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University of Birmingham Metabolomics enables precision medicine: “A White Paper, Community Perspective” Beger, Richard D.; Dunn, Warwick; Schmidt, Michael A.; Gross, Steven S.; Kirwan, Jennifer A.; Cascante, Marta; Brennan, Lorraine; Wishart, David S.; Oresic, Matej; Hankemeier, Thomas; Broadhurst, David I.; Lane, Andrew N.; Suhre, Karsten; Kastenmüller, Gabi; Sumner, Susan J.; Thiele, Ines; Fiehn, Oliver; Kaddurah-daouk, Rima DOI: 10.1007/s11306-016-1094-6 License: Creative Commons: Attribution (CC BY) Document Version Publisher's PDF, also known as Version of record Citation for published version (Harvard): Beger, RD, Dunn, W, Schmidt, MA, Gross, SS, Kirwan, JA, Cascante, M, Brennan, L, Wishart, DS, Oresic, M, Hankemeier, T, Broadhurst, DI, Lane, AN, Suhre, K, Kastenmüller, G, Sumner, SJ, Thiele, I, Fiehn, O & Kaddurah-daouk, R 2016, 'Metabolomics enables precision medicine: “A White Paper, Community Perspective”', Metabolomics, vol. 12, no. 10, 149. https://doi.org/10.1007/s11306-016-1094-6 Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive. If you believe that this is the case for this document, please contact [email protected] providing details and we will remove access to the work immediately and investigate. Download date: 23. Sep. 2021 Metabolomics (2016) 12:149 DOI 10.1007/s11306-016-1094-6 ORIGINAL ARTICLE Metabolomics enables precision medicine: ‘‘A White Paper, Community Perspective’’ 1 2 3 4 Richard D. Beger • Warwick Dunn • Michael A. Schmidt • Steven S. Gross • 5 6,7 8 9 Jennifer A. Kirwan • Marta Cascante • Lorraine Brennan • David S. Wishart • 10 11 12 13 Matej Oresic • Thomas Hankemeier • David I. Broadhurst • Andrew N. Lane • 14 15 16 17 Karsten Suhre • Gabi Kastenmu¨ller • Susan J. Sumner • Ines Thiele • 18,19 20 Oliver Fiehn • Rima Kaddurah-Daouk • for ‘‘Precision Medicine and Pharmacometabolomics Task Group’’-Metabolomics Society Initiative Received: 19 July 2016 / Accepted: 8 August 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract of that individual’s overall health status. This metabolic Introduction: Background to metabolomics Metabolomics state reflects what has been encoded by the genome, and is the comprehensive study of the metabolome, the reper- modified by diet, environmental factors, and the gut toire of biochemicals (or small molecules) present in cells, microbiome. The metabolic profile provides a quantifiable tissues, and body fluids. The study of metabolism at the readout of biochemical state from normal physiology to global or ‘‘-omics’’ level is a rapidly growing field that has diverse pathophysiologies in a manner that is often not the potential to have a profound impact upon medical obvious from gene expression analyses. Today, clinicians practice. At the center of metabolomics, is the concept that capture only a very small part of the information contained a person’s metabolic state provides a close representation in the metabolome, as they routinely measure only a & Rima Kaddurah-Daouk 10 Turku Centre for Biotechnology, University of Turku, Turku, [email protected] Finland 11 Division of Analytical Biosciences and Cluster Systems 1 Division of Systems Biology, National Center for Pharmacology, Leiden Academic Centre for Drug Research, Toxicological Research, U.S. Food and Drug Administration, Leiden University & Netherlands Metabolomics Centre, Jefferson, AR 72079, USA Leiden, The Netherlands 2 School of Biosciences, Phenome Centre Birmingham and 12 School of Science, Edith Cowan University, Perth, Australia Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Edgbaston, 13 Center for Environmental Systems Biochemistry, Department Birmingham B15 2TT, UK Toxicology and Cancer Biology, Markey Cancer Center, Lexington, KY, USA 3 Advanced Pattern Analysis and Countermeasures Group, Research Innovation Center, Colorado State University, 14 Department of Physiology and Biophysics, Weill Cornell Fort Collins, CO 80521, USA Medical College in Qatar, Doha, Qatar 4 Department of Pharmacology, Weill Cornell Medical 15 Institute of Bioinformatics and Systems Biology, Helmholtz College, New York, NY 10021, USA Center Munich, Oberschleißheim, Germany 5 School of Biosciences, University of Birmingham, 16 Discovery Sciences, RTI International, Research Triangle Edgbaston, Birmingham B15 2TT, UK Park, Durham, NC, USA 6 Department of Biochemistry and Molecular Biomedicine, 17 University of Luxembourg, Luxembourg Centre for Systems Faculty of Biology, Universitat de Barcelona, Av Diagonal Biomedicine, Campus Belval, Esch-Sur-Alzette, 643, 08028 Barcelona, Spain Luxembourg 7 Institute of Biomedicine of Universitat de Barcelona (IBUB) 18 West Coast Metabolomics Center, UC Davis, Davis, CA, and CSIC-Associated Unit, Barcelona, Spain USA 8 UCD Institute of Food and Health, UCD, Belfield, Dublin, 19 Biochemistry Department, King Abdulaziz University, Ireland Jeddah, Saudi Arabia 9 Departments of Computing Science and Biological Sciences, University of Alberta, Edmonton, AB, Canada 123 149 Page 2 of 15 Original Article narrow set of blood chemistry analytes to assess health and for variation in responses to treatment, which illustrates how disease states. Examples include measuring glucose to pharmacometabolomics and pharmacogenomics are com- monitor diabetes, measuring cholesterol and high density plementary and powerful tools for precision medicine. lipoprotein/low density lipoprotein ratio to assess cardio- Conclusions: Key scientific concepts and recommendations vascular health, BUN and creatinine for renal disorders, for precision medicine Our metabolomics community and measuring a panel of metabolites to diagnose potential believes that inclusion of metabolomics data in precision inborn errors of metabolism in neonates. medicine initiatives is timely and will provide an extremely Objectives of White Paper—expected treatment outcomes valuable layer of data that compliments and informs other data and metabolomics enabling tool for precision medicine We obtained by these important initiatives. Our Metabolomics anticipate that the narrow range of chemical analyses in Society, through its ‘‘Precision Medicine and Pharma- current use by the medical community today will be replaced cometabolomics Task Group’’, with input from our metabo- in the future by analyses that reveal a far more comprehen- lomics community at large, has developed this White Paper sive metabolic signature. This signature is expected to where we discuss the value and approaches for including describe global biochemical aberrations that reflect patterns metabolomics data in large precision medicine initiatives. of variance in states of wellness, more accurately describe This White Paper offers recommendations for the selection of specific diseases and their progression, and greatly aid in state of-the-art metabolomics platforms and approaches that differential diagnosis. Such future metabolic signatures will: offer the widest biochemical coverage, considers critical (1) provide predictive, prognostic, diagnostic, and surrogate sample collection and preservation, as well as standardization markers of diverse disease states; (2) inform on underlying of measurements, among other important topics. We antici- molecular mechanisms of diseases; (3) allow for sub-clas- pate that our metabolomics community will have represen- sification of diseases, and stratification of patients based on tation in large precision medicine initiatives to provide input metabolic pathways impacted; (4) reveal biomarkers for with regard to sample acquisition/preservation, selection of drug response phenotypes, providing an effective means to optimal omics technologies, and key issues regarding data predict variation in a subject’s response to treatment (phar- collection, interpretation, and dissemination. We strongly macometabolomics); (5) define a metabotype for each recommend the collection and biobanking of samples for specific genotype, offering a functional read-out for genetic precision medicine initiatives that will take into consideration variants: (6) provide a means to monitor response and needs for large-scale metabolic phenotyping studies. recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and Keywords Metabolomics Á Metabonomics
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