Abstract
This chapter is intended to familiarize readers with the field of metabolomics and some of the algorithms, data analysis strategies, and computer programs used to analyze or interpret metabolomic data. Specifically, this chapter provides a brief overview of the experimental approaches and applications of metabolomics followed by a description of the spectral and statistical analysis tools for metabolomics. The chapter concludes with a discussion of the resources that can be used to interpret and analyze metabolomic data at a biological or clinical level. Emerging needs, challenges, and recent progress being made in these areas are also discussed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
German JB, Hammock BD, Watkins SM. (2005) Metabolomics: building on a century of biochemistry to guide human health. Metabolomics 1:3–9.
Wishart DS. (2007) Human Metabolome Database: completing the “human parts list.” Pharmacogenomics 8:683–686.
Yang J, Xu G, Hong Q, Liebich HM, Lutz K, Schmülling RM, Wahl HG. (2004) Discrimination of Type 2 diabetic patients from healthy controls by using metabonomics method based on their serum fatty acid profiles. J Chromatogr B 813:53–58.
Williamson MP, Humm G, Crisp AJ. (1989) 1H nuclear magnetic resonance investigation of synovial fluid components in osteoarthritis, rheumatoid arthritis and traumatic effusions. Br J Rheumatol 28:23–27.
Wishart DS, Querengesser LMM, Lefebvre BA, Epstein NA, Greiner R, Newton JB. (2001) Magnetic resonance diagnostics: a new technology for high-throughput clinical diagnostics. Clin Chemistry 47:1918–1921.
Moolenaar SH, Engelke UF, Wevers RA. (2003) Proton nuclear magnetic resonance spectroscopy of body fluids in the field of inborn errors of metabolism. Ann Clin Biochem 40:16–24.
Coen M, O’Sullivan M, Bubb WA, Kuchel PW, Sorrell T. (2005) Proton nuclear magnetic resonance-based metabonomics for rapid diagnosis of meningitis and ventriculitis. Clin Infect Dis 41:1582–1590.
Griffin JL, Bollard ME. (2004) Metabonomics: its potential as a tool in toxicology for safety assessment and data integration. Curr Drug Metab 5:389–398.
Wishart DS. (2005) Metabolomics: the principles and potential applications to transplantation. Am J Transplant 5:2814–2820.
Wishart DS. (2007) Current progress in computational metabolomics. Brief Bioinform 8:279–293.
Coley NG. (2004) Medical chemists and the origins of clinical chemistry in Britain (circa 1750–1850). Clin Chem 50:961–972.
Rosenfeld L. (2001) Clinical chemistry since 1800: growth and development. Clin Chem 48:186–197.
Tietz NW. (1995) Clinical Guide to Laboratory Tests, 3rd ed., WB Saunders Press, Philadelphia, PA.
Dunn WB, Bailey NJ, Johnson HE. (2005) Measuring the metabolome: current analytical technologies. Analyst 130:606–625.
Cotter D, Maer A, Guda C, Saunders B, Subramaniam S. (2006) LMPD: LIPID MAPS proteome database. Nucleic Acids Res 34(Database issue):D507–510.
Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S, Fung C, Nikolai L, Lewis M, Coutouly MA, Forsythe I, Tang P, Shrivastava S, Jeroncic K, Stothard P, Amegbey G, Block D, Hau DD, Wagner J, Miniaci J, Clements M, Gebremedhin M, Guo N, Zhang Y, Duggan GE, Macinnis GD, Weljie AM, Dowlatabadi R, Bamforth F, Clive D, Greiner R, Li L, Marrie T, Sykes BD, Vogel HJ, Querengesser L. (2007) HMDB: the Human Metabolome Database. Nucleic Acids Res 35(Database issue):D521–526.
Smith CA, O’Maille G, Want EJ, Qin C, Trauger SA, Brandon TR, Custodio DE, Abagyan R, Siuzdak G. (2005) METLIN: a metabolite mass spectral database. Ther Drug Monit 27:747–751.
Saude EJ, Sykes BD. (2007) Urine stability for metabolomic studies: effects of preparation and storage. Metabolomics 3:19–24.
Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC, Nicholson JK. (2007) Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2:2692–2703.
Jiye A, Trygg J, Gullberg J, Johansson AI, Jonsson P, Antti H, Marklund SL, Moritz T. (2005) Extraction and GC/MS analysis of the human blood plasma metabolome. Anal Chem 77:8086–8094.
Schnackenberg LK, Beger RD. (2006) Monitoring the health to disease continuum with global metabolic profiling and systems biology. Pharmacogenomics 7:1077–1086.
German JB, Gillies LA, Smilowitz JT, Zivkovic AM, Watkins SM. (2007) Lipidomics and lipid profiling in metabolomics. Curr Opin Lipidol 18:66–71.
Guo K, Ji C, Li L. (2007) Stable-isotope dimethylation labeling combined with LC-ESI MS for quantification of amine-containing metabolites in biological samples. Anal Chem 79:8631–8638.
Weljie AM, Dowlatabadi R, Miller BJ, Vogel HJ, Jirik FR. (2007) An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spectroscopy. J Proteome Res 6:3456–3464.
van der Werf MJ, Overkamp KM, Muilwijk B, Coulier L, Hankemeier T. (2007) Microbial metabolomics: toward a platform with full metabolome coverage. Anal Biochem 370:17–25.
Trygg J, Holmes E, Lundstedt T. (2007) Chemometrics in metabonomics. J Proteome Res 6:469–479.
Weljie AM, Newton J, Mercier P, Carlson E, Slupsky CM. (2006) Targeted profiling: quantitative analysis of 1H NMR metabolomics data. Anal Chem 78: 4430–4442.
Lavine B, Workman JJ, Jr. (2004) Chemometrics. Anal Chem 76:3365–3371.
Wu W, Daszykowski M, Walczak B, Sweatman BC, Connor SC, Haselden JN, Crowther DJ, Gill RW, Lutz MW. (2006) Peak alignment of urine NMR spectra using fuzzy warping. J Chem Inf Model 46:863–875.
Kind T, Tolstikov V, Fiehn O, Weiss RH. (2007) A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal Biochem 363:185–195.
Ding C, He X. (2004) K-means clustering via principal component analysis. Proc of the International Conference on Machine Learning (ICML 2004), pp. 225–232.
Holmes E, Nicholls AW, Lindon JC, Connor SC, Connelly JC, Haselden JN, Damment SJ, Spraul M, Neidig P, Nicholson JK. (2000) Chemometric models for toxicity classification based on NMR spectra of biofluids. Chem Res Toxicol 13:471–478.
Smith IC, Baert R. (2003) Medical diagnosis by high resolution NMR of human specimens. IUBMB Life 55:273–277.
Wilson ID, Plumb R, Granger J, Major H, Williams R, Lenz EM. (2005) HPLC-MS-based methods for the study of metabonomics. J Chromatogr B 817:67–76.
Molinaro AM, Simon R, Pfeiffer RM. (2005) Prediction error estimation: a comparison of resampling methods. Bioinformatics 21:3301–3307.
Serkova NJ, Rose JC, Epperson LE, Carey HV, Martin SL. (2007) Quantitative analysis of liver metabolites in three stages of the circannual hibernation cycle in 13-lined ground squirrels by NMR. Physiol Genomics 31:15–24.
Niwa T. (1986) Metabolic profiling with gas chromatography-mass spectrometry and its application to clinical medicine. J Chromatogr 379:313–345.
La Marca G, Casetta B, Malvagia S, Pasquini E, Innocenti M, Donati MA, Zammarchi E. (2006) Implementing tandem mass spectrometry as a routine tool for characterizing the complete purine and pyrimidine metabolic profile in urine samples. J Mass Spectrom 41:1442–1452.
Kopka J, Schauer N, Krueger S, Birkemeyer C, Usadel B, Bergmüller E, Dörmann P, Weckwerth W, Gibon Y, Stitt M, Willmitzer L, Fernie AR, Steinhauser D. (2005) GMD@CSB.DB: the Golm Metabolome Database. Bioinformatics 21:1635–1638.
Ulrich EL, Akutsu H, Doreleijers JF, Harano Y, Ioannidis YE, Lin J, Livny M, Mading S, Maziuk D, Miller Z, Nakatani E, Schulte CF, Tolmie DE, Kent Wenger R, Yao H, Markley JL. (2008) BioMagResBank. Nucleic Acids Res 36(Database issue):D402–408.
Rossé G, Neidig P, Schröder H. (2002) Automated structure verification of small molecules libraries using 1D and 2D NMR techniques. Methods Mol Biol 201:123–139.
Kind T, Fiehn O. (2007) Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry. BMC Bioinformatics 8:105.
Jiang H, Somogyi A, Timmermann BN, Gang DR. (2006) Instrument dependence of electrospray ionization and tandem mass spectrometric fragmentation of the gingerols. Rapid Commun Mass Spectrom 20:3089–3100.
Fardet A, Canlet C, Gottardi G, Lyan B, Llorach R, Rémésy C, Mazur A, Paris A, Scalbert A. (2007) Whole-grain and refined wheat flours show distinct metabolic profiles in rats as assessed by a 1H NMR-based metabonomic approach. J Nutr 137:923–929.
Margalit A, Duffin KL, Isakson PC. (1996) Rapid quantitation of a large scope of eicosanoids in two models of inflammation: development of an electrospray and tandem mass spectrometry method and application to biological studies. Anal Biochem 235:73–81.
Castro IA, Barroso LP, Sinnecker P. (2005) Functional foods for coronary heart disease risk reduction: a meta-analysis using a multivariate approach. Am J Clin Nutr 82:32–40.
Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, Katayama T, Kawashima S, Okuda S, Tokimatsu T, Yamanishi Y. (2008) KEGG for linking genomes to life and the environment. Nucleic Acids Res 36(Database issue):D480–484.
Romero P, Wagg J, Green ML, Kaiser D, Krummenacker M, Karp PD. (2005) Computational prediction of human metabolic pathways from the complete human genome. Genome Biol 6:R2.
Vastrik I, D’Eustachio P, Schmidt E, Joshi-Tope G, Gopinath G, Croft D, de Bono B, Gillespie M, Jassal B, Lewis S, Matthews L, Wu G, Birney E, Stein L. (2007) Reactome: a knowledge base of biologic pathways and processes. Genome Biol 8:R39.
Alves R, Antunes F, Salvador A. (2006) Tools for kinetic modeling of biochemical networks. Nat Biotechnol 24:667–672.
Materi W, Wishart DS. (2007) Computational systems biology in drug discovery and development: methods and applications. Drug Discov Today 12:295–303.
Mendes P. (1993) GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems. Comput Appl Biosci 9:563–571.
Kitano H, Funahashi A, Matsuoka Y, Oda K. (2005) Using process diagrams for the graphical representation of biological networks. Nat Biotechnol 23:961–966.
Sauro HM. (1993) SCAMP: a general-purpose simulator and metabolic control analysis program. Comput Appl Biosci 9:441–450.
Shapiro BE, Levchenko A, Meyerowitz EM, Wold BJ, Mjolsness ED. (2003) Cellerator: extending a computer algebra system to include biochemical arrows for signal transduction simulations. Bioinformatics 19:677–678.
Demir O, Aksan Kurnaz I. (2006) An integrated model of glucose and galactose metabolism regulated by the GAL genetic switch. Comput Biol Chem 30:179–192.
Gagneur J, Casari G. (2005) From molecular networks to qualitative cell behavior. FEBS Lett 579:1867–1871.
Joyce AR, Palsson BO. (2007) Toward whole cell modeling and simulation: comprehensive functional genomics through the constraint-based approach. Prog Drug Res 64:267–309.
Kauffman KJ, Prakash P, Edwards JS. (2003) Advances in flux balance analysis. Curr Opin Biotechnol 14:491–496.
Lee JM, Gianchandani EP, Papin JA. (2006) Flux balance analysis in the era of metabolomics. Brief Bioinform 7:140–150.
Oliveira AP, Nielsen J, Forster J. (2005) Modeling Lactococcus lactis using a genome-scale flux model. BMC Microbiol5:39.
Jin YS, Jeffries TW. (2004) Stoichiometric network constraints on xylose metabolism by recombinant Saccharomyces cerevisiae. Metab Eng 6:229–238.
Durmus Tekir S, Cakir T, Ulgen KO. (2006) Analysis of enzymopathies in the human red blood cells by constraint-based stoichiometric modeling approaches. Comput Biol Chem 30:327–338.
Luo RY, Liao S, Tao GY, Li YY, Zeng S, Li YX, Luo Q. (2006) Dynamic analysis of optimality in myocardial energy metabolism under normal and ischemic conditions. Mol Syst Biol 2:2006.0031.
Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, Srivas R, Palsson BØ. (2007) Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci USA 104:1777–1782.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Wishart, D.S. (2010). Computational Approaches to Metabolomics. In: Matthiesen, R. (eds) Bioinformatics Methods in Clinical Research. Methods in Molecular Biology, vol 593. Humana Press. https://doi.org/10.1007/978-1-60327-194-3_14
Download citation
DOI: https://doi.org/10.1007/978-1-60327-194-3_14
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-60327-193-6
Online ISBN: 978-1-60327-194-3
eBook Packages: Springer Protocols