Abstract
In this review, the background to the approach known as metabonomics is provided, giving a brief historical perspective and summarizing the analytical and statistical techniques used. Some of the major applications of metabonomics relevant to pharmaceutical Research & Development are then reviewed including the study of various influences on metabolism, such as diet, lifestyle, and other environmental factors. The applications of metabonomics in drug safety studies are explained with special reference to the aims and achievements of the Consortium for Metabonomic Toxicology. Next, the role that metabonomics might have in disease diagnosis and therapy monitoring is provided with some examples, and the concept of pharmacometabonomics as a way of predicting an individual's response to treatment is highlighted. Some discussion is given on the strengths and weaknesses, opportunities of, and threats to metabonomics.
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Abbreviations
- CE:
-
capillary electrophoresis
- CLOUDS:
-
classification of unknowns by density superposition
- COMET:
-
Consortium for Metabonomic Toxicology
- COSY:
-
correlation spectroscopy
- CPMG:
-
Carr-Purcell-Meiboom-Gill (an NMR pulse sequence)
- CSF:
-
cerebrospinal fluid
- DA:
-
discriminant analysis
- FT:
-
Fourier transform
- GC:
-
gas chromatography
- HPLC:
-
high-performance liquid chromatography
- IR:
-
infrared
- LC:
-
liquid chromatography
- LIMS:
-
laboratory information management system
- MAS:
-
magic angle spinning
- MS:
-
mass spectrometry
- NMR:
-
nuclear magnetic resonance
- OSC:
-
orthogonal signal correction
- PCA:
-
principal component analysis
- PLS:
-
partial least squares
- QC:
-
quality control
- SHY:
-
statistical heterospectroscopy
- SMRS:
-
Standard Metabolic Reporting Structures
- STOCSY:
-
statistical total correlation spectroscopy
- TOCSY:
-
total correlation spectroscopy
- TOF:
-
time of flight
- TSP:
-
trimethylsilylpropionic acid sodium salt
- UPLC:
-
ultra-performance liquid chromatography
References
P. Baldi G. W. Hatfield (2002) DNA Microarrays and Gene Expression Cambridge University Press Cambridge, UK 230
J. K. Nicholson I. D. Wilson (1989) ArticleTitleHigh-resolution proton magnetic resonance spectroscopy of biological fluids Prog. Nucl. Magn. Reson. Spectrosc. 21 449–501 Occurrence Handle1:CAS:528:DyaK3cXhvVeguw%3D%3D Occurrence Handle10.1016/0079-6565(89)80008-1
K. P. R. Gartland S. M. Sanins J. K. Nicholson B. C. Sweatman C. R. Beddell J. C. Lindon (1990) ArticleTitlePattern 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 Occurrence Handle2206848 Occurrence Handle1:STN:280:By6D3c7ot1Y%3D
K. P. R. Gartland C. R. Beddell J. C. Lindon J. K. Nicholson (1991) ArticleTitleThe application of pattern recognition methods to the analysis and classification of toxicological data derived from proton NMR spectroscopy of urine Mol. Pharmacol. 39 629–642 Occurrence Handle2034235 Occurrence Handle1:CAS:528:DyaK3MXksVeltrk%3D
J. K. Nicholson J. C. Lindon E. Holmes (1999) ArticleTitle‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data Xenobiotica 29 1181–1189 Occurrence Handle10598751 Occurrence Handle1:CAS:528:DyaK1MXns12ms7k%3D Occurrence Handle10.1080/004982599238047
J. K. Nicholson J. Connelly J. C. Lindon E. Holmes (2002) ArticleTitleMetabonomics: a platform for studying drug toxicity and gene function Nat. Rev. Drug Discov. 1 153–162 Occurrence Handle12120097 Occurrence Handle1:CAS:528:DC%2BD38Xhs1aksbw%3D Occurrence Handle10.1038/nrd728
O. Fiehn (2002) ArticleTitleMetabolomics—the link between genotypes and phenotypes Plant Mol. Biol. 48 155–171 Occurrence Handle11860207 Occurrence Handle1:CAS:528:DC%2BD38Xht1Kqtr0%3D Occurrence Handle10.1023/A:1013713905833
J. K. Nicholson I. D. Wilson (2003) ArticleTitleUnderstanding ‘global’ systems biology: metabonomics and the continuum of metabolism Nat. Rev. Drug Discov. 2 668–676 Occurrence Handle12904817 Occurrence Handle1:CAS:528:DC%2BD3sXmtVGqsbs%3D Occurrence Handle10.1038/nrd1157
J. K. Nicholson E. Holmes J. C. Lindon I. D. Wilson (2004) ArticleTitleThe challenges of modeling mammalian biocomplexity Nat. Biotechnol. 22 1268–1274 Occurrence Handle15470467 Occurrence Handle1:CAS:528:DC%2BD2cXotFGqtbc%3D Occurrence Handle10.1038/nbt1015
M. Mayr Y. L. Chung U. Mayr X. K. Yin L. Ly H. Troy S. Fredericks Y. H. Yu J. R. Griffiths Q. B. Xu (2005) ArticleTitleProteomic and metabolomic analyses of atherosclerotic vessels from apolipoprotein E-deficient mice reveal alterations in inflammation, oxidative stress, and energy metabolism Arterioscler. Thromb. Vasc. Biol. 25 2135–2142 Occurrence Handle16123314 Occurrence Handle1:CAS:528:DC%2BD2MXhtVCltrnF Occurrence Handle10.1161/01.ATV.0000183928.25844.f6
R. J. A. N. Lamers E. C. H. H. Wessels J. J. M. Sandt Particlevan der K. Venema G. Schaafsma J. Greef Particlevan der H. J. J. Nesselrooij Particlevan (2003) ArticleTitleA pilot study to investigate effects of inulin on Caco-2 cells through in vitro metabolic fingerprinting J. Nutr. 133 3080–3084 Occurrence Handle14519788 Occurrence Handle1:CAS:528:DC%2BD3sXotFKrsbs%3D
S. G. Villas-Boas J. Hojer-Pedersen M. Akesson J. Smedsgaard J. Nielsen (2005) ArticleTitleGlobal metabolite analysis of yeast: evaluation of sample preparation methods Yeast 22 1155–1169 Occurrence Handle16240456 Occurrence Handle1:CAS:528:DC%2BD2MXht1ektb%2FE Occurrence Handle10.1002/yea.1308
J. E. Ippolito J. Xu S. J. Jain K. Moulder S. Mennerick J. R. Crowley R. R. Townsend J. I. Gordon (2005) ArticleTitleAn integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers Proc. Natl. Acad. Sci. USA 102 9901–9906 Occurrence Handle15998737 Occurrence Handle1:CAS:528:DC%2BD2MXmsFaru7s%3D Occurrence Handle10.1073/pnas.0500756102
M. E. Bollard J. S. Xu W. Purcell J. L. Griffin C. Quirk E. Holmes J. K. Nicholson (2002) ArticleTitleMetabolic profiling of the effects of d-galactosamine in liver spheroids using 1H NMR and MAS NMR spectroscopy Chem. Res. Toxicol. 15 1351–1359 Occurrence Handle12437325 Occurrence Handle1:CAS:528:DC%2BD38XnvFKksbw%3D Occurrence Handle10.1021/tx025571e
N. N. Kaderbhai D. I. Broadhurst D. I. Ellis D. B. Kell (2003) ArticleTitleFunctional genomics via metabolic footprinting: monitoring metabolite secretion by Escherichia coli tryptophan metabolism mutants using FT-IR and direct injection electrospray mass spectrometry Compar. Funct. Genom. 4 376–391 Occurrence Handle1:CAS:528:DC%2BD3sXnsV2jt74%3D Occurrence Handle10.1002/cfg.302
P. H. Gamache D. F. Meyer M. C. Granger I. N. Acworth (2004) ArticleTitleMetabolomic applications of electrochemistry/mass spectrometry J. Am. Soc. Mass Spectrom. 15 1717–1726 Occurrence Handle15589749 Occurrence Handle1:CAS:528:DC%2BD2cXhtVKksL%2FM Occurrence Handle10.1016/j.jasms.2004.08.016
J. C. Lindon J. K. Nicholson E. Holmes J. R. Everett (2000) ArticleTitleMetabonomics: metabolic processes studied by NMR spectroscopy of biofluids Concepts Magn. Reson. 12 289–320 Occurrence Handle1:CAS:528:DC%2BD3cXmsFOmtbg%3D Occurrence Handle10.1002/1099-0534(2000)12:5<289::AID-CMR3>3.0.CO;2-W
J. C. Lindon E. Holmes M. E. Bollard E. G. Stanley J. K. Nicholson (2004) ArticleTitleMetabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis Biomarkers 9 1–31 Occurrence Handle15204308 Occurrence Handle1:CAS:528:DC%2BD2cXkt12ms7s%3D Occurrence Handle10.1080/13547500410001668379
T. D. W. Claridge (1999) High-Resolution NMR Techniques in Organic Chemistry Elsevier Oxford, UK 384
M. Liu J. K. Nicholson J. C. Lindon (1996) ArticleTitleHigh resolution diffusion and relaxation edited one- and two-dimensional 1H NMR spectroscopy of biological fluids Anal. Chem. 68 3370–3376 Occurrence Handle8843135 Occurrence Handle1:CAS:528:DyaK28Xlt12ls74%3D Occurrence Handle10.1021/ac960426p
J. K. Nicholson P. J. D. Foxall M. Spraul R. D. Farrant J. C. Lindon (1995) ArticleTitle750 MHz 1H and 1H–13C NMR spectroscopy of human blood plasma Anal. Chem. 67 793–811 Occurrence Handle7762816 Occurrence Handle1:CAS:528:DyaK2MXjsFajurs%3D Occurrence Handle10.1021/ac00101a004
H. C. Keun O. Beckonert J. L. Griffin C. Richter D. Moskau J. C. Lindon J. K. Nicholson (2002) ArticleTitleCryogenic probe 13C NMR spectroscopy of urine for metabonomic studies Anal. Chem. 74 4588–4593 Occurrence Handle12236374 Occurrence Handle1:CAS:528:DC%2BD38Xls1Git7c%3D Occurrence Handle10.1021/ac025691r
K. E. Price S. S. Vandaveer C. E. Lunte C. K. Larive (2005) ArticleTitleTissue targeted metabonomics: metabolic profiling by microdialysis sampling and microcoil NMR J. Pharm. Biomed. Anal. 38 904–909 Occurrence Handle15876508 Occurrence Handle1:CAS:528:DC%2BD2MXns1Whtb8%3D Occurrence Handle10.1016/j.jpba.2005.02.034
A. Tomlins P. J. D. Foxall J C. Lindon J. M. Lynch M. Spraul J. R. Everett J. K. Nicholson (1998) ArticleTitleHigh resolution magic angle spinning 1H nuclear magnetic resonance analysis of intact prostatic hyperplastic and tumour tissues Anal. Commun. 35 113–115 Occurrence Handle1:CAS:528:DyaK1cXhtlaks7c%3D Occurrence Handle10.1039/a708098k
S. L. Garrod E. Humpfer M. Spraul S. C. Connor S. Polley J. Connelly J. C. Lindon J. K. Nicholson E. Holmes (1999) ArticleTitleHigh-resolution magic angle spinning 1H NMR spectroscopic studies on intact rat renal cortex and medulla Magn. Reson. Med. 41 1108–1118 Occurrence Handle10371442 Occurrence Handle1:CAS:528:DyaK1MXktVKksLc%3D Occurrence Handle10.1002/(SICI)1522-2594(199906)41:6<1108::AID-MRM6>3.0.CO;2-M
L. L. Cheng I. W. Chang D. N. Louis R. G. Gonzalez (1998) ArticleTitleCorrelation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens Cancer Res. 58 1825–1832 Occurrence Handle9581820 Occurrence Handle1:CAS:528:DyaK1cXislensbY%3D
M. Morris S. M. Watkins (2005) ArticleTitleFocused metabolomic profiling in the drug development process: advances from lipid profiling Curr. Opin. Chem. Biol. 9 407–412 Occurrence Handle15979378 Occurrence Handle1:CAS:528:DC%2BD2MXmsVOrs7Y%3D Occurrence Handle10.1016/j.cbpa.2005.06.002
I. D. Wilson J. K. Nicholson J. Castro-Perez J. H. Granger K. A. Johnson B. W. Smith R. S. Plumb (2005) ArticleTitleHigh resolution “ultra performance” liquid chromatography coupled to oa-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies J. Proteome Res. 4 591–598 Occurrence Handle15822939 Occurrence Handle1:CAS:528:DC%2BD2MXisV2js7g%3D Occurrence Handle10.1021/pr049769r
T. Soga Y. Ohashi Y. Ueno H. Nasaoka M. Tomita T. Nishioka (2003) ArticleTitleQuantitative metabolome analysis using capillary electrophoresis mass spectrometry J. Proteome Res. 2 488–494 Occurrence Handle14582645 Occurrence Handle1:CAS:528:DC%2BD3sXkvFWltrc%3D Occurrence Handle10.1021/pr034020m
J. C. Lindon J. K. Nicholson I. D. Wilson (2000) ArticleTitleDirectly-coupled HPLC-NMR and HPLC-NMR-MS in pharmaceutical research and development J. Chromatogr., B, Biomed. Sci. Appl. 748 233–258 Occurrence Handle1:CAS:528:DC%2BD3cXotF2luro%3D Occurrence Handle10.1016/S0378-4347(00)00320-0
J. C. Lindon E. Holmes J. K. Nicholson (2001) ArticleTitlePattern recognition methods and applications in biomedical magnetic resonance Prog. Nucl. Magn. Reson. Spectrosc. 39 1–40 Occurrence Handle1:CAS:528:DC%2BD3MXktVGrt7Y%3D Occurrence Handle10.1016/S0079-6565(00)00036-4
H. Wold (1985) Partial least squares S. Kotz N. L. Johnson (Eds) Encyclopedia of Statistical Sciences, Vol. 6 Wiley New York 581–591
J. Trygg S. Wold (2002) ArticleTitleOrthogonal projections to latent structures (O-PLS) J. Chemom. 16 119–128 Occurrence Handle1:CAS:528:DC%2BD38XitFClu7c%3D Occurrence Handle10.1002/cem.695
E. Holmes J. K. Nicholson G. Tranter (2001) ArticleTitleMetabonomic characterization of genetic variations in toxicological and metabolic responses using probabilistic neural networks Chem. Res. Toxicol. 14 182–191 Occurrence Handle11258967 Occurrence Handle1:CAS:528:DC%2BD3MXhtlKgsb4%3D Occurrence Handle10.1021/tx000158x
D. B. Kell (2002) ArticleTitleMetabolomics and machine learning: explanatory analysis of complex metabolome data using genetic programming to produce simple, robust rules Mol. Biol. Rep. 29 237–241 Occurrence Handle12241064 Occurrence Handle1:CAS:528:DC%2BD38Xnt1agur8%3D Occurrence Handle10.1023/A:1020342216314
O. Cloarec M. E. Dumas A. Craig R. H. Barton J. Trygg J. Hudson C. Blancher D. Gauguier J. C. Lindon E. Holmes J. Nicholson (2005) ArticleTitleStatistical total correlation spectroscopy: an exploratory approach for latent biomarker identification from metabolic 1H NMR data sets Anal. Chem. 77 1282–1289 Occurrence Handle15732908 Occurrence Handle1:CAS:528:DC%2BD2MXmsVSqsg%3D%3D Occurrence Handle10.1021/ac048630x
D. J. Crockford E. Holmes J. C. Lindon R. S. Plumb S. Zirah S. J. Bruce P. Rainville C. L. Stumpf J. K. Nicholson (2006) ArticleTitleStatistical heterospectroscopy, (SHY), an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies Anal. Chem. 78 IssueID2 363–371 Occurrence Handle16408915 Occurrence Handle1:CAS:528:DC%2BD2MXht1yrsLbJ Occurrence Handle10.1021/ac051444m
M. E. Bollard E. G. Stanley J. C. Lindon J. K. Nicholson E. Holmes (2005) ArticleTitleNMR-based metabonomics approaches for evaluating physiological influences on biofluid composition NMR Biomed. 18 143–162 Occurrence Handle15627238 Occurrence Handle1:CAS:528:DC%2BD2MXltlCrs7o%3D Occurrence Handle10.1002/nbm.935
R. S. Plumb J. H. Granger C. L. Stumpf K. A. Johnson B. W. Smith S. Gaulitz I. D. Wilson J. Castro-Perez (2005) ArticleTitleA rapid screening approach to metabonomics using UPLC and oa-TOF mass spectrometry: application to age, gender and diurnal variation in normal/Zucker obese rats and black, white and nude mice Analyst 130 844–849 Occurrence Handle15912231 Occurrence Handle1:CAS:528:DC%2BD2MXktlKru7w%3D Occurrence Handle10.1039/b501767j
J. B. German M. A. Roberts S. M. Watkins (2003) ArticleTitleGenomics and metabolomics as markers for the interaction of diet and health: lessons from lipids J. Nutr. 133 2078S–2083S Occurrence Handle12771369 Occurrence Handle1:CAS:528:DC%2BD3sXksFeqsbk%3D
K. K. Lehtimaki P. K. Valonen J. L. Griffin T. H. Vaisanen O. H. J. Grohn M. I. Kettunen J. Vepsalainen S. Yla-Herttuala J. Nicholson R. A. Kauppinen (2003) ArticleTitleMetabolite changes in BT4C rat gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death as studied by H-1 NMR spectroscopy in vivo, ex vivo, and in vitro J. Biol. Chem. 278 45915–45923 Occurrence Handle12954643 Occurrence Handle10.1074/jbc.M306209200
A. W. Nicholls R. J. Mortishire-Smith J. K. Nicholson (2003) ArticleTitleNMR spectroscopic based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats Chem. Res. Toxicol. 16 1395–1404 Occurrence Handle14615964 Occurrence Handle1:CAS:528:DC%2BD3sXotlOkt70%3D Occurrence Handle10.1021/tx0340293
L. C. Robosky D. F. Wells L. A. Egnash M. L. Manning M. D. Reily D. G. Robertson (2005) ArticleTitleMetabonomic identification of two distinct phenotypes in Sprague-Dawley (Crl:CD(SD)) rats Toxicol. Sci. 87 277–284 Occurrence Handle15933226 Occurrence Handle1:CAS:528:DC%2BD2MXovVOjs78%3D Occurrence Handle10.1093/toxsci/kfi214
Y. Wang E. Holmes J. K. Nicholson O. Cloarec J. Chollet M. Tanner B. H. Singer J. Utzinger (2004) ArticleTitleMetabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification Proc. Natl. Acad. Sci. USA 101 12676–12681 Occurrence Handle15314235 Occurrence Handle1:CAS:528:DC%2BD2cXnsVent7w%3D Occurrence Handle10.1073/pnas.0404878101
J. C. Lindon E. Holmes J. K. Nicholson (2004) ArticleTitleToxicological applications of magnetic resonance Prog. Nucl. Magn. Reson. Spectrosc. 45 109–143 Occurrence Handle1:CAS:528:DC%2BD2cXms1Ogsb0%3D Occurrence Handle10.1016/j.pnmrs.2004.05.001
E. M. Lenz J. Bright R. Knight F. R. Westwood D. Davies H. Major I. D. Wilson (2005) ArticleTitleMetabonomics with 1H-NMR spectroscopy and liquid chromatography–mass spectrometry applied to the investigation of metabolic changes caused by gentamycin-induced nephrotoxicity in the rat Biomarkers 10 173–187 Occurrence Handle16076731 Occurrence Handle1:CAS:528:DC%2BD2MXlslOms7s%3D Occurrence Handle10.1080/13547500500094034
J. C. Lindon J. K. Nicholson E. Holmes H. Antti M. E. Bollard H. Keun O. Beckonert T. M. Ebbels M. D. Reily D. Robertson G. J. Stevens P. Luke A. P. Breau G. H. Cantor R. H. Bible U. Niederhauser H. Senn G. Schlotterbeck U. G. Sidelmann S. M. Laursen A. Tymiak B. D. Car L. Lehman-McKeeman J. M. Colet A. Loukaci C. Thomas (2003) ArticleTitleContemporary issues in toxicology: the role of metabonomics in toxicology and its evaluation by the COMET project Toxicol. Appl. Pharmacol. 187 137–146 Occurrence Handle12662897 Occurrence Handle1:CAS:528:DC%2BD3sXitlWnsbk%3D Occurrence Handle10.1016/S0041-008X(02)00079-0
H. C. Keun T. M. D. Ebbels H. Antti M. Bollard O. Beckonert G. Schlotterbeck H. Senn U. Niederhauser E. Holmes J. C. Lindon J. K. Nicholson (2002) ArticleTitleAnalytical reproducibility in 1H NMR-based metabonomic urinalysis Chem. Res. Toxicol. 15 1380–1386 Occurrence Handle12437328 Occurrence Handle1:CAS:528:DC%2BD38XnvV2ntb0%3D Occurrence Handle10.1021/tx0255774
H. C. Keun T. M. D. Ebbels M. E. Bollard O. Beckonert H. Antti E. Holmes J. C. Lindon J. K. Nicholson (2004) ArticleTitleGeometric trajectory analysis of metabolic responses to toxicity can define treatment specific profiles Chem. Res. Toxicol. 17 579–587 Occurrence Handle15144214 Occurrence Handle1:CAS:528:DC%2BD2cXjtV2itLo%3D Occurrence Handle10.1021/tx034212w
T. Ebbels H. Keun O. Beckonert H. Antti M. Bollard E. Holmes J. Lindon J. Nicholson (2003) ArticleTitleToxicity classification from metabonomic data using a density superposition approach: ‘CLOUDS’ Anal. Chim. Acta 490 109–122 Occurrence Handle1:CAS:528:DC%2BD3sXmsVOltr8%3D Occurrence Handle10.1016/S0003-2670(03)00121-1
J. C. Lindon H. C. Keun T. M. D. Ebbels J. M. T. Pearce E. Holmes J. K. Nicholson (2005) ArticleTitleThe Consortium for Metabonomic Toxicology (COMET): aims, activities and achievements Pharmacogenomics 6 691–699 Occurrence Handle16207146 Occurrence Handle1:CAS:528:DC%2BD2MXhtFOhtrbP Occurrence Handle10.2217/14622416.6.7.691
M. E. Bollard H. C. Keun O. Beckonert T. M. D. Ebbels H. Antti A. W. Nicholls J. P. Shockcor G. H. Cantor G. Stevens J. C. Lindon E. Holmes J. K. Nicholson (2005) ArticleTitleComparative metabonomics of differential hydrazine toxicity in the rat and mouse Toxicol. Appl. Pharmacol. 204 135–151 Occurrence Handle15808519 Occurrence Handle1:CAS:528:DC%2BD2MXivV2iurg%3D Occurrence Handle10.1016/j.taap.2004.06.031
S. H. Moolenaar U. F. H. Engelke R. A. Wevers (2003) ArticleTitleProton nuclear magnetic resonance spectroscopy of body fluids in the field of inborn errors of metabolism Ann. Clin. Biochem. 40 16–24 Occurrence Handle12542907 Occurrence Handle1:CAS:528:DC%2BD3sXhtVyks7k%3D Occurrence Handle10.1258/000456303321016132
J. C. Lindon J. K. Nicholson J. R. Everett (1999) NMR spectroscopy of biofluids G. A. Webb (Eds) Annual Reports on NMR Spectroscopy, Vol. 38 Academic Press Oxford, UK 1–88
M. Coen M. O'Sullivan W. A. Bubb P. W. Kuchel T. Sorrell (2005) ArticleTitleProton nuclear magnetic resonance-based metabonomics for rapid diagnosis of meningitis and ventriculitis Clin. Infect. Dis. 41 1582–1590 Occurrence Handle16267730 Occurrence Handle1:CAS:528:DC%2BD2MXhtlahsbfK Occurrence Handle10.1086/497836
V. G. Dunne S. Bhattachayya M. Besser C. Rae J. L. Griffin (2005) ArticleTitleMetabolites from cerebrospinal fluid in aneurysmal subarachnoid haemorrhage correlate with vasospasm and clinical outcome: a pattern-recognition H-1 NMR study NMR Biomed. 18 24–33 Occurrence Handle15455468 Occurrence Handle1:CAS:528:DC%2BD2MXis1Wlt7g%3D Occurrence Handle10.1002/nbm.918
M. G. Swanson D. B. Vigneron Z. L. Tabatabai R. G. Males L. Schmitt P. R. Carroll J. K. James R. E. Hurd J. Kurhanewicz (2003) ArticleTitleProton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI-targeted postsurgical prostate tissues Magn. Reson. Med. 50 944–954 Occurrence Handle14587005 Occurrence Handle1:CAS:528:DC%2BD3sXps1amt70%3D Occurrence Handle10.1002/mrm.10614
D. Moka R. Vorreuther H. Schicha M. Spraul E. Humpfer M. Lipinski P. J. D. Foxall J. K. Nicholson J. C. Lindon (1998) ArticleTitleBiochemical classification of kidney carcinoma biopsy samples using magic-angle-spinning 1H nuclear magnetic resonance spectroscopy J. Pharm. Biomed. Anal. 17 125–132 Occurrence Handle9608434 Occurrence Handle1:CAS:528:DyaK1cXjtFequrw%3D Occurrence Handle10.1016/S0731-7085(97)00176-3
B. Sitter U. Sonnewald M. Spraul H. E. Fjosne I. S. Gribbestad (2002) ArticleTitleHigh-resolution magic angle spinning MRS of breast cancer tissue NMR Biomed. 15 327–337 Occurrence Handle12203224 Occurrence Handle1:CAS:528:DC%2BD38XnsVSktL8%3D Occurrence Handle10.1002/nbm.775
S. J. Barton F. A. Howe A. M. Tomlins S. A. Cudlip J. K. Nicholson B. A. Bell J. R. Griffiths (1999) ArticleTitleComparison of in vivo 1H MRS of human brain tumors with 1H HR-MAS spectroscopy of intact biopsy samples in vitro Magma 8 121–128 Occurrence Handle10456375 Occurrence Handle1:CAS:528:DyaK1MXlsFChs7Y%3D
G. L. A. H. Jones E. Sang C. Goddard R. J. Mortishire-Smith B. C. Sweatman J. N. Haselden K. Davies A. A. Grace K. Clarke J. L. Griffin (2005) ArticleTitleA functional analysis of mouse models of cardiac disease through metabolic profiling J. Biol. Chem. 280 7530–7539 Occurrence Handle15546876 Occurrence Handle1:CAS:528:DC%2BD2MXhs1yis7w%3D Occurrence Handle10.1074/jbc.M410200200
K. Odunsi R. M. Wollman C. B. Ambrosone A. Hutson S. E. McCann J. Tammela J. P. Geisler G. Miller T. Sellers W. Cliby F. Qian B. Keitz M. Intengan S. Lele J. L. Alderfer (2005) ArticleTitleDetection of epithelial ovarian cancer using H-1-NMR-based metabonomics Int. J. Cancer 113 782–788 Occurrence Handle15499633 Occurrence Handle1:CAS:528:DC%2BD2MXnvFGiug%3D%3D Occurrence Handle10.1002/ijc.20651
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 (2002) ArticleTitleRapid and noninvasive diagnosis of the presence and severity of coronary heart disease using H-1 NMR-based metabonomics Nat. Med. 8 1439–1445 Occurrence Handle12447357 Occurrence Handle1:CAS:528:DC%2BD38XptVSgtrw%3D Occurrence Handle10.1038/nm802
N. J. Waters E. Holmes A. Williams C. J. Waterfield R. D. Farrant J. K. Nicholson (2001) ArticleTitleNMR 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 Occurrence Handle11599932 Occurrence Handle1:CAS:528:DC%2BD3MXnsV2nuro%3D Occurrence Handle10.1021/tx010067f
M. Coen E. M. Lenz J. K. Nicholson I. D. Wilson F. Pognan J. C. Lindon (2003) ArticleTitleAn integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy Chem. Res. Toxicol. 16 295–303 Occurrence Handle12641429 Occurrence Handle1:CAS:528:DC%2BD3sXltlOksw%3D%3D Occurrence Handle10.1021/tx0256127
M. Coen S. U. Ruepp J. C. Lindon J. K. Nicholson F. Pognan E. M. Lenz I. D. Wilson (2004) ArticleTitleIntegrated application of transcriptomics and metabonomics yields new insight into the toxicity due to paracetamol in the mouse J. Pharm. Biomed. Anal. 35 93–105 Occurrence Handle15030884 Occurrence Handle1:CAS:528:DC%2BD2cXitFeis7w%3D Occurrence Handle10.1016/j.jpba.2003.12.019
W. H. M. Heijne R. J. A. N. Lamers P. J. Bladeren Particlevan J. P. Groten J. H. J. Nesselrooij Particlevan B. Ommen ParticleVan (2005) ArticleTitleProfiles of metabolites and gene expression in rats with chemically induced hepatic necrosis Toxicol. Pathol. 33 425–433 Occurrence Handle16036859 Occurrence Handle1:CAS:528:DC%2BD2MXksVejsLg%3D
J. L. Griffin S. A. Bonney C. Mann A. M. Hebbachi G. F. Gibbons J. K. Nicholson C. C. Shoulders J. Scott (2004) ArticleTitleAn integrated reverse functional genomic and metabolic approach to understanding orotic acid-induced fatty liver Physiol. Genomics 17 140–149 Occurrence Handle14747661 Occurrence Handle1:CAS:528:DC%2BD2cXjs1Klsr4%3D Occurrence Handle10.1152/physiolgenomics.00158.2003
T. A. Clayton, J. C. Lindon, H. Antti, C. Charuel, G. Hanton, J.-P. Provost, J.-L. Le Net, D. Baker, R. J. Walley, J. R. Everett, and J. K. Nicholson. Pharmaco-metabonomic phenotyping and personalised drug treatment. Nature in press. (2006).
J. C. Lindon J. K. Nicholson E. Holmes H. C. Keun A. Craig J. T. M. Pearce S. J. Bruce N. Hardy S.-A. Sansone H. Antti P. Jonsson C. Daykin M. Navarange R. D. Beger E. R. Verheij A. Amberg D. Baunsgaard G. H. Cantor L. Lehman-McKeeman M. Earll S. Wold E. Johansson J. N. Haselden K. Kramer C. Thomas J. Lindberg I. Schuppe-Koistinen I. D. Wilson M. D. Reily D. G. Robertson H. Senn A. Krotzky S. Kochhar J. Powell F. Ouderaa Particlevan der R. Plumb H. Schaefer M. Spraul (2005) ArticleTitleSummary recommendations for standardization and reporting of metabolic analyses Nat. Biotechnol. 23 833–838 Occurrence Handle16003371 Occurrence Handle1:CAS:528:DC%2BD2MXlvFegsr4%3D Occurrence Handle10.1038/nbt0705-833
H. Jenkins N. Hardy M. Beckmann J. Draper A. R. Smith J. Taylor O. Fiehn R. Goodacre R. J. Bino R. Hall J. Kopka G. A. Lane B. M. Lange J. R. Liu P. Mendes B. J. Nikolau S. G. Oliver N. W. Paton S. Rhee U. Roessner-Tunali K. Saito J. Smedsgaard L. W. Sumner T. Wang S. Walsh E. S. Wurtele D. B. Kell (2004) ArticleTitleA proposed framework for the description of plant metabolomics experiments and their results Nat. Biotechnol. 22 1601–1606 Occurrence Handle15583675 Occurrence Handle1:CAS:528:DC%2BD2cXhtVCku77M Occurrence Handle10.1038/nbt1041
A. L. Castle, O. Fiehn, R. Kaddurah-Daouk, and J. C. Lindon. Metabolomics standards workshop and the development of international standards for reporting metabolomics experimental results. Brief. Bioinform. (2006), in press.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lindon, J.C., Holmes, E. & Nicholson, J.K. Metabonomics Techniques and Applications to Pharmaceutical Research & Development. Pharm Res 23, 1075–1088 (2006). https://doi.org/10.1007/s11095-006-0025-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-006-0025-z