METABOLIC PROFILING: ITSROLE IN BIOMARKER DISCOVERYAND GENE FUNCTION ANALYSIS

METABOLIC PROFILING: ITS ROLE IN BIOMARKER DISCOVERY AND GENE FUNCTION ANALYSIS

edited by

George G. Harrigan Pharmacia Corporation Chesterfield, MO 63198

U.S.A.

Royston Goodacre Department of Chemistry, UM/Sr, PO Box 88, Manchester, M60 1 QD,

United Kingdom.

~.

" SPRINGER SCIENCE+BUSINESS MEDIA, LLC

Library of Congress CataIoging-in-Publication Data

Metabolie profiling : its role in biomarker discovery and gene function analysis / edited by George G. Harrigan, Royston Goodacre.

p.;cm. Includes bibliographical references and index. ISBN 978-1-4613-5025-5 ISBN 978-1-4615-0333-0 (eBook)

DOI 10.1007/978-1-4615-0333-0

1. Metabolites 2. Metabolie profile tests 3. Biochemical markers 4. Proteomics 5. Genetic regulation.!. Harrigan, George G. 11. Goodacre, Royston.

QP171 .M37752003 612.3'9--dc21

Copyright © 2003 Springer Science+Business Media New York Originally published by Kluwer Academic Publisher in 2003 Softcover reprint of the hardcover 1 st edition 2003

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Printed on acid-free paper.

TO BETH, SEAN AND EVAN andTO ELIZABETH, TAMARA AND PICKLES

Contents

Contributors ix

Preface Xlll

1. IntroductionGeorge G. Harrigan and Royston Goodacre

2. Metabolome And Proteome Profiling For MicrobialCharacterization 9Seetharaman Vaidyanathan and Royston Goodacre

3. Can 18 NMR Derived Metabolic Profiles Contribute ToProteomic Analyses? 39Julian L. Griffin and Elizabeth Sang

4. Application OfMetabonomics In The PharmaceuticalIndustry 69Alan P. Breau and Glenn H. Cantor

5. Metabolic Profiling In Tumors By In Vivo And In VitroNMR Spectroscopy 83Yeun-Li Chung, Marion Stubbs and John R. Griffiths

6. Raman Spectroscopy For Whole Organism And TissueProfiling 95Sarah Clarke and Royston Goodacre

VIII

7. Metabolic Fingerprinting With Fourier TransformInfrared SpectroscopyDavid I. Ellis, George G. Harrigan and Royston Goodacre

8. Metabolomic Analysis With Fourier Transform IonCyclotron Resonance Mass SpectrometryDayan Goodenowe

9. Stable Isotope-Based Dynamic Metabolic Profiling InDisease And HealthLaszlo G. Boros, Marta Cascante and Wai-Nang Paul Lee

10. The Role OfMetabolomics In Systems BiologyJan van der Greef, Eugene Davidov, Elwin Verheij,Jack Vogels, Rob van der Heijden, Aram S. Adourian,Matej Oresic, Edward W. Marple and Stephen Naylor

11. Use OfMetabolomics To Discover Metabolic PatternsAssociated With Human DiseasesOliver Fiehn and Joachim Spranger

12. Bioactive Lipids In Reproductive DiseasesJaideep Chaudhary, Tim Compton and JeffA. Parrott

13. Evolutionary Computation For The Interpretation OfMetabolomic DataRoyston Goodacre and Douglas B. Kell

14. Dynamic Profiling And Canonical ModelingEberhard O. Voit and Jonas Almeida

15. Databases, Data Modeling And SchemasNigel Hardy and Helen Fuell

16. Databases And Visualization ForMetabolomicsX. Jing Li, Olga Brazhnik, Aejaaz Kamal, Dianjing Guo,Christine Lee, Stefan Hoops and Pedro Mendes

17. The Human MetabolomeChris W.W. Beecher

Index

Contents

111

125

141

171

199

217

239

257

277

293

311

321

Contributors

Aram S. Adourian. Beyond Genomics Inc., 40 Bear Hill Road, Waltham,MA 02451, USA

Jonas Almeida. Department of Biometry and Epidemiology and Departmentof Biochemistry and Molecular Biology, Medical University of SouthCarolina, Charleston, SC 29435, USA

Christopher W. W. Beecher. Paradigm Genetics, 108 TW Alexander Dr.,Research Triangle, NC 27709, USA

Laszlo G. Boros. Harbor-UCLA Research and Education Institute, 1124West Carson Street RBI, Torrance, CA 90502, USA

Olga Brazhnik. Virginia Bioinforrnatics Institute, Virginia Tech(0477),1880 Pratt Dr., Blacksburg, VA 24061, USA

Alan P. Breau. Global Drug Metabolism, Pharrnacia Corporation, 4901Searle Parkway, Skokie, IL 60077, USA

Glenn H. Cantor. Investigative Toxicology, Pharrnacia Corporation, 301Henrietta St., Kalamazoo, MI 49007, USA

Marta Cascante. Department of Biochemistry and Molecular Biology,University of Barcelona, Marti/I Franques 1, Barcelona 08028, Catalonia,Spain

x Contributors

Jaideep Chaudhary. Atairgin Technologies, 101 Theory, Irvine, CA 92612,USA

Yeun-Li Chung. Cancer Research UK Biomedical Magnetic ResonanceResearch Group, Department of Biochemistry and Immunology, St.George's Hospital Medical School, London, SWl7 ORE, UK

Sarah Clarke. Institute of Biological Sciences, University of Wales,Aberystwyth, SY23 3DD, UK

Tim Compton. Atairgin Technologies, 101 Theory, Irvine, CA 92612, USA

Eugene Davidov. Beyond Genomics Inc., 40 Bear Hill Road, Waltham, MA02451, USA

David I. Ellis. Institute of Biological Sciences, University of Wales,Aberystwyth, SY23 3DD, UK

Oliver Fiehn. Max-Planck-Institute of Molecular Plant Physiology, 14424PotsdamlGolm, Germany

Helen Fuell. Department of Computer Sciences, University of Wales,Aberystwyth, SY23 3DB, UK.

Royston Goodacre. Department of Chemistry, University of ManchesterInstitute of Science and Technology, PO Box 88, Sackville St.,Manchester, M60 1QD, UK

Dayan Goodenowe. Phenomenome Discoveries Inc., 204-407 DowneyRoad, Saskatoon SK S7N 4L8, Canada

Julian L. Griffin. Division of Biomedical Sciences, Imperial College ofScience, Technology and Medicine, London, SW7 2AZ, UK

John R. Griffiths. Cancer Research UK Biomedical Magnetic ResonanceResearch Group, Department of Biochemistry and Immunology, St.George's Hospital Medical School, London, SW17 ORE, UK

Dianjing Guo. Virginia Bioinformatics Institute, Virginia Tech (0477), 1880Pratt Dr., Blacksburg, VA 24061, USA

Contributors XI

Nigel Hardy. Department of Computer Sciences, University of Wales,Aberystwyth, SY23 3DB, UK

George G. Harrigan. Global HTS, Pharmacia Corporation, 700Chesterfield Parkway, Chesterfield, MO 63198, USA

Stefan Hoops. Virginia Bioinformatics Institute, Virginia Tech (0477), 1880Pratt Dr., Blacksburg, VA 24061, USA

Aejaaz Kamal. Virginia Bioinformatics Institute, Virginia Tech (0477),1880 Pratt Dr., Blacksburg, VA 24061, USA

Douglas B. Kell. Department of Chemistry, University of ManchesterInstitute of Science and Technology, PO Box 88, Sackville St.,Manchester, M60 1QD, UK

Christine Lee. Virginia Bioinformatics Institute, Virginia Tech (0477), 1880Pratt Dr., Blacksburg, VA 24061, USA

Wai-Nang Paul Lee. Harbor-UCLA Research and Education Institute, 1124West Carson Street RBI, Torrance, CA 90502, USA

X. Jing Li. Virginia Bioinformatics Institute, Virginia Tech (0477), 1880Pratt Dr., Blacksburg, VA 24061, USA

Edward W. Marple. Beyond Genomics Inc., 40 Bear Hill Road, Waltham,MA 02451, USA

Pedro Mendes. Virginia Bioinformatics Institute, Virginia Tech (0477),1880 Pratt Dr., Blacksburg, VA 24061, USA

Stephen Naylor. Beyond Genomics Inc., 40 Bear Hill Road, Waltham, MA02451, USA

Matej Oresic. Beyond Genomics Inc., 40 Bear Hill Road, Waltham, MA,02451, USA

Jeff A. Parrott. Atairgin Technologies, 101 Theory, Irvine, CA 92612, USA

Elizabeth Sang. Department of Biochemistry, Oxford University, Oxford,OXI 3QV, UK

xii Contributors

Joachim Spranger. Gennan Instiute of Human Nutrition (DitE), 14558Bergholz-Rehbriicke, Gennany

Marion Stubbs. Cancer Research UK Biomedical Magnetic ResonanceResearch Group, Department of Biochemistry and Immunology, St.George's Hospital Medical School, London, SWI7 ORE, UK

Seetharaman Vaidyanathan. Instiute of Biological Sciences, University ofWales, Aberystwyth, SY23 3DD, UK

Jan van der Greef. Beyond Genomics Inc., 40 Bear Hill Road, Waltham,MA 02451, USA, TNO Phanna, PO Box 22152031 CE, Zemikedreff 9,2333 CK, Leiden, Netherlands and Leiden University/Amsterdam Centerfor Drug Research, Division of Analytical Sciences, NL-2300 RA Leiden,Netherlands

Rob van der Heijden. Leiden University/Amsterdam Center for DrugResearch, Division of Analytical Sciences, NL-2300 RA Leiden,Netherlands

Elwin Verheij. TNO Phanna, PO Box 22152031 CE, Zemikedreff9, 2333CK, Leiden, Netherlands

Jack Vogels. TNO Phanna, PO Box 2215 2031 CE, Zemikedreff 9, 2333CK, Leiden, Netherlands

Eberhard O. Voit. Department of Biometry and Epidemiology, MedicalUniversity of South Carolina, Charleston, SC 29435, USA

Preface

An impressive amount of data has emerged from genomics andproteomics ventures yet this has often served more to highlight thecomplexity of cellular regulation than to elucidate mechanism. It is alsoevident that biochemical control is not strictly hierarchical and thatintermediary metabolism can contribute to control of regulatory pathways.Metabolic studies are therefore increasingly contributing to gene functionanalyses, and an increased interest in metabolites as biomarkers for diseaseprogression or response to therapeutic intervention is also evident in thepharmaceutical industry. Front Line Strategic Consulting recently stated(September, 2002) that, worldwide, the metabolomics industry is anticipatedto grow at a compound rate of over 40% over the next five years and thatthe market for metabolomic technology sales will exceed $255 million by2007.The purpose of this book is to offer guidelines as to the technology

currently available for such pursuits and the bioinformatics and databasestrategies now being developed. We present evidence that metabolicprofiling is a valuable addition to genomics and proteomics strategiesdevoted to drug discovery and development, and believe that metabolicprofiling may be seen to offer numerous advantages, as will be highlighted inthis volume.There has been a number of recent literature reviews devoted to metabolic

profiling and an increasing number of related conferences, including the FirstInternational Congress of Plant Metabolomics (Wageningen, 2002) and theSysteomics Conference (San Francisco, 2002). The genesis of this book canbe traced to the First Annual Cambridge HealthTech Institute Conference onMetabolic Profiling (Chapel Hill, 2001) and a subsequent conference report

XIV Preface

published in Drug Discovery Today. There has, however, been no definitivevolume that describes progress in this area, particularly in the health carearena, and this book aims to address this. It is not, however, intended as acomplete review of all that is going on in pharmaceutically directedmetabolic profiling. We have not addressed in silico modeling, for example,and of course there has already been several excellent volumes on metaboliccontrol/regulation and the technological impact thereof.We hope that the book will be of interest to researchers in the

pharmaceutical industries (Big Pharma and small venture capital endeavors),academe-industry technology transfer organizations and academicresearchers. The bias of the book is to healthcare and the pharmaceuticalindustry but metabolic profiling has been extensively applied in theagriculture and microbiological arenas. Some of the book contributors havedeveloped their expertise in these areas and have much to offer ourcolleagues in biomedicine. We are of course greatly indebted to ourcontributors without whom this volume would not have been possible. Theyhave succeeded in ensuring a volume of high scientific merit and quality.Finally, we would like to acknowledge our colleagues who contributed

valuable comments and support, and helped in proofreading. RoxanneLaPlante and Elizabeth Coliantes diligently proofread many chapters andhelped with manuscript preparation. They, along with Margann Wideman,Ying Ping Zhang, Nancy Wall and Gilles Goetz, have made valuablecontributions to the development of metabolic profiling at Pharmacia. Wealso thank David Lester for valuable suggestions at the onset of this book.We would like to thank the University of Wales, Aberystwyth and the UKBBSRC and UK EPSRC for allowing us the academic freedom and financialassistance to investigate metabolic profiling, and look forward to continuingthis research in the University of Manchester Institute of Science andTechnology (UMIST).

George G. Harrigan

Royston Goodacre