ProfessorElaineHolmes

Nicholson JK, Holmes E, Lindon JC, 2007, The metabolic window into systems biology, Journal of Proteome Research, Vol: 6, ISSN: 1535-3893

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• Citations: 1

Trygg J, Holmes E, Lundstedt T, 2007, Chemometrics in metabonomics, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 469-479, ISSN: 1535-3893

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• Citations: 1028

Lindon JC, Nicholson JK, Holmes E, 2007, The Handbook of Metabonomics and Metabolomics, ISBN: 9780444528414

Molecular biology operates at three levels ? genes, proteins and metabolites. This book is unique in that it provides a comprehensive description of an approach (metabonomics) to characterise the endogenous metabolites in a living system, complementing gene and protein studies (genomics and proteomics). These "omics" methods form the basis for understanding biology at a systems level. The Handbook of Metabonomics and Metabolomics aims to be the definitive work on the rapidly expanding subjects of metabolic profiling, metabolite and biomarker identification, encompassing the fields of metabonomics and metabolomics. It covers the principles of the subject, the analytical and statistical techniques used and the wide variety of applications. © 2007 Elsevier B.V. All rights reserved.

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• Citations: 271

Martin F-PJ, Wang Y, Sprenger N, Holmes E, Lindon JC, Kochhar S, Nicholson JKet al., 2007, Effects of probiotic <i>Lactobacillus Paracasei</i> treatment on the host gut tissue metabolic profiles probed <i>via</i> magic-angle-spinning NMR spectroscopy, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 1471-1481, ISSN: 1535-3893

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• Citations: 74

Skordi E, Yap IKS, Claus SP, Martin FP, Cloarec O, Lindberg J, Schuppe-Koistinen I, Holmes E, Nicholson JKet al., 2007, Analysis of time-related metabolic fluctuations induced by ethionine in the rat, Journal of Proteome Research, Vol: 6, Pages: 4572-4581

The time-course of metabolic events following response to a model hepatotoxin ethionine (800 mg/kg) was investigated over a 7 day period in rats using high-resolution (1)H NMR spectroscopic analysis of urine and multivariate statistics. Complementary information was obtained by multivariate analysis of (1)H MAS NMR spectra of intact liver and by conventional histopathology and clinical chemistry of blood plasma. (1)H MAS NMR spectra of liver showed toxin-induced lipidosis 24 h postdose consistent with the steatosis observed by histopathology, while hypertaurinuria was suggestive of liver injury. Early biochemical changes in urine included elevation of guanidinoacetate, suggesting impaired methylation reactions. Urinary increases in 5-oxoproline and glycine suggested disruption of the gamma-glutamyl cycle. Signs of ATP depletion together with impairment of the energy metabolism were given from the decreased levels in tricarboxylic acid cycle intermediates, the appearance of ketone bodies in urine, the depletion of hepatic glucose and glycogen, and also hypoglycemia. The observed increase in nicotinuric acid in urine could be an indication of an increase in NAD catabolism, a possible consequence of ATP depletion. Effects on the gut microbiota were suggested by the observed urinary reductions in the microbial metabolites 3-/4-hydroxyphenyl propionic acid, dimethylamine, and tryptamine. At later stages of toxicity, there was evidence of kidney damage, as indicated by the tubular damage observed by histopathology, supported by increased urinary excretion of lactic acid, amino acids, and glucose. These studies have given new insights into mechanisms of ethionine-induced toxicity and show the value of multisystem level data integration in the understanding of experimental models of toxicity or disease.

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Lindon JC, Holmes E, Nicholson JK, 2007, An overview of metabonomics techniques and applications, Spectral Techniques for Proteomics, Editors: Sem, Boca Raton, Publisher: CRC Press, Pages: 321-345

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Li J, Wang Y, Fenwick A, Clayton TA, Lau YY, Legido-Quigley C, Lindon JC, Utzinger J, Holmes Eet al., 2007, A high-performance liquid chromatography and nuclear magnetic resonance spectroscopy-based analysis of commercially available praziquantel tablets, Journal of Pharmaceutical and Biomedical Analysis, Vol: 45, Pages: 263-267

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Teague CR, Dhabhar FS, Barton RH, Beckwith-Hall B, Powell J, Cobain M, Singer B, McEwen BS, Lindon JC, Nicholson JK, Holmes Eet al., 2007, Metabonomic studies on the physiological effects of acute and chronic psychological stress in Sprague-Dawley rats, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 2080-2093, ISSN: 1535-3893

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• Citations: 95

Lindon J C, Nicholson J K, Holmes E, 2007, The Handbook of Metabonomics and Metabolomics, Publisher: Elsevier, ISBN: 9780444528414

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Lindon JC, Holmes E, Nicholson JK, 2007, Global systems biology through integration of “omics” results., Handbook of Metabonomics and Metabolomics, Editors: Lindon, Nicholson, Holmes, Oxford, Publisher: Elsevier, Pages: 533-555

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Marchesi JR, Holmes E, Khan F, Kochhar S, Scanlan P, Shanahan F, Wilson ID, Wang Yet al., 2007, Rapid and noninvasive metabonomic characterization of inflammatory bowel disease, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 546-551, ISSN: 1535-3893

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• Citations: 454

Beckonert O, Keun HC, Ebbels TMD, Bundy JG, Holmes E, Lindon JC, Nicholson JKet al., 2007, Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts, NATURE PROTOCOLS, Vol: 2, Pages: 2692-2703, ISSN: 1754-2189

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• Citations: 1584

Coen M, Hong YS, Clayton TA, Rohde CM, Pearce JT, Reily MD, Robertson DG, Holmes E, Lindon JC, Nicholson JKet al., 2007, The mechanism of galactosamine toxicity revisited; A metabonomic study, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 2711-2719, ISSN: 1535-3893

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• Citations: 64

Wang Y, Lawler D, Larson B, Ramadan Z, Kochhar S, Holmes E, Nicholson JKet al., 2007, Metabonomic investigations of aging and caloric restriction in a life-long dog study, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 1846-1854, ISSN: 1535-3893

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• Citations: 130

Rantalainen M, Cloarec O, Beckonert O, Wilson ID, Jackson D, Tonge R, Rowlinson R, Rayner S, Nickson J, Wilkinson RW, Mills JD, Trygg J, Nicholson JK, Holmes Eet al., 2006, Statistically integrated metabonomic-proteomic studies on a human prostate cancer xenograft model in mice, Journal of Proteome Research, Vol: 5, Pages: 2642-2655, ISSN: 1535-3893

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Stella C, Beckwith-Hall B, Cloarec O, Holmes E, Lindon JC, Powell J, van der Ouderaa F, Bingham S, Cross AJ, Nicholson JKet al., 2006, Susceptibility of human metabolic phenotypes to dietary modulation, JOURNAL OF PROTEOME RESEARCH, Vol: 5, Pages: 2780-2788, ISSN: 1535-3893

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• Citations: 291

Holmes E, Tsang TM, Huang JT, Leweke FM, Koethe D, Gerth CW, Nolden BM, Gross S, Schreiber D, Nicholson JK, Bahn Set al., 2006, Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia, PLoS Med, Vol: 3, Pages: 1420-1428, ISSN: 1549-1277

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Craig A, Sidaway J, Holmes E, Orton T, Jackson D, Rowlinson R, Nickson J, Tonge R, Wilson I, Nicholson Jet al., 2006, Systems toxicology: Integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat, JOURNAL OF PROTEOME RESEARCH, Vol: 5, Pages: 1586-1601, ISSN: 1535-3893

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• Citations: 113

Wang Y, Holmes E, Tang H, Lindon JC, Sprenger N, Turini ME, Bergonzelli G, Fay LB, Kochhar S, Nicholson JKet al., 2006, Experimental metabonomic model of dietary variation and stress interactions, JOURNAL OF PROTEOME RESEARCH, Vol: 5, Pages: 1535-1542, ISSN: 1535-3893

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• Citations: 70

Teahan O, Gamble S, Holmes E, Waxman J, Nicholson JK, Bevan C, Keun HCet al., 2006, Impact of analytical bias in metabonomic studies of human blood serum and plasma, ANALYTICAL CHEMISTRY, Vol: 78, Pages: 4307-4318, ISSN: 0003-2700

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• Citations: 205

Crockford DJ, Lindon JC, Cloarec O, Plumb RS, Bruce SJ, Zirah S, Rainville P, Stumpf CL, Johnson K, Holmes E, Nicholson JKet al., 2006, Statistical search space reduction and two-dimensional data display approaches for UPLC-MS in biomarker discovery and pathway analysis, ANALYTICAL CHEMISTRY, Vol: 78, Pages: 4398-4408, ISSN: 0003-2700

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• Citations: 42

Holmes E, Tang H, Wang Y, Seger Cet al., 2006, The assessment of plant metabolite profiles by NMR-based methodologies, PLANTA MEDICA, Vol: 72, Pages: 771-785, ISSN: 0032-0943

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• Citations: 106

Holmes E, Tsang TM, Tabrizi SJ, 2006, The application of NMR-based metabonomics in neurological disorders., NeuroRx, Vol: 3, Pages: 358-372, ISSN: 1545-5343

Advances in postgenomic technologies have radically changed the information output from complex biological systems, generating vast amounts of high complexity data that can be interpreted by means of chemometric and bioinformatic methods to achieve disease diagnosis and prognosis. High-resolution nuclear magnetic resonance (NMR) spectroscopy of biofluids such as plasma, cerebrospinal fluid (CSF), and urine can generate robust, interpretable metabolic fingerprints that contain latent information relating to physiological or pathological status. This technology has been successfully applied to both preclinical and clinical studies of neurodegenerative diseases such as Huntington's disease, muscular dystrophy, and cerebellar ataxia. An extension of this technology, (1)H magic-angle-spinning (HRMAS) NMR spectroscopy, can be used to generate metabolic information on small intact tissue samples, providing a metabolic link between metabolic profiling of biofluids and histology. In this review we provide a summary of high-resolution NMR studies in neurodegenerative disease and explore the potential of metabonomics in evaluating disease progression with respect to therapeutic intervention.

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Holmes E, Cloarec O, Nicholson JK, 2006, Probing latent biomarker signatures and in vivo pathway activity in experimental disease states via statistical total correlation spectroscopy (STOCSY) of biofluids:: Application to HgCl₂ toxicity, JOURNAL OF PROTEOME RESEARCH, Vol: 5, Pages: 1313-1320, ISSN: 1535-3893

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• Citations: 84

Smith LM, Maibaum E, Maher A, Chan Q, Elliott P, Mancilha-Carvalho J, Stamler J, Kesteloot H, Nicholson JK, Holmes Eet al., 2006, Metabonomic characterization of nutritional and environmental signatures in human population studies, 14th Meeting of the International-Society-of-Atherosclerosis, Publisher: ELSEVIER IRELAND LTD, Pages: 390-390, ISSN: 1567-5688

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Lindon JC, Holmes E, Nicholson JK, 2006, Metabonomics techniques and applications to pharmaceutical research & development, PHARMACEUTICAL RESEARCH, Vol: 23, Pages: 1075-1088, ISSN: 0724-8741

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• Citations: 227

Loo RL, Holmes E, Maibaum E, Coen M, Ebbels T, Chan Q, Elliott P, Ueshima H, Zhou B, Stamler Jet al., 2006, Metabonomics to assess self-reported data: The international study on macronutrients and blood pressure (INTERMAP), 14th Meeting of the International-Society-of-Atherosclerosis, Publisher: ELSEVIER IRELAND LTD, Pages: 430-431, ISSN: 1567-5688

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Waters NJ, Waterfield CJ, Farrant RD, Holmes E, Nicholson JKet al., 2006, Integrated metabonomic analysis of bromobenzene-induced hepatotoxicity: Novel induction of 5-oxoprolinosis, JOURNAL OF PROTEOME RESEARCH, Vol: 5, Pages: 1448-1459, ISSN: 1535-3893

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• Citations: 94

Dumas M-E, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside J, Tatoud R, Blanc V, Lindon JC, Mitchell SC, Holmes E, McCarthy MI, Scott J, Gauguier D, Nicholson Jet al., 2006, Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice, Proc Natl Acad Sci, Vol: 103, Pages: 12511-12516, ISSN: 0027-8424

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Craig A, Cloareo O, Holmes E, Nicholson JK, Lindon JCet al., 2006, Scaling and normalization effects in NMR spectroscopic metabonomic data sets, ANALYTICAL CHEMISTRY, Vol: 78, Pages: 2262-2267, ISSN: 0003-2700

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• Citations: 396