The Consortium for Metabonomic Toxicology (COMET): aims, activities and achievements

被引:190
作者
Lindon, JC [1 ]
Keun, HC [1 ]
Ebbels, TMD [1 ]
Pearce, JMT [1 ]
Holmes, E [1 ]
Nicholson, JK [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Biomed Sci Div, London SW7 2AZ, England
关键词
chemometrics; expert system; metabonomics; nuclear magnetic resonance; pharmaceutical; toxin;
D O I
10.2217/14622416.6.7.691
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The utility of metabonomics in the evaluation of xenobiotic toxicity has been comprehensively assessed by the Consortium for Metabonomic Toxicology (COMET), formed between five major pharmaceutical companies and Imperial College London, UK. The main objectives were to assess methodologies, to generate a metabonomic database using H-1 nuclear magnetic resonance (NMR) spectroscopy of rodent urine and blood serum and to build a predictive expert system for target organ toxicity. The analytic and biologic variation that might arise through the use of metabonomics was evaluated and a high degree of robustness demonstrated. With the completion of 147 studies, the chief deliverables of a curated database of rodent biofluid NMR spectra and computer-based expert systems for the prediction of kidney or liver toxicity in rat and mouse based on the spectral data have been generated, and delivered to the sponsoring companies. The project, with its relatively modest resources, has met and exceeded all of its targets and was judged a resounding success by the sponsoring companies who are, in many cases, already enhancing and making use of the data in their in-house studies.
引用
收藏
页码:691 / 699
页数:9
相关论文
共 28 条
  • [1] Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies
    Aardema, MJ
    MacGregor, JT
    [J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2002, 499 (01) : 13 - 25
  • [2] Toxicogenomics: regulatory perspective on current position
    Battershill, JM
    [J]. HUMAN & EXPERIMENTAL TOXICOLOGY, 2005, 24 (01) : 35 - 40
  • [3] Cheng LL, 1998, CANCER RES, V58, P1825
  • [4] Cross-site comparison of gene expression data reveals high similarity
    Chu, TM
    Deng, SB
    Wolfinger, R
    Paules, RS
    Hamadeh, HK
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 2004, 112 (04) : 449 - 455
  • [5] Toxicity classification from metabonomic data using a density superposition approach: 'CLOUDS'
    Ebbels, T
    Keun, H
    Beckonert, O
    Antti, H
    Bollard, M
    Holmes, E
    Lindon, J
    Nicholson, J
    [J]. ANALYTICA CHIMICA ACTA, 2003, 490 (1-2) : 109 - 122
  • [6] EBBELS TMD, 2001, Patent No. 6683455
  • [7] Metabolomics in the opening decade of the 21st century: Building the roads to individualized health
    German, JB
    Bauman, DE
    Burrin, DG
    Failla, ML
    Freake, HC
    King, JC
    Klein, S
    Milner, JA
    Pelto, GH
    Rasmussen, KM
    Zeisel, SH
    [J]. JOURNAL OF NUTRITION, 2004, 134 (10) : 2729 - 2732
  • [8] Metabonomic studies comparing capillary and conventional HPLC-oa-TOF MS for the analysis of urine from Zucker obese rats
    Granger, J
    Plumb, R
    Castro-Perez, J
    Wilson, ID
    [J]. CHROMATOGRAPHIA, 2005, 61 (7-8) : 375 - 380
  • [9] EDGE: A centralized resource for the comparison, analysis, and distribution of toxicogenomic information
    Hayes, KR
    Vollrath, AL
    Zastrow, GM
    McMillan, BJ
    Craven, M
    Jovanovich, S
    Rank, DR
    Penn, S
    Walisser, JA
    Reddy, JK
    Thomas, RS
    Bradfield, CA
    [J]. MOLECULAR PHARMACOLOGY, 2005, 67 (04) : 1360 - 1368
  • [10] Chemometric models for toxicity classification based on NMR spectra of biofluids
    Holmes, E
    Nicholls, AW
    Lindon, JC
    Connor, SC
    Connelly, JC
    Haselden, JN
    Damment, SJP
    Spraul, M
    Neidig, P
    Nicholson, JK
    [J]. CHEMICAL RESEARCH IN TOXICOLOGY, 2000, 13 (06) : 471 - 478