DOCSLIB.ORG

Metabolomics Enables Precision Medicine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Metabolomics Enables Precision Medicine 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
Load more

Recommended publications
  • A Targeted Neurotransmitter Quantification and Nontargeted
    RSC Advances View Article Online PAPER View Journal | View Issue A targeted neurotransmitter quantification and nontargeted metabolic profiling method for Cite this: RSC Adv., 2020, 10,18305 pharmacometabolomics analysis of olanzapine by using UPLC-HRMS† Dan Liu,‡a Zhuoling An,‡b Pengfei Li,b Yanhua Chen,a Ruiping Zhang, a Lihong Liu,*b Jiuming He *a and Zeper Ablizac Neurotransmitters (NTs) are specific endogenous metabolites that act as “messengers” in synaptic transmission and are widely distributed in the central nervous system. Olanzapine (OLZ), a first-line antipsychotic drug, plays a key role in sedation and hypnosis, but, it presents clinical problems with a narrow therapeutic window, large individual differences and serious adverse effects, as well as an unclear mechanism in vivo. Herein, a simultaneous targeted NT quantification and nontargeted metabolomics method was developed and validated for pharmacometabolomics analysis of OLZ by Creative Commons Attribution-NonCommercial 3.0 Unported Licence. using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Considering the low physiological concentrations of NTs, a full MS scan and target selective ion monitoring (tSIM) scan were combined for nontargeted metabolomics and targeted NT quantification, respectively. By using this strategy, NTs at a very low physiological concentration can be accurately detected and quantified in biological samples by tSIM scans. Moreover, simultaneously nontargeted profiling was also achieved by the full
    [Show full text]
  • Metabolomics Profiling and Pathway Analysis of Human Plasma and Urine T Reveal Further Insights Into the Multifactorial Nature of Coronary Artery Disease ⁎ ⁎ Arwa M
    Clinica Chimica Acta 493 (2019) 112–122 Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/cca Metabolomics profiling and pathway analysis of human plasma and urine T reveal further insights into the multifactorial nature of coronary artery disease ⁎ ⁎ Arwa M. Amina,b, ,1, Hamza Mostafaa, ,1, Nor Hayati Arifc, Muhamad Ali SK Abdul Kadera,d, Yuen Kah Haya a School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia b Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al Madinah Al Munawwarah, Saudi Arabia c Psychiatry Department, Hospital Pulau Pinang, Malaysia d Cardiology Department, Hospital Pulau Pinang, Penang, Malaysia ARTICLE INFO ABSTRACT Keywords: Background: Coronary artery disease (CAD) claims lives yearly. Nuclear magnetic resonance (1H NMR) meta- Coronary artery disease bolomics analysis is efficient in identifying metabolic biomarkers which lend credence to diagnosis. Weaimedto 1 H NMR identify CAD metabotypes and its implicated pathways using 1H NMR analysis. Metabolomics Methods: We analysed plasma and urine samples of 50 stable CAD patients and 50 healthy controls using 1H Systems biology NMR. Orthogonal partial least square discriminant analysis (OPLS-DA) followed by multivariate logistic re- Single nucleotide polymorphism gression (MVLR) models were developed to indicate the discriminating metabotypes. Metabolic pathway ana- Gut microbiota lysis was performed to identify the implicated pathways. Results: Both plasma and urine OPLS-DA models had specificity, sensitivity and accuracy of 100%, 96% and 98%, respectively. Plasma MVLR model had specificity, sensitivity, accuracy and AUROC of 92%, 86%, 89%and 0.96, respectively. The MVLR model of urine had specificity, sensitivity, accuracy and AUROC of 90%, 80%, 85% and 0.92, respectively.
    [Show full text]
  • Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway
    Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway Hongjie Zhu1., Mikhail B. Bogdanov2., Stephen H. Boyle1, Wayne Matson3, Swati Sharma3, Samantha Matson3,4, Erik Churchill1, Oliver Fiehn5, John A. Rush6, Ranga R. Krishnan1,6, Eve Pickering7, Marielle Delnomdedieu8, Rima Kaddurah-Daouk1*, Pharmacometabolomics Research Network 1 Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, United States of America, 2 Department of Neurology and Neuroscience Weill Cornell Medical College, New York, New York, United States of America, 3 Department of Systems Biochemistry, Bedford VA Medical Center, Bedford, Massachusetts, United States of America, 4 Massachusetts General Hospital, Boston, Massachusetts, United States of America, 5 Genome Center, University of California Davis, Davis, California, United States of America, 6 Duke-NUS Graduate Medical School, Singapore, Singapore, 7 Pfizer Global R&D, Clinical Research Statistics, Groton, Connecticut, United States of America, 8 Pfizer Global R&D, Neuroscience Clinical Research, Groton, Connecticut, United States of America Abstract Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17).
    [Show full text]
  • Review Article the Use of Omic Technologies Applied to Traditional Chinese Medicine Research
    Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2017, Article ID 6359730, 19 pages https://doi.org/10.1155/2017/6359730 Review Article The Use of Omic Technologies Applied to Traditional Chinese Medicine Research Dalinda Isabel Sánchez-Vidaña,1 Rahim Rajwani,2 and Man-Sau Wong3 1 Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong 2Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong 3Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Correspondence should be addressed to Man-Sau Wong; [email protected] Received 28 July 2016; Revised 23 October 2016; Accepted 24 October 2016; Published 31 January 2017 Academic Editor: Fabio Firenzuoli Copyright © 2017 Dalinda Isabel Sanchez-Vida´ na˜ et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Natural products represent one of the most important reservoirs of structural and chemical diversity for the generation of leads in the drug development process. A growing number of researchers have shown interest in the development of drugs based on Chinese herbs. In this review, the use and potential of omic technologies as powerful tools in the modernization of traditional Chinese medicine are discussed. The analytical combination from each omic approach is crucial for understanding the working mechanisms of cells, tissues, organs, and organisms as well as the mechanisms of disease. Gradually, omic approaches have been introduced in every stage of the drug development process to generate high-quality Chinese medicine-based drugs.
    [Show full text]
  • Important Considerations for Sample Collection in Metabolomics Studies with a Special Focus on Applications to Liver Functions
    H OH metabolites OH Review Important Considerations for Sample Collection in Metabolomics Studies with a Special Focus on Applications to Liver Functions Lorraine Smith 1, Joran Villaret-Cazadamont 1, Sandrine P. Claus 2 ,Cécile Canlet 1, Hervé Guillou 1 , Nicolas J. Cabaton 1 and Sandrine Ellero-Simatos 1,* 1 Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31300 Toulouse, France; [email protected] (L.S.); [email protected] (J.V.-C.); [email protected] (C.C.); [email protected] (H.G.); [email protected] (N.J.C.) 2 LNC Therapeutics, 17 place de la Bourse, 33076 Bordeaux, France; [email protected] * Correspondence: [email protected] Received: 11 February 2020; Accepted: 7 March 2020; Published: 12 March 2020 Abstract: Metabolomics has found numerous applications in the study of liver metabolism in health and disease. Metabolomics studies can be conducted in a variety of biological matrices ranging from easily accessible biofluids such as urine, blood or feces, to organs, tissues or even cells. Sample collection and storage are critical steps for which standard operating procedures must be followed. Inappropriate sample collection or storage can indeed result in high variability, interferences with instrumentation or degradation of metabolites. In this review, we will first highlight important general factors that should be considered when planning sample collection in the study design of metabolomic studies, such as nutritional status and circadian rhythm. Then, we will discuss in more detail the specific procedures that have been described for optimal pre-analytical handling of the most commonly used matrices (urine, blood, feces, tissues and cells).
    [Show full text]
  • S41598-018-25035-1.Pdf
    www.nature.com/scientificreports OPEN An Innovative Approach for The Integration of Proteomics and Metabolomics Data In Severe Received: 23 October 2017 Accepted: 9 April 2018 Septic Shock Patients Stratifed for Published: xx xx xxxx Mortality Alice Cambiaghi1, Ramón Díaz2, Julia Bauzá Martinez2, Antonia Odena2, Laura Brunelli3, Pietro Caironi4,5, Serge Masson3, Giuseppe Baselli1, Giuseppe Ristagno 3, Luciano Gattinoni6, Eliandre de Oliveira2, Roberta Pastorelli3 & Manuela Ferrario 1 In this work, we examined plasma metabolome, proteome and clinical features in patients with severe septic shock enrolled in the multicenter ALBIOS study. The objective was to identify changes in the levels of metabolites involved in septic shock progression and to integrate this information with the variation occurring in proteins and clinical data. Mass spectrometry-based targeted metabolomics and untargeted proteomics allowed us to quantify absolute metabolites concentration and relative proteins abundance. We computed the ratio D7/D1 to take into account their variation from day 1 (D1) to day 7 (D7) after shock diagnosis. Patients were divided into two groups according to 28-day mortality. Three diferent elastic net logistic regression models were built: one on metabolites only, one on metabolites and proteins and one to integrate metabolomics and proteomics data with clinical parameters. Linear discriminant analysis and Partial least squares Discriminant Analysis were also implemented. All the obtained models correctly classifed the observations in the testing set. By looking at the variable importance (VIP) and the selected features, the integration of metabolomics with proteomics data showed the importance of circulating lipids and coagulation cascade in septic shock progression, thus capturing a further layer of biological information complementary to metabolomics information.
    [Show full text]
  • A Metabolomics Approach to Pharmacotherapy Personalization
    Journal of Personalized Medicine Review A Metabolomics Approach to Pharmacotherapy Personalization Elena E. Balashova *, Dmitry L. Maslov and Petr G. Lokhov Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow 119121, Russia; [email protected] (D.L.M.); [email protected] (P.G.L.) * Correspondence: [email protected] Received: 29 June 2018; Accepted: 3 September 2018; Published: 5 September 2018 Abstract: The optimization of drug therapy according to the personal characteristics of patients is a perspective direction in modern medicine. One of the possible ways to achieve such personalization is through the application of “omics” technologies, including current, promising metabolomics methods. This review demonstrates that the analysis of pre-dose metabolite biofluid profiles allows clinicians to predict the effectiveness of a selected drug treatment for a given individual. In the review, it is also shown that the monitoring of post-dose metabolite profiles could allow clinicians to evaluate drug efficiency, the reaction of the host to the treatment, and the outcome of the therapy. A comparative description of pharmacotherapy personalization (pharmacogenomics, pharmacoproteomics, and therapeutic drug monitoring) and personalization based on the analysis of metabolite profiles for biofluids (pharmacometabolomics) is also provided. Keywords: pharmacometabolomics; metabolomics; pharmacogenomics; therapeutic drug monitoring; personalized medicine; mass spectrometry 1. Introduction The uniformity of the drug response or low inter-individual differences in drug response are commonly accepted tenets in the field of medicine. Almost all drugs are prescribed on the basis of this statement. This approach can be described as treatment of the “average patient” by “the average pill” or “one size fits all”. However, clinicians have long observed that the actual effectiveness of the pharmacotherapy may be variable.
    [Show full text]
  • The Metabolomic Paradigm of Pharmacogenomics in Complex
    ics: O om pe ol n b A a c t c e e M s s Cacabelos, Metabolomics 2012, 2:5 Metabolomics: Open Access DOI: 10.4172/2153-0769.1000e119 ISSN: 2153-0769 Editorial Open Access The Metabolomic Paradigm of Pharmacogenomics in Complex Disorders Ramón Cacabelos1,2* 1EuroEspes Biomedical Research Center, Institute for CNS Disorders and Genomic Medicine, EuroEspes Chair of Biotechnology and Genomics, 15165-Bergondo, Corunna, Spain 2President, World Association of Genomic Medicine, Spain Metabolomics represents the networking organization of multiple pathogenic genes usually converge in metabolomic networks leading biochemical pathways leading to a physiological function in living to specific pathogenic cascades responsible for disease phenotypes. organisms. The frontier between health and disease is likely to be the The genomics of the mechanism of action of drugs has so far been result of a fine-tuning equilibrium or disequilibrium, respectively, neglected by the scientific community, and consequently less than 5% between the genomic-transcriptomic-proteomic-metabolomic cascade of FDA-approved drugs, with a pharmacologically-defined mechanism and environmental factors and/or epigenetic phenomena. In recent of action, have been studied in order to evaluate whether mutations times, diverse metabolomic studies have emerged in medical science in the genes encoding receptors or enzymes may affect efficacy and to explain physiological and pathogenic events in several disciplines, safety issues. Pleiotropic genes, involved in multiple pathogenic events,
    [Show full text]
  • Model-Based Integration of Genomics and Metabolomics Reveals SNP Functionality in Mycobacterium Tuberculosis
    Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis Ove Øyåsa,b,1, Sonia Borrellc,d,1, Andrej Traunerc,d,1, Michael Zimmermanne, Julia Feldmannc,d, Thomas Liphardta,b, Sebastien Gagneuxc,d, Jörg Stellinga,b, Uwe Sauere, and Mattia Zampierie,2 aDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; bSIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; cDepartment of Medical Parasitoloy and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; dUniversity of Basel, 4058 Basel, Switzerland; and eInstitute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland Edited by Ralph R. Isberg, Tufts University School of Medicine, Boston, MA, and approved March 2, 2020 (received for review September 12, 2019) Human tuberculosis is caused by members of the Mycobacterium infection of macrophages (29–32). Beyond analyses of individual tuberculosis complex (MTBC) that vary in virulence and transmis- laboratory strains, however, no systematic characterization and sibility. While genome-wide association studies have uncovered comparative analysis of intrinsic metabolic differences across several mutations conferring drug resistance, much less is known human-adapted MTBC clinical strains has been performed. about the factors underlying other bacterial phenotypes. Variation If the metabolic and other phenotypic diversity between in the outcome of tuberculosis infection and diseases has been MTBC strains contributes to and modulates pathogenicity, an attributed primarily to patient and environmental factors, but obvious question is: Which elements of the limited genetic di- recent evidence indicates an additional role for the genetic diver- versity in the MTBC are responsible for phenotypic strain di- sity among MTBC clinical strains.
    [Show full text]
  • M. Tomita T. Nishioka (Eds.) Metabolomics the Frontier of Systems Biology
    M. Tomita T. Nishioka (Eds.) Metabolomics The Frontier of Systems Biology M. Tomita, T. Nishioka (Eds.) Metabolomics The Frontier of Systems Biology With 112 Figures, Including 4 in Color Springer Masaru Tomita, Ph.D. Professor and Director Institute for Advanced Biosciences Keio University Tsuruoka 997-0035, Japan Takaaki Nishioka, Ph.D. Professor Graduate School of Agricuhure Kyoto University Kyoto 606-8502, Japan This book is based on the Japanese original, M. Tomita, T. Nishioka (Eds.), Metabolome Kenkyu no Saizensen, Springer-Verlag Tokyo, 2003. Library of Congress Control Number: 2005928331 ISBN 4-431-25121-9 Springer-Verlag Tokyo Berlin Heidelberg New York This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Springer is a part of Springer Science+Business Media springeronline.com © Springer-Vertag Tokyo 2005 Printed in Japan Typesetting: Camera-ready by the editor. Printing and binding: Nikkei Printing, Japan Printed on acid-free paper Preface The aim of this book is to review metabolomics research.
    [Show full text]
  • Lipidomics and Metabolomics Service Gain Deeper Insights Into Exosomes
    EXOSOMES LIPIDOMICS AND METABOLOMICS SERVICE GAIN DEEPER INSIGHTS INTO EXOSOMES SYSTEMBIO.COM/LIPIDOMICS HIGHLIGHTS What can lipidomics of exosomes tell you? n Discover novel circulating biomarkers Lipids are an important part of cellular physiology, and are increasingly being recognized for their importance in exosome biology as well. Exosomes were recently shown to have the highest lipid- n Learn more about exosome biology to-protein ratio of all classes of extracellular vesicles (1), with lipid content that both differs from n Send us your sample and receive data the parent cell the vesicles are shed from (2) and also changes as exosomes undergo a variety of in 4 - 6 weeks physiological processes (3). These unique lipid profiles can serve as novel circulating biomarkers, and recent evidence suggests that specific lipid species carried by exosomes can also modulate Service Overview the function of recipient cells (4). Whether you’re interested in With so much information revealed by lipid content, lipidomics studies of exosomes are a great way to identify lipid-based biomarkers and for understanding vesicle biogenesis and function (5). circulating biomarker discovery, basic exosome research, or other TUMOR MICROENVIRONMENT exosome-related studies, SBI’s CANCER CELLS CAFs EXOSOMES Exosome Lipidomics & Metabolomics Service helps you quickly and efficiently get the most information from your exosomes. Simply send Exosomes affect metabolism of cancer us your sample or purified exosomes cells A recent study by Zhao, et al, (6) and we’ll send back a report with demonstrated that exosomes from putative identifications, mass/charge patient-derived cancer-associated fibroblasts (CAFs) can reprogram EXOSOME ratios, and differential analysis (if UPTAKE the cellular machinery in cancer requested).
    [Show full text]
  • Mass Spectrometry-Based Applications and Analytical Method Development for Metabolomics
    Drug Research Program Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki Finland MASS SPECTROMETRY-BASED APPLICATIONS AND ANALYTICAL METHOD DEVELOPMENT FOR METABOLOMICS Päivi Pöhö ACADEMIC DISSERTATION To be presented, with the permission of the Faculty of Pharmacy of the University of Helsinki, for public examination in lecture room 1041, Biocenter 2, on 31 January 2020, at 12 noon. Helsinki 2020 ©Päivi Pöhö ISBN 978-951-51-5757-7 (print) ISBN 978-951-51-5758-4 (online) ISSN 2342-3161 (print) ISSN 2342-317X (online) http://ethesis.helsinki.fi Unigrafia, Helsinki, Finland, 2020 Published in DSHealth series ‘Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis’ The Faculty of Pharmacy uses the Urkund system (plagiarism recognition) to examine all doctoral dissertations. Supervisors Professor Risto Kostiainen Drug Research Program Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki Finland Professor Tapio Kotiaho Drug Research Program Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy and Department of Chemistry Faculty of Science University of Helsinki Finland Reviewers Professor Kati Hanhineva Institute of Public Health and Clinical Nutrition Faculty of Health Sciences University of Eastern Finland Kuopio Finland Professor Uwe Karst Institute of Inorganic and Analytical Chemistry University of Münster Münster Germany Opponent Professor Jonas Bergquist Department of Chemistry - BMC Uppsala University Uppsala Sweden 3 ABSTRACT Metabolites are small molecules present in a biological system that have multiple important biological functions. Changes in metabolite levels reflect genetic and environmental alterations and play a role in multiple diseases. Metabolomics is a discipline that aims to analyze all the small molecules in a biological system simultaneously.
    [Show full text]