Imperial College London

ProfessorElaineHolmes

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

749 results found

Wesseling H, Chan MK, Tsang TM, Ernst A, Peters F, Guest PC, Holmes E, Bahn Set al., 2013, A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology, NEUROPSYCHOPHARMACOLOGY, Vol: 38, Pages: 2532-2544, ISSN: 0893-133X

Journal article

Posma JM, Robinette SL, Holmes E, Nicholson JKet al., 2013, MetaboNetworks, an interactive Matlab-based toolbox for creating, customizing and exploring sub-networks from KEGG, Bioinformatics

MetaboNetworks is a tool to create custom sub-networks in Matlab using main reaction pairs as defined by the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and can be used to explore transgenomic interactions, for example mammalian and bacterial associations. It calculates the shortest path between a set of metabolites (e.g. biomarkers from a metabonomic study) and plots the connectivity between metabolites as links in a network graph. The resulting graph can be edited and explored interactively. Furthermore, nodes and edges in the graph are linked to the KEGG compound and reaction pair webpages.

Journal article

McPhail M, Triantafyllou E, Shawcross D, Antoniades CG, Lewis MR, Want E, Patel VC, Pasha Y, Abeles RD, Bernal W, Holmes E, Wendon J, Taylor-Robinson SDet al., 2013, Increased apoptotic activity is associated with hospital mortality and disruption in lipid homeostasis in acute-on-chronic liver failure, 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases, Publisher: WILEY-BLACKWELL, Pages: 851A-852A, ISSN: 0270-9139

Conference paper

Kirkby NS, Chan MV, Lundberg MH, Massey KA, Edmands WMB, MacKenzie LS, Holmes E, Nicolaou A, Warner TD, Mitchell JAet al., 2013, Aspirin-triggered 15-epi-lipoxin A<sub>4</sub> predicts cyclooxygenase-2 in the lungs of LPS-treated mice hut not in the circulation: implications for a clinical test, FASEB JOURNAL, Vol: 27, Pages: 3938-3946, ISSN: 0892-6638

Journal article

Tritten L, Keiser J, Godejohann M, Utzinger J, Vargas M, Beckonert O, Holmes E, Saric Jet al., 2013, Metabolic profiling framework for discovery of candidate diagnostic markers of malaria, Scientific Reports, Vol: 3, Pages: 1-7, ISSN: 2045-2322

Despite immense efforts to combat malaria in tropical and sub-tropical regions, the potency of this vector-borne disease and its status as a major driver of morbidity and mortality remain undisputed. We develop an analytical pipeline for characterizing Plasmodium infection in a mouse model and identify candidate urinary biomarkers that may present alternatives to immune-based diagnostic tools. We employ 1H nuclear magnetic resonance (NMR) profiling followed by multivariate modeling to discover diagnostic spectral regions. Identification of chemical structures is then made on the basis of statistical spectroscopy, multinuclear NMR and entrapment of candidates by iterative liquid chromatography (LC) and mass spectrometry (MS). We identify two urinary metabolites (i) 4-amino-1-[3-hydroxy-5-(hydroxymethyl)-2,3-dihydrofuran-2-yl]pyrimidin-2(1H)-one, (ii) 2-amino-4-({[5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-hydroxy-4,5-dihydrofuran-2-yl]methyl}sulfanyl)butanoic acid that were detected only in Plasmodium berghei-infected mice. These metabolites have not been described in the mammalian or parasite metabolism to date. This analytical pipeline could be employed in prospecting for infection biomarkers in human populations.

Journal article

Ismael NA, Posma JM, Frost G, Holmes E, Garcia-Perez Iet al., 2013, The role of metabonomics as a tool for augmenting nutritional information in epidemiological studies, Electrophoresis, Vol: 34, Pages: 2776-2786

Most chronic diseases have been demonstrated to have a link to nutrition. Within food and nutritional research there is a major driver to understand the relationship between diet and disease in order to improve health of individuals. However, the lack of accurate dietary intake assessment in free-living populations, makes accurate estimation of how diet is associated with disease risk difficult. Thus, there is a pressing need to find solutions to the inaccuracy of dietary reporting.Metabolic profiling of urine or plasma can provide an unbiased approach to characterizing dietary intake and various high throughput analytical platforms have been used in order to implement targeted and non-targeted assays in nutritional clinical trials and nutritional epidemiology studies.This review describes firstly the challenges presented in interpreting the relationship between diet and health within individual and epidemiological frameworks. Secondly we aim to explore how metabonomics can benefict different types of nutritional studies and discuss the critical importance of selecting appropriate analytical techniques in these studies. Thirdly we propose a strategy capable of providing accurate assessment of food intake within an epidemioligical framework in order establish accurate associations between diet and health.

Journal article

Swann JR, Spagou K, Lewis M, Nicholson JK, Glei DA, Seeman TE, Coe CL, Goldman N, Ryff CD, Weinstein M, Holmes Eet al., 2013, Microbial-Mammalian Cometabolites Dominate the Age-associated Urinary Metabolic Phenotype in Taiwanese and American Populations, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 3166-3180, ISSN: 1535-3893

Journal article

Richards SE, Wang Y, Claus SP, Lawler D, Kochhar S, Holmes E, Nicholson JKet al., 2013, Metabolic Phenotype Modulation by Caloric Restriction in a Lifelong Dog Study, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 3117-3127, ISSN: 1535-3893

Journal article

Mirnezami R, Veselkov K, Strittmatter N, Kinross JM, Goldin RD, Speller A, Jones EA, Holmes E, Abramov T, Nicholson JK, Darzi AW, Takats Zet al., 2013, Novel data processing and image co-registration algorithm for region-specific lipid profiling in colorectal cancer tissue using DESI imaging mass spectrometry, 49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X

Conference paper

Hicks L, Walker DG, Eng D, Jiminez B, Kinross J, Holmes E, Williams HR, Orchard TRet al., 2013, Urinary Metabolic Profiling of Inflammatory Bowel Disease in a South Asian Cohort, Digestive Disease Week / 28th Annual Residents and Fellows Research Conference of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S653-S653, ISSN: 0016-5085

Conference paper

Lees HJ, Swann JR, Wilson ID, Nicholson JK, Holmes Eet al., 2013, Hippurate: The Natural History of a Mammalian-Microbial Cometabolite, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 1527-1546, ISSN: 1535-3893

Journal article

Boulange CL, Claus SP, Chou CJ, Collino S, Montoliu I, Kochhar S, Holmes E, Rezzi S, Nicholson JK, Dumas ME, Martin F-PJet al., 2013, Early Metabolic Adaptation in C57BL/6 Mice Resistant to High Fat Diet Induced Weight Gain Involves an Activation of Mitochondrial Oxidative Pathways, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 1956-1968, ISSN: 1535-3893

Journal article

Ladep NG, Dona A, McPhail MJW, Shariff MI, Crossey MM, Wijeyesekera A, Okeke EN, Banwat E, Lemoine M, Njie R, Garside D, Khan SA, Thillainayagam AV, Thursz M, Holmes EC, Taylor-Robinson SDet al., 2013, URINARY METABOLIC PROFILE DISCRIMINATES HEPATOCELLULAR CARCINOMA BETTER THAN SERUM ALPHA FETOPROTEIN IN WEST AFRICANS, International Liver Congress / 48th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL), Publisher: ELSEVIER SCIENCE BV, Pages: S49-S49, ISSN: 0168-8278

Conference paper

Chan Q, Stamler J, Posma J, Garcia I, Wijeyesekera A, Griep LO, Van Horn L, Daviglus ML, Miura K, Zhao L, Nicholson JK, Holmes E, Elliott Pet al., 2013, Relationship of Coffee Consumption and its Urinary Biomarker to Blood Pressure: The Intermap Study, Scientific Sessions of the American-Heart-Association on Epidemiology and Prevention/Physical Activity, Nutrition and Metabolism, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Loo RL, Chan Q, Elliott P, Nicholson J, Holmes Eet al., 2013, Effects of a Single Unit of Different Alcoholic Beverages on Urinary Excretion Profiles, Scientific Sessions of the American-Heart-Association on Epidemiology and Prevention/Physical Activity, Nutrition and Metabolism, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Hankinson AL, Daviglus ML, Van Horn L, Chan Q, Brown I, Holmes E, Elliott P, Stamler Jet al., 2013, Diet composition and activity level of at risk and metabolically healthy obese American adults., Obesity (Silver Spring), Vol: 21, Pages: 637-643

OBJECTIVE: Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, (i) "metabolically healthy" obese, broadly defined as body mass index (BMI) ≥ 30 kg/m(2) and favorable levels of blood pressure, lipids, and glucose; and (ii) "at risk" obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi-ethnic group of 775 obese American adults ages 40-59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort. DESIGN AND METHODS: In gender-stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese. RESULTS: Nearly one in five (149/775 or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women. CONCLUSIONS: These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese.

Journal article

Seyfried F, Li JV, Miras AD, Cluny NL, Lannoo M, Fenske WK, Sharkey KA, Nicholson JK, le Roux CW, Holmes Eet al., 2013, Urinary Phenotyping Indicates Weight Loss-Independent Metabolic Effects of Roux-en-Y Gastric Bypass in Mice, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 1245-1253, ISSN: 1535-3893

Journal article

Hankinson AL, Daviglus ML, Van Horn L, Chan Q, Brown I, Holmes E, Elliott P, Stamler Jet al., 2013, Diet Composition and Activity Level of At Risk and Metabolically Healthy Obese American Adults, OBESITY, Vol: 21, Pages: 637-643, ISSN: 1930-7381

Journal article

Fonville JM, Carter CL, Pizarro L, Steven RT, Palmer AD, Griffiths RL, Lalor PF, Lindon JC, Nicholson JK, Holmes E, Bunch Jet al., 2013, Hyperspectral Visualization of Mass Spectrometry Imaging Data, ANALYTICAL CHEMISTRY, Vol: 85, Pages: 1415-1423, ISSN: 0003-2700

Journal article

Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, Kau AL, Rich SS, Concannon P, Mychaleckyj JC, Liu J, Houpt E, Li JV, Holmes E, Nicholson JK, Knights D, Ursell LK, Knight R, Gordon JIet al., 2013, Gut microbiomes of Malawian twin pairs discordant for kwashiorkor, science.

Journal article

Jimenez B, Mirnezami R, Kinross J, Cloarec O, Keun HC, Holmes E, Goldin RD, Ziprin P, Darzi A, Nicholson JKet al., 2013, <SUP>1</SUP>H HR-MAS NMR Spectroscopy of Tumor-Induced Local Metabolic "Field-Effects" Enables Colorectal Cancer Staging and Prognostication, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 959-968, ISSN: 1535-3893

Journal article

Want EJ, Masson P, Michopoulos F, Wilson ID, Theodoridis G, Plumb RS, Shockcor J, Loftus N, Holmes E, Nicholson JKet al., 2013, Global metabolic profiling of animal and human tissues via UPLC-MS, NATURE PROTOCOLS, Vol: 8, Pages: 17-32, ISSN: 1754-2189

Journal article

Cantor GH, Beckonert O, Bollard ME, Keun HC, Ebbels TMD, Antti H, Wijsman JA, Bible RH, Breau AP, Cockerell GL, Holmes E, Lindon JC, Nicholson JKet al., 2013, Integrated Histopathological and Urinary Metabonomic Investigation of the Pathogenesis of Microcystin-LR Toxicosis, VETERINARY PATHOLOGY, Vol: 50, Pages: 159-171, ISSN: 0300-9858

Journal article

Edmands WMB, Gooderham NJ, Holmes E, Mitchell SCet al., 2013, <i>S</i>-Methyl-L-cysteine sulphoxide: the Cinderella phytochemical?, TOXICOLOGY RESEARCH, Vol: 2, Pages: 11-22, ISSN: 2045-452X

Journal article

Li JV, Saric J, Yap IKS, Utzinger J, Holmes Eet al., 2013, Metabonomic investigations of age- and batch-related variations in female NMRI mice using proton nuclear magnetic resonance spectroscopy, MOLECULAR BIOSYSTEMS, Vol: 9, Pages: 3155-3165, ISSN: 1742-206X

Journal article

El Aidy S, Derrien M, Merrifield CA, Levenez F, Dore J, Boekschoten MV, Dekker J, Holmes E, Zoetendal EG, van Baarlen P, Claus SP, Kleerebezem Met al., 2012, Gut bacteria-host metabolic interplay during conventionalisation of the mouse germfree colon, ISME J, ISSN: 1751-7370

Journal article

Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JCet al., 2012, Metabolic phenotyping in clinical and surgical environments, Nature, Vol: 491, Pages: 384-392, ISSN: 0028-0836

Metabolic phenotyping involves the comprehensive analysis of biological fluids or tissue samples. This analysis allows biochemical classification of a person's physiological or pathological states that relate to disease diagnosis or prognosis at the individual level and to disease risk factors at the population level. These approaches are currently being implemented in hospital environments and in regional phenotyping centres worldwide. The ultimate aim of such work is to generate information on patient biology using techniques such as patient stratification to better inform clinicians on factors that will enhance diagnosis or the choice of therapy. There have been many reports of direct applications of metabolic phenotyping in a clinical setting.

Journal article

Posma JM, Garcia-Perez I, De Iorio M, Lindon JC, Elliott P, Holmes E, Ebbels TMD, Nicholson JKet al., 2012, Subset Optimization by Reference Matching (STORM): An optimized statistical approach for recovery of metabolic biomarker structural information from ¹H NMR spectra of biofluids, Analytical Chemistry, Vol: 84, Pages: 10694-10701, ISSN: 0003-2700

We describe a new multivariate statistical approach to recover metabolite structure information from multiple 1H NMR spectra in population sample sets. SubseT Optimization by Reference Matching (STORM) was developed to select subsets of 1H NMR spectra that contain specific spectroscopic signatures of biomarkers differentiating between different human populations. STORM aims to improve the visualization of structural correlations in spectroscopic data using these reduced spectral subsets containing smaller numbers of samples than the number of variables (n<<p). We have used ‘statistical shrinkage’ to limit the number of false positive associations and to simplify the overall interpretation of the auto-correlation matrix. The STORM approach has been applied to findings from an on-going human Metabolome-Wide Association study on Body Mass Index to identify a biomarker metabolite present in a subset of the population. Moreover, we have shown how STORM improves the visualization of more abundant NMR peaks compared to a previously published method (STOCSY). STORM is a useful new tool for biomarker discovery in the ‘omic’ sciences that has a widespread applicability. It can be applied to any type of data, provided that there is interpretable correlation among variables, and can also be applied to data with more than 1 dimension (e.g. 2D-NMR spectra).

Journal article

Holmes E, Li JV, Marchesi JR, Nicholson JKet al., 2012, Gut Microbiota Composition and Activity in Relation to Host Metabolic Phenotype and Disease Risk, CELL METABOLISM, Vol: 16, Pages: 559-564, ISSN: 1550-4131

Journal article

Anwar MA, Shalhoub J, Vorkas PA, Lim CS, Want EJ, Nicholson JK, Holmes E, Davies AHet al., 2012, <i>In-vitro</i> Identification of Distinctive Metabolic Signatures of Intact Varicose Vein Tissue via Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 44, Pages: 442-450, ISSN: 1078-5884

Journal article

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