From exogenous to endogenous: The inevitable imprint of mass spectrometry in metabolomics

Journal of Proteome Research

Volumn 6, Issue 2, 2007, Pages 459-468

  Want, Elizabeth J ^a   Nordström, Anders ^a   Morita, Hirotoshi ^a   Siuzdak, Gary ^a  

^a Scripps Center for Mass Spectrometry   (United States)

Author keywords

Biomarker characterization; Liquid chromatography; Mass spectrometry; Metabolite database; Metabolomics

Indexed keywords

BIOLOGICAL MARKER;

DATA ANALYSIS; DATA BASE; HUMAN; INFORMATION PROCESSING; IONIZATION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLITE; METABOLOMICS; NONHUMAN; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; REPRODUCIBILITY; REVIEW;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, LIQUID; MASS SPECTROMETRY; METABOLISM; PROTEINS; PROTEOME;

EID: 33847377098     PISSN: 15353893     EISSN: None     Source Type: Journal    
DOI: 10.1021/pr060505+     Document Type: Review

References (120)

1. Dear, G. J.; Ayrton, J.; Plumb, R.; Fraser, I. J. The rapid identification of drug metabolites using capillary liquid chromatography coupled to an ion trap mass spectrometer. Rapid Commun. Mass Spectrom. 1999, 13 (5), 456-463.
2. Zhang, N. Y.; Fountain, S. T.; Bi, H. G.; Rossi, D. T. Quantification and rapid metabolite identification in drug discovery using API time-of-flight LC/MS. Anal. Chem. 2000, 72 (4), 800-806.
3. Shockcor, J. P.; Holmes, E. Metabonomic applications in toxicity screening and disease diagnosis. Curr. Top. Med. Chem. 2002, 2 (1), 35-51.
4. Tiller, P. R.; Romanyshyn, L. A. Liquid chromatography/tandem mass spectrometric quantification with metabolite screening as a strategy to enhance the early drug discovery process. Rapid Commun. Mass Spectrom. 2002, 16 (12), 1225-1231.
5. Plumb, R. S.; Stumpf, C. L.; Granger, J. H.; Castro-Perez, J.; Haselden, J. N.; Dear, G. J. Use of liquid chromatography/time-of-flight mass spectrometry and multivariate statistical analysis shows promise for the detection of drug metabolites in biological fluids. Rapid Commun. Mass Spectrom. 2003, 17 (23), 2632-2638.
6. Deng, Y. Z.; Wu, J. T.; Zhang, H. W.; Olah, T. V. Quantitation of drug metabolites in the absence of pure metabolite standards by high-performance liquid chromatography coupled with a chemiluminescence nitrogen detector and mass spectrometer. Rapid Commun. Mass Spectrom. 2004, 18 (15), 1681-1685.
7. Maurer, H. H. Advances in analytical toxicology: the current role of liquid chromatography-mass spectrometry in drug quantification in blood and oral fluid. Anal. Bioanal. Chem. 2005, 381 (1), 110-118.
8. Staack, R. F.; Varesio, E.; Hopfgartner, G. The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites. Rapid Commun. Mass Spectrom. 2005, 19 (5), 618-626.
9. Liu, D. Q.; Hop, C. E. C. A. Strategies for characterization of drug metabolites using liquid chromatography-tandem mass spectrometry in conjunction with chemical derivatization and on-line H/D exchange approaches. J. Pharm. Biomed. Anal. 2005, 37 (1), 1-18.
10. Cravatt, B. F.; Prosperogarcia, O.; Siuzdak, G.; Gilula, N. B.; Henriksen, S. J.; Boger, D. L.; Lerner, R. A. Chemical Characterization of a Family of Brain Lipids That Induce Sleep. Science 1995, 268 (5216), 1506-1509.
11. Saghatelian, A.; Trauger, S. A.; Want, E. J.; Hawkins, E. G.; Siuzdak, G.; Cravatt, B. F. Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry 2004, 43 (45), 14332-14339.
12. Pauling, L.; Robinson, A. B.; Teranishi, R.; Cary, P. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc. Natl. Acad. Sci. U.S.A. 1971, 68 (10), 2374-2376.
13. Dirren, H.; Robinson, A. B.; Pauling, L. Sex-related patterns in the profiles of human urinary amino acids. Clin. Chem. 1975, 21 (13), 1970-5.
14. Chace, D. H. Mass spectrometry in the clinical laboratory. Chem. Rev. 2001, 101 (2), 445-477.
15. Bino, R. J.; Hall, R. D.; Fiehn, O.; Kopka, J.; Saito, K.; Draper, J.; Nikolau, B. J.; Mendes, P.; Roessner-Tunali, U.; Beale, M. H.; Trethewey, R. N.; Lange, B. M.; Wurtele, E. S.; Sumner, L. W. Potential of metabolomics as a functional genomics tool. Trends Plant Sci. 2004, 9 (9), 418-425.
16. Lindon, J. C.; Nicholson, J. K.; Holmes, E.; Antti, H.; Bollard, M. E.; Keun, H.; Beckonert, O.; Ebbels, T. M.; Reilly, M. D.; Robertson, D.; Stevens, G. J.; Luke, P.; Breau, A. P.; Cantor, G. H.; Bible, R. H.; Niederhauser, U.; Senn, H.; Schlotterbeck, G.; Sidelmann, U. G.; Laursen, S. M.; Tymiak, A.; Car, B. D.; Lehman-McKeeman, L.; Colet, J. M.; Loukaci, A.; Thomas, C. Contemporary issues in toxicology - The role of metabonomics in toxicology and its evaluation by the COMET project. Toxicol. Appl. Pharmacol. 2003, 187 (3), 137-146.
17. Nicholson, J. K.; Connelly, J.; Lindon, J. C.; Holmes, E. Metabonomics: a platform for studying drug toxicity and gene function. Nat. Rev. Drug Discovery 2002, 1 (2), 153-161.
18. Bligny, R.; Douce, R. NMR and plant metabolism. Curr. Opin. Plant Biol. 2001, 4 (3), 191-196.
19. Ratcliffe, R. G.; Shachar-Hill, Y. Probing plant metabolism with NMR. Annu. Rev. Plant Physiol. Plant Mol. Biol. 2001, 52, 499-526.
20. Griffin, J. L.; Williams, H. J.; Sang, E.; Clarke, K.; Rae, C.; Nicholson, J. K. Metabolic profiling of genetic disorders: A multitissue H-1 nuclear magnetic resonance spectroscopic and pattern recognition study into dystrophic tissue. Anal. Biochem. 2001, 293 (1), 16-21.
21. Holmes, E.; Tsang, T. M.; Tabrizi, S. J. The application of NMR-based metabonomics in neurological disorders. NeuroRx 2006, 3 (3), 358-372.
22. Bollard, M. E.; Keun, H. C.; Beckonert, O.; Ebbels, T. M. D.; Antti, H.; Nicholls, A. W.; Shockcor, J. P.; Cantor, G. H.; Stevens, G.; Lindon, J. C.; Holmes, E.; Nicholson, J. K. Comparative metabonomics of differential hydrazine toxicity in the rat and mouse. Toxicol. Appl. Pharmacol. 2005, 204 (2), 135-151.
23. Lenz, E. M.; Bright, J.; Knight, R.; Westwood, F. R.; Davies, D.; Major, H.; Wilson, I. D. Metabonomics with H-1-NMR spectroscopy and liquid chromatography-mass spectrometry applied to the investigation of metabolic changes caused by gentamicin-induced nephrotoxicity in the rat. Biomarkers 2005, 10 (2-3), 173-187.
24. Craig, A.; Sidaway, J.; Holmes, E.; Orton, T.; Jackson, D.; Rowlinson, R.; Nickson, J.; Tonge, R.; Wilson, I.; Nicholson, J. Systems toxicology: Integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat. J. Proteome Res. 2006, 5 (7), 1586-1601.
25. Fiehn, O.; Kopka, J.; Dormann, P.; Altmann, T.; Trethewey, R. N.; Willmitzer, L. Metabolite profiling for plant functional genomics. Nat. Biotechnol. 2000, 18 (11), 1157-1161.
26. Schauer, N.; Fernie, A. R. Plant metabolomics: towards biological function and mechanism. Trends Plant Sci. 2006, in press.
27. Roessner, U.; Wagner, C.; Kopka, J.; Trethewey, R. N.; Willmitzer, L. Technical advance: simultaneous analysis of metabolites in potato tuber by gas chromatography-mass spectrometry. Plant J. 2000, 23 (1), 131-142.
28. Jonsson, P.; Gullberg, J.; Nordstrom, A.; Kusano, M.; Kowalczyk, M,; Sjostrom, M.; Moritz, T. A strategy for identifying differences in large series of metabolomic samples analyzed by GC/MS. Anal. Chem. 2004, 76 (6), 1738-1745.
29. Matuszewski, B. K.; Constanzer, M. L.; Chavez-Eng, C. M. Matrix effect in quantitative LC/MS/MS analyses of biological fluids: a method for determination of finasteride in human plasma at picogram per milliliter concentrations. Anal. Chem. 1998, 70 (5), 882-889.
30. Gangl, E. T.; Annan, M. M.; Spooner, N.; Vouros, P. Reduction of signal suppression effects in ESI-MS using a nanosplitting device. Anal. Chem. 2001, 73 (23), 5635-5644.
31. Gustavsson, S. A.; Samskog, J.; Markides, K. E.; Langstrom, B. Studies of signal suppression in liquid chromatography-electrospray ionization mass spectrometry using volatile ion-pairing reagents. J. Chromatogr. A 2001, 937 (1-2), 41-47.
32. Plumb, R.; Castro-Perez, J.; Granger, J.; Beattie, I.; Joncour, K.; Wright, A. Ultra-performance liquid chromatography coupled to quadrupole-orthogonal time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2004, 18 (19), 2331-2337.
33. Bremer, H. J. Disturbances of Amino Acid Metabolism; Urban & Schwarzenberg: Baltimore, MD, 1981.
34. Hommes, F. A. Techniques in Diagnostic Human Biochemical Genetics: A Laboratory Manual; Wiley-Liss: New York, 1991.
35. Niwa, T. Procedures for MS analysis of clinically relevant compounds. Clin. Chim. Acta 1995, 241-242, 75-152.
36. Idborg, H.; Zamani, L.; Edlund, P. O.; Schuppe-Koistinen, I.; Jacobsson, S. P. Metabolic fingerprinting of rat urine by LC/MS Part 1. Analysis by hydrophilic interaction liquid chromatography-electrospray ionization mass spectrometry. J. Chromatogr., B: Analyt. Technol Biomed. Life Sci. 2005, 828 (1-2), 9-13.
37. Delinsky, A. D.; Delinsky, D. C.; Muralidhara, S.; Fisher, J. W.; Bruckner, J. V.; Bartlett, M. G. Analysis of dichloroacetic acid in rat blood and tissues by hydrophilic interaction liquid chromatography with tandem mass spectrometry. Rapid Commun. Mass Spectrom. 2005, 19 (8), 1075-1083.
38. Tolstikov, V. V.; Fiehn, O. Analysis of highly polar compounds of plant origin: combination of hydrophilic interaction chromatography and electrospray ion trap mass spectrometry. Anal. Biochem. 2002, 301 (2), 298-307.
39. Pisano, R.; Breda, M.; Grassi, S.; James, C. A. Hydrophilic interaction liquid chromatography-APCI-mass spectrometry determination of 5-fluorouracil in plasma and tissues. J. Pharm. Biomed. Anal. 2005, 38 (4), 738-745.
40. Wilson, I. D.; Nicholson, J. K.; Castro-Perez, J.; Granger, J. H.; Johnson, K. A.; Smith, B. W.; Plumb, R. S. High resolution "ultra performance" liquid chromatography coupled to oa-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies. J. Proteome Res. 2005, 4 (2), 591-598.
41. Swartz, M. E.; Murphy, B. J. Ultr performance liquid chromatography: tomorrow's HPLC technology today. Labplus Int. 2004, 18 (3), 6-9.
42. Wilson, I. D.; Plumb, R.; Granger, J.; Major, H.; Williams, R.; Lenz, E. M. HPLC-MS-based methods for the study of metabonomics. J. Chromatogr., B: Analyt. Technol. Biomed. Life Sci. 2005, 817 (1), 67-76.
43. Nordstrom, A.; O'Maille, G.; Qin, C.; Siuzdak, G. Nonlinear data alignment for UPLC-MS and HPLC-MS based metabolomics: quantitative analysis of endogenous and exogenous metabolites in human serum. Anal. Chem. 2006, 78 (10), 3289-3295.
44. Yang, Z. Online hyphenated liquid chromatography-nuclear magnetic resonance spectroscopy-mass spectrometry for drug metabolite and nature product analysis. J. Pharm. Biomed. Anal. 2006, 40 (3), 516-527.
45. Dachtler, M.; Glaser, T.; Kohler, K.; Albert, K. Combined HPLC-MS and HPLC-NMR on-line coupling for the separation and determination of lutein and zeaxanthin stereoisomers in spinach and in retina. Anal. Chem. 2001, 73 (3), 667-674.
46. Srebalus, B.; Hilderbrand, A. E.; Valentine, S. J.; Clemmer, D. E. Resolving isomeric peptide mixtures: a combined HPLC/ion mobility-TOFMS analysis of a 4000-component combinatorial library. Anal. Chem. 2002, 74 (1), 26-36.
47. Boernsen, K. O.; Gatzek, S.; Imbert, G. Controlled protein precipitation in combination with chip-based nanospray infusion mass spectrometry. An approach for metabolomics profiling of plasma. Anal. Chem. 2005, 77 (22), 7255-7264.
48. Wang, G.; Hsieh, Y.; Cui, X.; Cheng, K. C.; Korfmacher, W. A. Ultraperformance liquid chromatography/tandem mass spectrometric determination of testosterone and its metabolites in in vitro samples. Rapid Commun. Mass Spectrom. 2006, 20 (14), 2215-2221.
49. Chace, D. H.; Millington, D. S.; Terada, N.; Kahler, S. G.; Roe, C. R.; Hofman, L. F. Rapid diagnosis of phenylketonuria by quantitative analysis for phenylalanine and tyrosine in neonatal blood spots by tandem mass spectrometry. Clin. Chem. 1993, 39 (1), 66-71.
50. Levy, H. L. Newborn screening by tandem mass spectrometry: a new era. Clin. Chem. 1998, 44 (12), 2401-2402.
51. Chelius, D.; Zhang, T.; Wang, G.; Shen, R. F. Global protein identification and quantification technology using two-dimensional liquid chromatography nanospray mass spectrometry. Anal. Chem. 2003, 75 (23), 6658-6665.
52. Nagele, E.; Vollmer, M.; Horth, P. Two-dimensional nano-liquid chromatography-mass spectrometry system for applications in proteomics. J. Chromatogr. A 2003, 1009 (1-2), 197-205.
53. Chatman, K.; Hollenbeck, T.; Hagey, L.; Vallee, M.; Purdy, R.; Weiss, F.; Siuzdak, G. Nanoelectrospray mass spectrometry and precursor ion monitoring for quantitative steroid analysis and attomole sensitivity. Anal. Chem. 1999, 71 (13), 2358-2363.
54. Griffiths, W. J.; Liu, S.; Yang, Y.; Purdy, R. H.; Sjovall, J. Nano-electrospray tandem mass spectrometry for the analysis of neurosteroid sulphates. Rapid Commun. Mass Spectrom. 1999, 13 (15), 1595-1610.
55. Abian, J.; Oosterkamp, A. J.; Gelpí, E. Comparison of conventional, narrow-bore and capillary liquid chromatography/mass spectrometry for electrospray ionization mass spectrometry: practical considerations. J. Mass Spectrom. 1999, 34 (4), 244-254.
56. Keski-Hynnila, H.; Kurkela, M.; Elovaara, E.; Antonio, L.; Magdalou, J.; Luukkanen, L.; Taskinen, J.; Kostiainen, R. Comparison of electrospray, atmospheric pressure chemical ionization, and atmospheric pressure photoionization in the identification of apomorphine, dobutamine, and entacapone phase II metabolites in biological samples. Anal. Chem. 2002, 74 (14), 3449-3457.
57. Raffaelli, A.; Saba, A. Atmospheric pressure photoionization mass spectrometry. Mass Spectrom. Rev. 2003, 22 (5), 318-331.
58. Kratzsch, C.; Tenberken, O.; Peters, F. T.; Weber, A. A.; Kraemer, T.; Maurer, H. H. Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization. J. Mass Spectrom. 2004, 39 (8), 856-872.
59. Byrdwell, W. C. Atmospheric pressure chemical ionization mass spectrometry for analysis of lipids. Lipids 2001, 36 (4), 327-346.
60. De Marchi, N.; De Petrocellis, L.; Orlando, P.; Daniele, F.; Fezza, F.; Di Marzo, V. Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis. 2003, 2, 5.
61. Dally, J. E.; Gorniak, J.; Bowie, R.; Bentzley, C. M. Quantitation of underivatized free amino acids in mammalian cell culture media using matrix assisted laser desorption ionization time-of-flight mass spectrometry. Anal. Chem. 2003, 75 (19), 5046-5053.
62. Edwards, J. L.; Kennedy, R. T. Metabolomic analysis of eukaryotic tissue and prokaryotes using negative mode MALDI time-of-flight mass spectrometry. Anal. Chem. 2005, 77 (7), 2201-2209.
63. Vaidyanathan, S.; Gaskell, S.; Goodacre, R. Matrix-suppressed laser desorption/ionisation mass spectrometry and its suitability for metabolome analyses. Rapid Commun. Mass Spectrom. 2006, 20 (8), 1192-1198.
64. Shen, Z.; Thomas, J. J.; Averbuj, C.; Broo, K. M.; Engelhard, M.; Crowell, J. E.; Finn, M. G.; Siuzdak, G. Porous silicon as a versatile platform for laser desorption/ionization mass spectrometry. Anal. Chem. 2001, 73 (3), 612-619.
65. Vaidyanathan, S.; Jones, D.; Broadhurst, D. I.; Ellis, J.; Jenkins, T.; Dunn, W. B.; Hayes, A.; Burton, N.; Oliver, S. G.; Kell, D. B.; Goodacre, R. A laser desorption ionisation mass spectrometry approach for high throughput metabolomics. Metabolomics 2005, 1 (3), 243-250.
66. Chen, H.; Pan, Z.; Talaty, N.; Raftery, D.; Cooks, R. G. Combining desorption electrospray ionization mass spectrometry and nuclear magnetic resonance for differential metabolomics without sample preparation. Rapid Commun. Mass Spectrom. 2006, 20 (10), 1577-1584.
67. Corcoran, O.; Spraul, M. LC-NMR-MS in drug discovery. Drug Discovery Today 2003, 8 (14), 624-631.
68. Crockford, D. J.; Holmes, E.; Lindon, J. C.; Plumb, R. S.; Zirah, S.; Bruce, S. J.; Rainville, P.; Stumpf, C. L.; Nicholson, J. K. Statistical heterospectroscopy, an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies. Anal. Chem. 2006, 78 (2), 363-371.
69. Patrie, S. M.; Charlebois, J. P.; Whipple, D.; Kelleher, N. L.; Hendrickson, C. L.; Quinn, J. P.; Marshall, A. G.; Mukhopadhyay, B. Construction of a hybrid quadrupole/Fourier transform ion cyclotron resonance mass spectrometer for versatile MS/MS above 10 kDa. J. Am. Soc. Mass Spectrom. 2004, 15 (7), 1099-1108.
70. Katajamaa, M.; Oresic, M. Processing methods for differential analysis of LC/MS profile data. BMC Bioinformatics 2005, 6, 179.
71. Katajamaa, M.; Miettinen, J.; Oresic, M. MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data. Bioinformatics 2006, 22 (5), 634-636.
72. Smith, C. A.; Want, E. J.; O'Maille, G.; Abagyan, R.; Siuzdak, G. XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal. Chem. 2006, 78 (3), 779-787.
73. Broeckling, C. D.; Reddy, I. R.; Duran, A. L.; Zhao, X.; Sumner, L. W. MET-IDEA: data extraction tool for mass spectrometry-based metabolomics. Anal. Chem. 2006, 78 (13), 4334-4341.
74. Hastings, C. A.; Norton, S. M.; Roy, S. New algorithms for processing and peak detection in liquid chromatography/mass spectrometry data. Rapid Commun. Mass Spectrom. 2002, 16 (5), 462-467.
75. Floter, A.; Nicolas, J.; Schaub, T.; Selbig, J. Threshold extraction in metabolite concentration data. Bioinformatics 2004, 20 (10), 1491-1494.
76. Norton, S. M.; Huyn, P.; Hastings, C. A.; Heller, J. C. Data mining of spectroscopic data for biomarker discovery. Curr. Opin. Drug Discov. Devel. 2001, 4 (3), 325-331.
77. Idborg, H.; Edlund, P. O.; Jacobsson, S. P. Multivariate approaches for efficient detection of potential metabolites from liquid chromatography/mass spectrometry data. Rapid Commun. Mass Spectrom. 2004, 18 (9), 944-954.
78. Lutz, U.; Lutz, R. W.; Lutz, W. K. Metabolic profiling of glucuronides in human urine by LC-MS/MS and partial least-squares discriminant analysis for classification and prediction of gender. Anal. Chem. 2006, 78 (13), 4564-4571.
79. Jolliffe, I. T. Principal Component Analysis, 2nd ed.; Springer: New York, 2002.
80. Taylor, J.; King, R. D.; Altmann, T.; Fiehn, O. Application of metabolomics to plant genotype discrimination using statistics and machine learning. Bioinformatics 2002, 18 Suppl 2, S241-248.
81. Choi, H. K.; Choi, Y. H.; Verberne, M.; Lefeber, A. W.; Erkelens, C.; Verpoorte, R. Metabolic fingerprinting of wild type and transgenic tobacco plants by 1H NMR and multivariate analysis technique. Phytochemistry 2004, 65 (7), 857-864.
82. Yeung, K. Y.; Ruzzo, W. L. Principal component analysis for clustering gene expression data. Bioinformatics 2001, 17 (9), 763-774.
83. Martens, H.; Naes, T. Multivariate Calibration; John Wiley & Sons Inc.: New York, 1989.
84. Malinowski, E. R. Factor Analysis in Chemistry, Wiley-Interscience: New York, 1991.
85. Dwek, M. V.; Alaiya, A. A. Proteome analysis enables separate clustering of normal breast, benign breast and breast cancer tissues. Br. J. Cancer 2003, 89 (2), 305-307.
86. Trygg, J.; Wold, S. Orthogonal projections to latent structures (O-PLS). J. Chemom. 2002, 16 (3), 119-128.
87. Trygg, J. O2-PLS for qualitative and quantitative analysis in multivariate calibration. J. Chemom. 2002, 16 (6), 283-293.
88. Cloarec, O.; Dumas, M. E.; Craig, A.; Barton, R. H.; Trygg, J.; Hudson, J.; Blancher, C.; Gauguier, D.; Lindon, J. C.; Holmes, E.; Nicholson, J. Statistical total correlation spectroscopy: an exploratory approach for latent biomarker identification from metabolic 1H NMR data sets. Anal. Chem. 2005, 77 (5), 1282-1289.
89. Gaweda, A. E.; Jacobs, A. A.; Brier, M. E.; Zurada, J. M. Pharmacodynamic population analysis in chronic renal failure using artificial neural networks - a comparative study. Neural Netw. 2003, 16 (5-6), 841-845.
90. Goodacre, R. Making sense of the metabolome using evolutionary computation: seeing the wood with the trees. J. Exp. Bot. 2005, 56 (410), 245-254.
91. Kopka, J.; Schauer, N.; Krueger, S.; Birkemeyer, C.; Usadel, B.; Bergmuller, E.; Dormann, P.; Weckwerth, W.; Gibon, Y.; Stitt, M.; Willmitzer, L.; Fernie, A. R.; Steinhauser, D. GMD@CSB.DB: the Golm Metabolome Database. Bioinformatics 2005, 21 (8), 1635-1638.
92. Jenkins, H.; Hardy, N.; Beckmann, M.; Draper, J.; Smith, A. R.; Taylor, J.; Fiehn, O.; Goodacre, R.; Bino, R. J.; Hall, R.; Kopka, J.; Lane, G. A.; Lange, B. M.; Liu, J. R.; Mendes, P.; Nikolau, B. J.; Oliver, S. G.; Paton, N. W.; Rhee, S.; Roessner-Tunali, U.; Saito, K.; Smedsgaard, J.; Sumner, L. W.; Wang, T.; Walsh, S.; Wurtele, E. S.; Kell, D. B. A proposed framework for the description of plant metabolomics experiments and their results. Nat. Biotechnol. 2004, 22 (12), 1601-1606.
93. Jenkins, H.; Johnson, H.; Kular, B.; Wang, T.; Hardy, N. Toward supportive data collection tools for plant metabolomics. Plant Physiol. 2005, 138 (1), 67-77.
94. Wolff, J. C.; Eckers, C.; Sage, A. B.; Giles, K.; Bateman, R. Accurate mass liquid chromatography/mass spectrometry on quadrupole orthogonal acceleration time-of-flight mass analyzers using switching between separate sample and reference sprays. 2. Applications using the dual-electrospray ion source. Anal. Chem. 2001, 73 (11), 2605-2612.
95. Plumb, R. S.; Johnson, K. A.; Rainville, P.; Smith, B. W.; Wilson, I. D.; Castro-Perez, J. M.; Nicholson, J. K. UPLC/MS(E); a new approach for generating molecular fragment information for biomarker structure elucidation. Rapid Commun. Mass Spectrom. 2006, 20 (13), 1989-1994.
96. Schlotterbeck, G.; Ross, A.; Hochstrasser, R.; Senn, H.; Kuhn, T.; Marek, D.; Schett, O. High-resolution capillary tube NMR. A miniaturized 5-microL high-sensitivity TXI probe for mass-limited samples, off-line LC NMR, and HT NMR. Anal. Chem. 2002, 74 (17), 4464-4471.
97. Olson, D. L.; Norcross, J. A.; O'Neil-Johnson, M.; Molitor, P. F.; Detlefsen, D. J.; Wilson, A. G.; Peck, T. L. Microflow NMR: concepts and capabilities. Anal. Chem. 2004, 76 (10), 2966-2974.
98. Hirai, M. Y.; Yano, M.; Goodenowe, D. B.; Kanaya, S.; Kimura, T.; Awazuhara, M.; Arita, M.; Fujiwara, T.; Saito, K. Integration of transcriptomics and metabolomics for understanding of global responses to nutritional stresses in Arabidopsis thaliana. Proc. Natl. Acad. Sci. U.S.A. 2004, 101 (27), 10205-10210.
99. Ippolito, J. E.; Xu, J.; Jain, S.; Moulder, K.; Mennerick, S.; Crowley, J. R.; Townsend, R. R.; Gordon, J. I. An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers. Proc. Natl. Acad. Sci. U.S.A. 2005, 102 (28), 9901-9906.
100. Clish, C. B.; Davidov, E.; Oresic, M.; Plasterer, T. N.; Lavine, G.; Londo, T.; Meys, M.; Snell, P.; Stochaj, W.; Adourian, A.; Zhang, X.; Morel, N.; Neumann, E.; Verheij, E.; Vogels, J. T.; Havekes, L. M.; Afeyan, N.; Regnier, F.; van der Greef, J.; Naylor, S. Integrative biological analysis of the APOE*3-leiden transgenic mouse. Omics 2004, 8 (1), 3-13.
101. Raamsdonk, L. M.; Teusink, B.; Broadhurst, D.; Zhang, N.; Hayes, A.; Walsh, M. C.; Berden, J. A.; Brindle, K. M.; Kell, D. B.; Rowland, J. J.; Westerhoff, H. V.; van Dam, K.; Oliver, S. G. A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat. Biotechnol. 2001, 19 (1), 45-50.
102. Allen, J.; Davey, H. M.; Broadhurst, D.; Heald, J. K.; Rowland, J. J.; Oliver, S. G.; Kell, D. B. High-throughput classification of yeast mutants for functional genomics using metabolic footprinting. Nat. Biotechnol. 2003, 21 (6), 692-696.
103. Jones, G. L.; Sang, E.; Goddard, C.; Mortishire-Smith, R. J.; Sweatman, B. C.; Haselden, J. N.; Davies, K.; Grace, A. A.; Clarke, K.; Griffin, J. L. A functional analysis of mouse models of cardiac disease through metabolic profiling. J. Biol. Chem. 2005, 280 (9), 7530-9.
104. Griffin, J. L.; Cemal, C. K.; Pook, M. A. Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3. Physiol. Genomics 2004, 16 (3), 334-340.
105. Griffin, J. L.; Shockcor, J. P. Metabolic profiles of cancer cells. Nat. Rev. Cancer 2004, 4 (7), 551-561.
106. Plumb, R. S.; Stumpf, C. L.; Gorenstein, M. V.; Castro-Perez, J. M.; Dear, G. J.; Anthony, M.; Sweatman, B. C.; Connor, S. C.; Haselden, J. N. Metabonomics: the use of electrospray mass spectrometry coupled to reversed-phase liquid chromatography shows potential for the screening of rat urine in drug development. Rapid Commun. Mass Spectrom. 2002, 16 (20), 1991-1996.
107. Waters, N. J.; Waterfield, C. J.; Farrant, R. D.; Holmes, E.; Nicholson, J. K. Integrated metabonomic analysis of bromobenzene-induced hepatotoxicity: novel induction of 5-oxoprolinosis. J. Proteome Res. 2006, 5 (6), 1448-1459.
108. Schauer, N.; Zamir, D.; Fernie, A. R. Metabolic profiling of leaves and fruit of wild species tomato: a survey of the Solanum lycopersicum complex. J. Exp. Bot. 2005, 56 (410), 297-307.
109. Moco, S.; Bino, R. J.; Vorst, O.; Verhoeven, H. A.; de Groot, J.; van Beek, T. A.; Vervoort, J.; de Vos, C. H. A liquid chromatography-mass spectrometry-based metabolome database for tomato. Plant Physiol. 2006, 141 (4), 1205-1218.
110. Hamzehzarghani, H.; Kushalappa, A. C.; Dion, Y.; Rioux, S.; Comeau, A.; Yaylayan, V.; Marshall, W. D.; Mather, D. E. Metabolic profiling and factor analysis to discriminate quantitative resistance in wheat cultivars against fusarium head blight. Physiol. Mol. Plant Pathol. 2005, 66 (4), 119-133.
111. Sato, S.; Soga, T.; Nishioka, T.; Tomita, M. Simultaneous determination of the main metabolites in rice leaves using capillary electrophoresis mass spectrometry and capillary electrophoresis diode array detection. Plant J. 2004, 40 (1), 151-163.
112. Jonsson, P.; Johansson, E. S.; Wuolikainen, A.; Lindberg, J.; Schuppe-Koistinen, I.; Kusano, M.; Sjostrom, M.; Trygg, J.; Moritz, T.; Antti, H. Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS data - a potential tool for multi-parametric diagnosis. J. Proteome Res. 2006, 5 (6), 1407-1414.
113. Tagashira, N.; Plader, W.; Filipecki, M.; Yin, Z.; Wisniewska, A.; Gaj, P.; Szwacka, M.; Fiehn, O.; Hoshi, Y.; Kondo, K.; Malepszy, S. The metabolic profiles of transgenic cucumber lines vary with different chromosomal locations of the transgene. Cell. Mol. Biol. Lett. 2005, 10 (4), 697-710.
114. Aharoni, A.; Ric de Vos, C. H.; Verhoeven, H. A.; Maliepaard, C. A.; Kruppa, G.; Bino, R.; Goodenowe, D. B. Nontargeted metabolome analysis by use of Fourier Transform Ion Cyclotron Mass Spectrometry. Omics 2002, 6 (3), 217-234.
115. Garratt, L. C.; Linforth, R.; Taylor, A. J.; Lowe, K. C.; Power, J. B.; Davey, M. R. Metabolite fingerprinting in transgenic lettuce. Plant Biotechnol. J. 2005, 3 (2), 165-174.
116. Sabatine, M. S.; Liu, E.; Morrow, D. A.; Heller, E.; McCarroll, R.; Wiegand, R.; Berriz, G. F.; Roth, F. P.; Gerszten, R. E. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation 2005, 112 (25), 3868-3875.
117. Brindle, J. T.; Antti, H.; Holmes, E.; Tranter, G.; Nicholson, J. K.; Bethell, H. W.; Clarke, S.; Schofield, P. M.; McKilligin, E.; Mosedale, D. E.; Grainger, D. J. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat. Med. 2002, 8 (12), 1439-1444.
118. Griffin, J. L.; Sang, E.; Evens, T.; Davies, K.; Clarke, K. Metabolic profiles of dystrophin and utrophin expression in mouse models of Duchenne muscular dystrophy. FEBS Lett 2002, 530 (1-3), 109-116.
119. Kawashima, H.; Oguchi, M.; Ioi, H.; Amaha, M.; Yamanaka, G.; Kashiwagi, Y.; Takekuma, K.; Yamazaki, Y.; Hoshika, A.; Watanabe, Y. Primary biomarkers in cerebral spinal fluid obtained from patients with influenza-associated encephalopathy analyzed by metabolomics. Int J. Neurosci. 2006, 116 (8), 927-936.
120. Yang, J.; Xu, G.; Zheng, Y.; Kong, H.; Pang, T.; Lv, S.; Yang, Q. Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases. J. Chromatogr., B: Analyt. Technol. Biomed. Life Sci. 2004, 813 (1-2), 59-65.