title: Metabolomics enables precision medicine: "A White Paper, Community Perspective".
abstract: Metabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or "-omics" level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person's metabolic state provides a close representation of that individual's overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates.
  We anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and stratification of patients based on metabolic pathways impacted; (4) reveal biomarkers for drug response phenotypes, providing an effective means to predict variation in a subject's response to treatment (pharmacometabolomics); (5) define a metabotype for each specific genotype, offering a functional read-out for genetic variants: (6) provide a means to monitor response and recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and extreme environments. Importantly, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to measure thousands of metabolites in blood, other body fluids, and tissues. Such tools also enable more robust analysis of response to treatment. New insights have been gained about mechanisms of diseases, including neuropsychiatric disorders, cardiovascular disease, cancers, diabetes and a range of pathologies. A series of ground breaking studies supported by National Institute of Health (NIH) through the Pharmacometabolomics Research Network and its partnership with the Pharmacogenomics Research Network illustrate how a patient's metabotype at baseline, prior to treatment, during treatment, and post-treatment, can inform about treatment outcomes and variations in responsiveness to drugs (e.g., statins, antidepressants, antihypertensives and antiplatelet therapies). These studies along with several others also exemplify how metabolomics data can complement and inform genetic data in defining ethnic, sex, and gender basis for variation in responses to treatment, which illustrates how pharmacometabolomics and pharmacogenomics are complementary and powerful tools for precision medicine.
  Our metabolomics community believes that inclusion of metabolomics data in precision medicine initiatives is timely and will provide an extremely valuable layer of data that compliments and informs other data obtained by these important initiatives. Our Metabolomics Society, through its "Precision Medicine and Pharmacometabolomics Task Group", with input from our metabolomics community at large, has developed this White Paper where we discuss the value and approaches for including metabolomics data in large precision medicine initiatives. This White Paper offers recommendations for the selection of state of-the-art metabolomics platforms and approaches that offer the widest biochemical coverage, considers critical sample collection and preservation, as well as standardization of measurements, among other important topics. We anticipate that our metabolomics community will have representation in large precision medicine initiatives to provide input with regard to sample acquisition/preservation, selection of optimal omics technologies, and key issues regarding data collection, interpretation, and dissemination. We strongly recommend the collection and biobanking of samples for precision medicine initiatives that will take into consideration needs for large-scale metabolic phenotyping studies.
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Beger
authors.affiliation: School of Biosciences, Phenome Centre Birmingham and Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Edgbaston, Birmingham, B15 2TT UK.
authors.forename: Warwick
authors.initials: W
authors.lastname: Dunn
authors.affiliation: Advanced Pattern Analysis and Countermeasures Group, Research Innovation Center, Colorado State University, Fort Collins, CO 80521 USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schmidt
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, NY 10021 USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Gross
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kirwan
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028 Barcelona, Spain ; Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
authors.affiliation: UCD Institute of Food and Health, UCD, Belfield, Dublin Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
authors.affiliation: Departments of Computing Science and Biological Sciences, University of Alberta, Edmonton, AB Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Wishart
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.affiliation: Division of Analytical Biosciences and Cluster Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University & Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.affiliation: School of Science, Edith Cowan University, Perth, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Broadhurst
authors.affiliation: Center for Environmental Systems Biochemistry, Department Toxicology and Cancer Biology, Markey Cancer Center, Lexington, KY USA.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Lane
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Center Munich, Oberschleißheim, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Discovery Sciences, RTI International, Research Triangle Park, Durham, NC USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Sumner
authors.affiliation: University of Luxembourg, Luxembourg Centre for Systems Biomedicine, Campus Belval, Esch-Sur-Alzette, Luxembourg.
authors.forename: Ines
authors.initials: I
authors.lastname: Thiele
authors.affiliation: West Coast Metabolomics Center, UC Davis, Davis, CA USA ; Biochemistry Department, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
authors.affiliation: Psychiatry and Behavioral Sciences, Duke Internal Medicine and Duke Institute for Brain Sciences and Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Box 3903, Durham, NC 27710 USA.
authors.forename: Rima
authors.initials: R
authors.lastname: Kaddurah-Daouk
keywords: Metabolomics; Metabonomics; Personalized medicine; Pharmacometabolomics; Pharmacometabonomics; Precision medicine