Publications
745 results found
Li M, Wang B, Zhang M, et al., 2008, Symbiotic gut microbes modulate human metabolic phenotypes, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 105, Pages: 2117-2122, ISSN: 0027-8424
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- Citations: 830
Bang J-W, Crockford DJ, Hohmes E, et al., 2008, Integrative top-down system metabolic modeling in experimental disease states via data-driven Bayesian methods, JOURNAL OF PROTEOME RESEARCH, Vol: 7, Pages: 497-503, ISSN: 1535-3893
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- Citations: 15
Bang J-W, Crockford DJ, Holmes E, et al., 2008, Integrative top-down system metabolic modeling in experimental disease states via data-driven Bayesian methods., J Proteome Res, Vol: 7, Pages: 497-503, ISSN: 1535-3893
Multivariate metabolic profiles from biofluids such as urine and plasma are highly indicative of the biological fitness of complex organisms and can be captured analytically in order to derive top-down systems biology models. The application of currently available modeling approaches to human and animal metabolic pathway modeling is problematic because of multicompartmental cellular and tissue exchange of metabolites operating on many time scales. Hence, novel approaches are needed to analyze metabolic data obtained using minimally invasive sampling methods in order to reconstruct the patho-physiological modulations of metabolic interactions that are representative of whole system dynamics. Here, we show that spectroscopically derived metabolic data in experimental liver injury studies (induced by hydrazine and alpha-napthylisothiocyanate treatment) can be used to derive insightful probabilistic graphical models of metabolite dependencies, which we refer to as metabolic interactome maps. Using these, system level mechanistic information on homeostasis can be inferred, and the degree of reversibility of induced lesions can be related to variations in the metabolic network patterns. This approach has wider application in assessment of system level dysfunction in animal or human studies from noninvasive measurements.
Saidin NA, Takayama H, Holmes E, et al., 2008, Cytotoxicity of extract of Malaysian <i>Kratom</i> and its dominant alkaloid mitragynine, on human cell lines, 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy, Publisher: GEORG THIEME VERLAG KG, Pages: 348-348, ISSN: 0032-0943
Coen M, Holmes E, Lindon JC, et al., 2008, NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology, CHEMICAL RESEARCH IN TOXICOLOGY, Vol: 21, Pages: 9-27, ISSN: 0893-228X
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- Citations: 263
Martin F-PJ, Wang Y, Sprenger N, et al., 2008, Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model, MOLECULAR SYSTEMS BIOLOGY, Vol: 4, ISSN: 1744-4292
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- Citations: 323
Saric J, Li JV, Wang Y, et al., 2008, Use of Echinostoma spp. in studies on chemotherapy and metabolic profiling
Holmes E, Nicholson JK, 2008, Human metabolic phenotyping and metabolome wide association studies, ONCOGENES MEET METABOLISM: FROM DEREGULATED GENES TO A BROADER UNDERSTANDING OF TUMOUR PHYSIOLOGY, Vol: 4, Pages: 227-249, ISSN: 1866-9425
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- Citations: 14
Nicholson JK, Holmes E, Lindon JC, 2007, Metabonomics and metabolomics techniques and their applications in mammalian systems, Handbook of Metabonomics and Metabolomics, Editors: Lindon JC, Nicholson JK, Holmes E, Publisher: Elsevier
Saric J, Wang Y, Li JV, et al., 2007, Species variation in the fecal metabolome gives insight into differential gastrointestinal function, Journal of Proteome Research, Vol: 7, Pages: 352-360
Coen M, Hong Y-S, Cloarec O, et al., 2007, Heteronuclear <SUP>1</SUP>H-<SUP>31</SUP>P statistical total correlation NMR spectroscopy of intact liver for metabolic biomarker assignment:: Application to galactosamine-induced hepatotoxicity, ANALYTICAL CHEMISTRY, Vol: 79, Pages: 8956-8966, ISSN: 0003-2700
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- Citations: 54
Leweke FM, Huang JT-J, Tsang TM, et al., 2007, Biomarker profiles in initial prodromal states of psychosis -: relation to symptoms?, NERVENARZT, Vol: 78, Pages: 285-285, ISSN: 0028-2804
Leweke FM, Huang JT-J, Tsang TM, et al., 2007, Biomarker profiles in initial prodromal states of psychosis, NERVENARZT, Vol: 78, Pages: 97-97, ISSN: 0028-2804
Ebbels TMD, Keun HC, Beckonert OP, et al., 2007, Prediction and Classification of Drug Toxicity Using Probabilistic Modeling of Temporal Metabolic Data: The Consortium on Metabonomic Toxicology Screening Approach, Journal of Proteome Research, Vol: 6, Pages: 3944-3951
Wang Y, Holmes E, Comelli EM, et al., 2007, Topographical variation in metabolic signatures of human gastrointestinal biopsies revealed by high-resolution magic-angle spinning <SUP>1</SUP>H NMR spectroscopy, JOURNAL OF PROTEOME RESEARCH, Vol: 6, Pages: 3944-3951, ISSN: 1535-3893
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- Citations: 62
Huang JT-J, Leweke FM, Tsang TM, et al., 2007, CSF metabolic and proteomic profiles in patients prodromal for psychosis, PLoS One, Vol: 2, Pages: 1-7, ISSN: 1932-6203
BackgroundThe initial prodromal state of psychosis (IPS) is defined as an early disease stage prior to the onset of overt psychosis characterized by sub-threshold or more unspecific psychiatric symptoms. Little is known regarding the biochemical changes during this period.Methodology/Principal FindingsWe investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first-onset drug naïve paranoid schizophrenia patients (n = 54) and individuals presenting with initial prodromal symptoms (n = 24), alongside healthy volunteers (n = 70) using proton nuclear magnetic resonance (1H-NMR) spectroscopy and surface enhanced laser desorption ionization (SELDI) mass spectrometry, respectively. Partial least square discriminant analysis (PLS-DA) showed that 36%/29% of IPS patients displayed proteomic/metabolic profiles characteristic of first-onset, drug naïve schizophrenia, i.e., changes in levels of glucose and lactate as well as changes in a VGF-derived peptide (VGF23-62) and transthyretin protein concentrations. However, only 29% (n = 7) of the investigated IPS patients (who to date have been followed up for up to three years) have so far received a diagnosis of schizophrenia. The presence of biochemical alterations in the IPS group did not correlate with the risk to develop schizophrenia.Conclusions/SignificanceOur results imply that schizophrenia-related biochemical disease processes can be traced in CSF of prodromal patients. However, the biochemical disturbances identified in IPS patients, at least when measured at a single time point, may not be sufficient to predict clinical outcome.
Rantalainen M, Bylesjoe M, Cloarec O, et al., 2007, Kernel-based orthogonal projections to latent structures (K-OPLS), JOURNAL OF CHEMOMETRICS, Vol: 21, Pages: 376-385, ISSN: 0886-9383
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- Citations: 50
Smith LM, Maher AD, Cloarec O, et al., 2007, Statistical correlation and projection methods for improved information recovery from diffusion-edited NMR spectra of biological samples, ANALYTICAL CHEMISTRY, Vol: 79, Pages: 5682-5689, ISSN: 0003-2700
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- Citations: 72
Vilasi A, Cutillas PR, Maher AD, et al., 2007, Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome, AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, Vol: 293, Pages: F456-F467, ISSN: 1931-857X
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- Citations: 51
Maher AD, Zirah SFM, Holmes E, et al., 2007, Experimental and analytical variation in human urine in <SUP>1</SUP>H NMR spectroscopy-based metabolic phenotyping studies, ANALYTICAL CHEMISTRY, Vol: 79, Pages: 5204-5211, ISSN: 0003-2700
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- Citations: 92
Toye AA, Dumas ME, Blancher C, et al., 2007, Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice, Diabetologia, Vol: 50, Pages: 1867-1879, ISSN: 0012-186X
Aims/hypothesis Complex changes in gene expression are associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD) promoted by feeding a high-fat diet (HFD). We used functional genomic technologies to document molecular mechanisms associated with diet-induced NAFLD. Materials and Methods Male 129S6 mice were fed a diet containing 40% fat (high-fat diet, HFD) for 15 weeks. Glucose tolerance, in vivo insulin secretion, plasma lipid profile and adiposity were determined. Plasma metabonomics and liver transcriptomics were used to identify changes in gene expression associated with HFD-induced NAFLD. Results In HFD-fed mice, NAFLD and impaired glucose and lipid homeostasis were associated with increased hepatic transcription of genes involved in fatty acid uptake, intracellular transport, modification and elongation, whilst genes involved in beta-oxidation and lipoprotein secretion were, paradoxically, also upregulated. NAFLD developed despite strong and sustained downregulation of transcription of the gene encoding stearoyl-coenzyme A desaturase 1 (Scd1) and uncoordinated regulation of transcription of Scd1 and the gene encoding sterol regulatory element binding factor 1c (Srebf1c) transcription. Inflammatory mechanisms appeared to be stimulated by HFD. Conclusions/interpretation Our results provide an accurate representation of subtle changes in metabolic and gene expression regulation underlying disease-promoting and compensatory mechanisms, collectively contributing to diet-induced insulin resistance and NAFLD. They suggest that proposed models of NAFLD pathogenesis can be enriched with novel diet-reactive genes and disease mechanisms. Electronic supplementary material The online version of this article (doi:10.1007/s00125-007-0738-5) contains supplementary material, which is available to authorised users.
Faber JH, Malmodin D, Toft H, et al., 2007, Metabonomics in Diabetes Research, J Diabetes Sci Technol, Vol: 1, Pages: 549-557
Faber JH, Malmodin D, Toft H, et al., 2007, Metabonomics in Diabetes Research, J Diabetes Sci Technol, Vol: 1, Pages: 549-557
Metabonomics has been defined as “quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification” and can provide information on disease processes, drug toxicity, and gene function. In this approach many samples of biological origin (biofluids such as urine or plasma) are analyzed using techniques that produce simultaneous detection. A variety of analytical metabolic profiling tools are used routinely, are also currently under development, and include proton nuclear magnetic resonance spectroscopy and mass spectrometry with a prior online separation step such as high-performance liquid chromatography, ultra-performance liquid chromatography, or gas chromatography. Data generated by these analytical techniques are often combined with multivariate data analysis, i.e., pattern recognition, for respectively generating and interpreting the metabolic profiles of the investigated samples. Metabonomics has gained great prominence in diabetes research within the last few years and has already been applied to understand the metabolism in a range of animal models and, more recently, attempts have been done to process complex metabolic data sets from clinical studies. A future hope for the metabonomic approach is the identification of biomarkers that are able to highlight individuals likely to suffer from diabetes and enable early diagnosis of the disease or the identification of those at risk. This review summarizes the technologies currently being used in metabonomics, as well as the studies reported related to diabetes prior to a description of the general objective of the research plan of the metabonomics part of the European Union project, Molecular Phenotyping to Accelerate Genomic Epidemiology.
Martin F-PJ, Dumas M-E, Wang Y, et al., 2007, A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model, MOLECULAR SYSTEMS BIOLOGY, Vol: 3, ISSN: 1744-4292
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- Citations: 367
Holmes E, Loo RL, Cloarec O, et al., 2007, Detection of urinary drug metabolite (Xenometabolome) signatures in molecular epidemiology studies via statistical total correlation (NMR) spectroscopy, ANALYTICAL CHEMISTRY, Vol: 79, Pages: 2629-2640, ISSN: 0003-2700
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- Citations: 97
Patki P, Craggs M, Shah J, et al., 2007, Nuclear magnetic resonance based metabonomic investigation of semen, urine and plasma metabolite profiles in healthy volunteers and men with spinal cord injury, 102nd Annual Meeting of the American-Urological-Association, Publisher: ELSEVIER SCIENCE INC, Pages: 620-620, ISSN: 0022-5347
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- Citations: 1
Marchesi J, Shanahan F, Holmes E, et al., 2007, Metabonomic signature of faecal microbiota as a contributory factor to the phenotype of IBD, Digestive Disease Weeking Meeting/ASGE Postgraduate Course Meeting, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: A361-A361, ISSN: 0016-5085
Bahn S, Leweke FM, Tsang TM, et al., 2007, Disease biomarkers in first-onset schizophrenia, 10th International Congress on Schizophrenia Research, Publisher: OXFORD UNIV PRESS, Pages: 203-203, ISSN: 0586-7614
Lindon JC, Holmes E, Nicholson JK, 2007, Metabonomics in pharmaceutical R & D, FEBS JOURNAL, Vol: 274, Pages: 1140-1151, ISSN: 1742-464X
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- Citations: 235
Bylesjo M, Rantalainen M, Cloarec O, et al., 2007, OPLS discriminant analysis:: combining the strengths of PLS-DA and SIMCA classification, JOURNAL OF CHEMOMETRICS, Vol: 20, Pages: 341-351, ISSN: 0886-9383
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- Citations: 1027
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