLOGY;

EID: 0036463681     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd728     Document Type: Review

References (86)

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).
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).
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. 48, 182-191 (2001).
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).
5. 1H NMR spectra of urine: a nonlinear mapping approach to the classification of toxicological data. NMR Biomed. 3, 166-172 (1990).
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).
7. 1H NMR urinalysis studies on the biochemical effects of acute cadmium exposure in the rat. Mol. Pharmacol. 36, 398-404 (1989).
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).
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).
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).
11. Holmes, E. et al. Chemometric models for toxicity based on NMR spectra of biofluids. Chem. Res. Toxicol. 13, 471-478 (2000),
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 C57BL 10J and Alpk:ApfCD mouse. FEBS Lett. 484, 169-174 (2000).
13. 1H NMR spectroscopic and pattern recognition study into dystrophic tissue. Anal. Biochem. 293, 16-21 (2001).
14. Smith, L. L. Key challenges for toxicologists in the 21st century. Trends Pharmacol. Sci. 22, 281-285 (2001).
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).
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).
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).
18. Johnston, M. The yeast genome: on the road to the Golden Age. Curr. Opin. Genet. Dev. 10, 617-623 (2000).
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).
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).
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).
22. Ramos, L. S. Characterisation of Mycobacteria species by HPLC and pattern recognition. J. Chromatogr. Sci. 32, 219-227 (1994).
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).
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).
25. 1H NMR spectroscopy of urine combined with pattern recognition. NMR Biomed. 11, 1-10 (1998).
26. Griffin, J. L. et al. The initial pathogenesis of cadmium induced renal toxicity. FEBS Lett. 478, 147-150 (2000).
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).
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).
29. 1H nuclear magnetic resonance spectra by the application of chemometric techniques. Magn. Reson. Med. 28, 214-236 (1992).
30. 1H NMR spectra from perchloric avid extracts of human brain biopsies. Magn. Reson. Med. 39, 869-877 (1998).
31. El-Deredy, W. Pattern recognition approaches in biomedical and clinical magnetic resonance spectroscopy: a review. NMR Biomed. 10, 99-124 (1997).
32. 1H NMR spectroscopic studies on dynamic biochemical processes in incubated human seminal fluid samples. Biochim. Biophys. Acta 1379, 367-380 (1998).
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).
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).
35. 1H NMR spectroscopy of urine. Clin. Chem. 44, 1256-1261 (1998).
36. Beckwith-Hall, B. M. et al. Nuclear magnetic resonance spectroscope and principal components analysis investigations into biochemical effects of three model hepatotoxins. Chem. Res. Toxicol. 11, 260-272 (1998).
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).
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).
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).
40. 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).
41. 1H NMR spectroscopy of urine and pattern recognition. Anal. Biochem. 295, 194-202 (2001).
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).
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).
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).
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).
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).
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. 73, F153-F157 (1995).
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).
49. 1H nuclear magnetic resonance spectra of human urine from normal and pathological states. Anal. Biochem. 220, 284-296 (1994).
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).
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).
52. Cutler, P. et al. An integrated proteomic approach to studying glomerular nephrotoxicity. Bectrophoresis 20, 3647-3658 (1999).
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).
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).
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).
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).
57. 1H NMR spectroscopy. Toxicol. Lett 81, 15-21 (1995).
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).
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).
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).
61. Nicholson, J. K. & Wilson, I. D. High resolution proton NMR spectroscopy of biological fluids. Prog. Nucl. Magn. Reson. Spectrosc. 21, 449-501 (1989).
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).
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).
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).
65. 13C NMR spectroscopy of human blood plasma. Anal. Chem. 67, 793-811 (1995).
66. 1H diffusion-edited total correlation spectroscopy. Anal. Chem. 69, 1504-1509 (1997).
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).
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).
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).
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).
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).
72. 1H nuclear magnetic resonance analysis of intact prostatic hyperplastic and tumour tissues. Anal. Commun. 35, 113-115 (1998).
73. 1H NMR spectroscopic studies on intact rat renal cortex and medulla. Magn. Reson. Med. 41, 1108-1118 (1999).
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).
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).
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).
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).
78. Nicholls, A. W. et al. Metabonomic investigations into hydrazine toxicity in the rat. Chem. Res. Toxicol. 14, 975-987 (2001).
79. 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).
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).
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).
82. Evans, J. N. S. Biomolecular NMR Spectroscopy (Oxford Univ. Press, Oxford, 1996).
83. Manley, B. F. J. Multivariate Statistical Methods: a Primer (Chapman & Hall, London, 1986).
84. Beebe, K. R., Pell, R. J. & Seahsholt, M. B. Chemometrics: a Practical Guide (John Wiley & Sons, New York, 1998).
85. Jurs, P. C. Pattern recognition used to investigate multivariate data in analytical chemistry. Science 232, 1219-1224 (1986).
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).