Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) was applied for the analysis of complex metabolite profiles from mouse spleen. The resulting two-dimensional chromatograms proved that mass spectral quality and sensitivity were largely improved by the enhanced resolution and zone compression, which are features of GC × GC operation, when compared to classical one-dimensional GC-TOF methods. The improved peak capacity of GC × GC allowed for peaks to be detected that could previously not be separated in one-dimensional GC. A measure of the combined power of chromatographic and mass spectral deconvolution resolution is called “analytical purity”, with higher values indicating less pure peaks. GC × GC-TOF lead to the detection of 1200 compounds with purity better than 0.2, compared to 500 compounds with purity up to 2.5 in one-dimensional GC-TOF. The compounds identified include many of the compounds previously reported in NMR studies and other methods on mammalian tissues. Spleen samples of several obese NZO mice and lean C57BL/6 control strains were analyzed in order to demonstrate the applicability of GC × GC-TOF for biomarker identification.
Similar content being viewed by others
References
H.O. Adami D. Trichopoulos (2003) ArticleTitleObesity and mortality from cancer N. Engl. J. Med 348 1623–1624 Occurrence Handle10.1056/NEJMp030029 Occurrence Handle12711736
J. Allen H.M. Davey D. Broadhurst (2003) ArticleTitleHigh throughput classification of yeast mutants for functional genomics using metabolic footprinting Nat. Biotechnol. 21 692–696 Occurrence Handle10.1038/nbt823 Occurrence Handle1:CAS:528:DC%2BD3sXktFSlu78%3D Occurrence Handle12740584
J. Beens R. Tijssen J. Blomberg (1998) ArticleTitleComprehensive two-dimensional gas chromatography (GC × GC) as a diagnostic tool J. High Resolut. Chromatogr 21 63–64 Occurrence Handle10.1002/(SICI)1521-4168(19980101)21:1<63::AID-JHRC63>3.0.CO;2-P Occurrence Handle1:CAS:528:DyaK1cXhslyrtr4%3D
L.C. Cantley (2002) ArticleTitleThe phosphoinositide 3-kinase pathway Science 296 1655–1657 Occurrence Handle1:CAS:528:DC%2BD38XktlChu7s%3D Occurrence Handle12040186
J. Dallüge L.L.P. Stee Particlevan X. Xu et al. (2002) ArticleTitleUnraveling the composition of very complex samples by comprehensive gas chromatography coupled to time-of-flight mass spectrometry, Cigarette smoke J. Chromatogr. A 974 169–184 Occurrence Handle10.1016/S0021-9673(02)01384-5 Occurrence Handle12458936
J. Dallüge R.J.J. Vreuls J. Beens U.A.T. Brinkman (2002) ArticleTitleOptimization and characterization of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometric detection (GC × GC-TOFMS) J. Sep. Sci 25 201–214 Occurrence Handle10.1002/1615-9314(20020301)25:4<201::AID-JSSC201>3.0.CO;2-B
M.M. Deursen Particlevan J. Beens H.-G. Janssen P.A. Leclercq C.A. Cramers (2000) ArticleTitleEvaluation of time of flight mass spectrometric detection for fast gas chromatography J. Chromatogr. A 878 205–213 Occurrence Handle10.1016/S0021-9673(00)00300-9 Occurrence Handle10866067
O. Fiehn (2002) ArticleTitleMetabolomics – the link between genotype and phenotype Plant Mol. Biol. 48 155–171
O. Fiehn (2003) ArticleTitleMetabolic networks of Cucurbita maxima phloem Phytochemistry 62 875–886 Occurrence Handle10.1016/S0031-9422(02)00715-X Occurrence Handle1:CAS:528:DC%2BD3sXhtVelsbY%3D Occurrence Handle12590115
O. Fiehn J. Kopka P. Dörmann T. Altmann R.N. Trethewey L. Willmitzer (2000) ArticleTitleMetabolite profiling for plant functional genomics Nat. Biotechnol. 18 1157–1161 Occurrence Handle10.1038/81137 Occurrence Handle1:CAS:528:DC%2BD3cXotVSmtL0%3D Occurrence Handle11062433
O. Fiehn J. Kopka R.N. Trethewey L. Willmitzer (2000) ArticleTitleIdentification of uncommon plant metabolites based on calculation of elemental compositions using gas chromatography and quadrupole mass spectrometry Anal. Chem. 72 3573–3580 Occurrence Handle10.1021/ac991142i Occurrence Handle1:CAS:528:DC%2BD3cXksFOru74%3D Occurrence Handle10952545
M.Y. Hirai M. Yano D.B. Goodenowe (2004) ArticleTitleIntegration of transcriptomics and metabolomics for understanding of global responses to nutritional stresses in Arabidopsis thaliana Proc. Natl. Acad. Sci. USA 101 10205–10210 Occurrence Handle10.1073/pnas.0403218101 Occurrence Handle1:CAS:528:DC%2BD2cXlvFOhsbw%3D Occurrence Handle15199185
H.C. Keun O. Beckonert J.L. Griffin (2002) ArticleTitleCryogenic probe 13C NMR spectroscopy of urine for metabonomic studies Anal. Chem. 74 4588–4593 Occurrence Handle10.1021/ac025691r Occurrence Handle1:CAS:528:DC%2BD38Xls1Git7c%3D Occurrence Handle12236374
E.M. Kristenson P. Kortyár C. Danielsson M. Kallio M. Brandt J. Makela (2003) ArticleTitleEvaluation of modulators and electron-capture detectors for comprehensive two-dimensional GC of halogenated organic compounds J. Chromatogr. A 1019 65–77 Occurrence Handle10.1016/S0021-9673(03)01237-8 Occurrence Handle1:CAS:528:DC%2BD3sXosVKqsr4%3D Occurrence Handle14650605
O. Lamas J.A. Martínez A. Marti (2004) ArticleTitleEnergy restriction restores the impaired immune response in overweight (cafeteria) rats J. Nutr. Biochem. 15 418–425 Occurrence Handle10.1016/j.jnutbio.2004.02.003 Occurrence Handle1:CAS:528:DC%2BD2cXltF2ktbY%3D Occurrence Handle15219927
E. Ledford C. Billesbach (2000) ArticleTitleJet-cooled thermal modulator for comprehensive multidimensional gas chromatography J. High Resol. Chromatogr. 23 202–204 Occurrence Handle10.1002/(SICI)1521-4168(20000301)23:3<202::AID-JHRC202>3.0.CO;2-5 Occurrence Handle1:CAS:528:DC%2BD3cXkt1Siur8%3D
A.L. Lee K.D. Bartle A.C. Lewis (2001) ArticleTitleA model of peak amplitude enhancement in orthogonal two-dimensional gas chromatography Anal. Chem. 73 1330–1335 Occurrence Handle10.1021/ac001120s Occurrence Handle1:CAS:528:DC%2BD3MXhtVWmtbc%3D
Z. Liu J.B. Phillips (1991) ArticleTitleComprehensive two-dimensional gas chromatography using an on-column thermal modulator interface J. Chromatogr. Sci. 29 227–231 Occurrence Handle1:CAS:528:DyaK3MXlt1Gqu70%3D
P. Marriott R.M. Kinghorn (2000) ArticleTitleNew operational modes for multidimensional and comprehensive gas chromatography by using cryogenic modulation J. Chromatogr. A 866 203–212 Occurrence Handle10.1016/S0021-9673(99)01061-4 Occurrence Handle1:CAS:528:DyaK1MXotVKnt74%3D Occurrence Handle10670810
P. Marriott R. Shellie (2002) ArticleTitlePrinciples and applications of comprehensive two-dimensional gas chromatography Trends Anal. Chem. 21 573–583 Occurrence Handle10.1016/S0165-9936(02)00814-2 Occurrence Handle1:CAS:528:DC%2BD38Xns1akurw%3D
P.J. Marriott (2002) Orthogonal GC–GC L. Mondello A.C. Lewis K.D. Bartle (Eds) Multidimensional Chromatography John Wiley & Sons Chichester, England 77–108
J.K. Nicholson P.J.D. Foxall M. Spraul R.D. Farrant J.C. Lindon (1996) ArticleTitle750 MHz 1H and 1H−13C NMR spectroscopy of human blood plasma Anal. Chem. 67 793–811 Occurrence Handle10.1021/ac00101a004
C. Pendaries H. Tronchère M. Plantavid B. Payrastre (2003) ArticleTitlePhosphoinositide signaling disorders in human diseases FEBS Lett 546 25–31 Occurrence Handle1:CAS:528:DC%2BD3sXkvVKjsro%3D Occurrence Handle12829232
J.B. Phillips J. Beens (1999) ArticleTitleComprehensive two-dimensional gas chromatography: a hyphenated method with strong coupling between two dimensions J. Chromatogr. A 856 331–347 Occurrence Handle10.1016/S0021-9673(99)00815-8 Occurrence Handle1:CAS:528:DyaK1MXmt1entLk%3D Occurrence Handle10526795
J.B. Phillips J. Xu (1995) ArticleTitleComprehensive multi-dimensional gas chromatography J. Chromatogr. A 703 327–334 Occurrence Handle10.1016/0021-9673(95)00297-Z Occurrence Handle1:CAS:528:DyaK2MXmt1OqtLY%3D
A. Schmidt M. Karas T. Dülcks (2003) ArticleTitleEffect of different solution flow rates on analyte ion signals in nano-ESI MS, or: when does ESI turn into nano-ESI J. Am. Soc. Mass Spectrom 14 492–500 Occurrence Handle10.1016/S1044-0305(03)00128-4 Occurrence Handle1:CAS:528:DC%2BD3sXjs1ahtbg%3D Occurrence Handle12745218
Scholz, M., Gatzek, S., Sterling, A., Fiehn, O. and Selbig, J. (in press). Metabolite fingerprinting: detecting biological features by independent component analysis. Bioinformatics.
R. Shellie L. Mondello P. Marriott G. Dugo (2002) ArticleTitleCharacterisation of lavender essential oils by using gas chromatography–mass spectrometry with correlation of linear retention indices and comparison with comprehensive two-dimensional gas chromatography J. Chromatogr. A 970 225–234 Occurrence Handle10.1016/S0021-9673(02)00653-2 Occurrence Handle1:CAS:528:DC%2BD38XnsF2rsrs%3D Occurrence Handle12350096
R.A. Shellie P.J. Marriott C.W. Huie (2003) ArticleTitleComprehensive two dimensional gas chromatography (GC × GC) and GC × GC-quadrupole MS analysis of Asian and American ginseng J. Sep. Sci 26 1185–1192 Occurrence Handle10.1002/jssc.200301404 Occurrence Handle1:CAS:528:DC%2BD3sXntFymtLg%3D
T. Soga Y. Ohashi Y. Ueno H. Naraoka M. Tomita T. Nishioka (2003) ArticleTitleQuantitative metabolome analysis using capillary electrophoresis mass spectrometry J. Proteome Res 2 488–94 Occurrence Handle10.1021/pr034020m Occurrence Handle1:CAS:528:DC%2BD3sXkvFWltrc%3D Occurrence Handle14582645
R. Steuer J. Kurth O. Fiehn W. Weckwerth (2003) ArticleTitleObserving and interpreting correlations in metabolic networks Bio informatics 19 1019–1026 Occurrence Handle1:CAS:528:DC%2BD3sXktVCgs7g%3D
V.V. Tolstikov A. Lommen K. Nakanishi N. Tanaka O. Fiehn (2003) ArticleTitleMonolithic silica-based capillary reversed-phase liquid chromatography/electrospray mass spectrometry for plant metabolomics Anal. Chem 75 6737–6740 Occurrence Handle1:CAS:528:DC%2BD3sXosVSmsLY%3D Occurrence Handle14640754
S. Vaidyanathan J.J. Rowland D.B. Kell R. Goodacre (2001) ArticleTitleDiscrimination of aerobic endospore-forming bacteria via electrospray-ionization mass spectrometry of whole cell suspensions Anal. Chem. 73 4134–4144 Occurrence Handle10.1021/ac0103524 Occurrence Handle1:CAS:528:DC%2BD3MXlsFGmtLo%3D Occurrence Handle11569802
Y. Wang M.E. Bollard H. Keun (2003) ArticleTitleSpectral editing and pattern recognition methods applied to high-resolution magic-angle spinning 1H nuclear magnetic resonance spectroscopy of liver tissues Anal. Biochem. 323 23–26 Occurrence Handle10.1016/j.ab.2003.07.026
W. Weckwerth (2004) ArticleTitleMetabolomics in systems biology Annu. Rev. Plant Biol. 54 669–689 Occurrence Handle10.1146/annurev.arplant.54.031902.135014
W. Weckwerth M.L. Ehlers K. Wenzel O. Fiehn (2004) ArticleTitleMetabolic networks unravel the effects of silent plant phenotypes Proc. Natl. Acad. Sci. USA 101 7809–7814 Occurrence Handle10.1073/pnas.0303415101 Occurrence Handle1:CAS:528:DC%2BD2cXktlOksr0%3D Occurrence Handle15136733
W. Weckwerth K. Wenzel O. Fiehn (2004) ArticleTitleProcess for the integrated extraction, identification and quantification of metabolites, proteins and RNA to reveal their co-regulation in biochemical networks Proteomics 4 78–83 Occurrence Handle10.1002/pmic.200200500 Occurrence Handle1:CAS:528:DC%2BD2cXhtVamur4%3D Occurrence Handle14730673
W. Welthagen J. Schnelle-Kreis R. Zimmermann (2003) ArticleTitleSearch criteria and rules for comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry analysis of airborne particulate matter J. Chromatogr. A 1019 233–249 Occurrence Handle10.1016/j.chroma.2003.08.053 Occurrence Handle1:CAS:528:DC%2BD3sXosVKqs70%3D Occurrence Handle14650618
C. Wittmann J.O. Kromer P. Kiefer T. Binz E. Heinzle (2004) ArticleTitleImpact of the cold shock phenomenon on quantification of intracellular metabolites in bacteria Anal. Biochem. 327 135–139 Occurrence Handle10.1016/j.ab.2004.01.002 Occurrence Handle1:CAS:528:DC%2BD2cXitFKht7g%3D Occurrence Handle15033521
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Welthagen, W., Shellie, R.A., Spranger, J. et al. Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice. Metabolomics 1, 65–73 (2005). https://doi.org/10.1007/s11306-005-1108-2
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11306-005-1108-2