Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content

Advertisement

Correlative GC-TOF-MS-based metabolite profiling and LC-MS-based protein profiling reveal time-related systemic regulation of metabolite–protein networks and improve pattern recognition for multiple biomarker selection

  • Published:
Metabolomics Aims and scope Submit manuscript

A novel approach is presented combining quantitative metabolite and protein data and multivariate statistics for the analysis of time-related regulatory effects of plant metabolism at a systems level. For the analysis of metabolites, gas chromatography coupled to a time-of-flight mass analyzer (GC-TOF-MS) was used. Proteins were identified and quantified using a novel procedure based on shotgun sequencing as described recently (Weckwerth et al., 2004b, Proteomics 4, 78–83). For comparison, leaves of Arabidopsis thaliana wild type plants and starchless mutant plants deficient in phosphoglucomutase activity (PGM) were sampled at intervals throughout the day/night cycle. Using principal and independent components analysis, each dataset (metabolites and proteins) displayed discrete characteristics. Compared to the analysis of only metabolites or only proteins, independent components analysis (ICA) of the integrated metabolite/protein dataset resulted in an improved ability to distinguish between WT and PGM plants (first independent component) and, in parallel, to see diurnal variations in both plants (second independent component). Interestingly, levels of photorespiratory intermediates such as glycerate and glycine best characterized phases of diurnal rhythm, and were not influenced by high sugar accumulation in PGM plants. In contrast to WT plants, PGM plants showed an inversely regulated cluster of N-rich amino acid metabolites and carbohydrates, indicating a shift in C/N partitioning. This observation corresponds to altered utilization of urea cycle intermediates in PGM plants suggesting enhanced protein degradation and carbon utilization due to growth inhibition. Among the proteins chloroplastidic GAPDH (At3g26650) was the best discriminator between WT and PGM plants in contrast to the cytosolic isoform (At1g13440) according to the primary effect of mutation located in the chloroplast. The described method is applicable to all kinds of biological systems and enables the unbiased identification of biomarkers embedded in correlative metabolite–protein networks.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AA:

ascorbic acid

Ala:

alanine

Ara/Xyl:

arabinose/xylose

Asn:

asparagine

Asp:

aspartic acid

BA:

benzoic acid

b-Ala:

beta-Alanine

CHO(1–12):

carbohydrate(1–12)

CitA:

citric acid

Citn:

citrulline

CMA:

citramalic acid

Cys:

cysteine

EA:

ethanolamine

F6P:

fructose 6-phosphate

Fru:

fructose

Fuc:

fucose

FumA:

fumaric acid

G1P:

glucose 1-phosphate

G6P:

glucose 6-phosphate

GA:

galactonic acid

GABA:

4-aminobutyric acid

GalOH:

galactinol

Glc:

glucose

Gln:

glutamine

Glu:

glutamic acid

Gly:

glycine

Glyc:

glycerol

GlycA:

glyceric acid

HA:

hydroxylamine

HyPro:

4-hydroxyproline

IAN:

indole-3-acetonitrile

Ile:

isoleucine

iso-SinA:

iso-sinapinic acid

Leu:

leucine

Lys:

lysine

Mal:

maltose

MalA:

malic acid

Man:

mannose

Met:

methionine

myo-IN:

myo-inositol

Orn/Arg:

ornithine/arginine

P:

phosphoric acid

PA:

propylamine-2,3-diol

pGlu:

pyroglutamic acid

Phe:

phenylalanine

Pro:

proline

Psi:

psicose

Put:

putrescine

PyrA:

pyruvic acid

Raf:

raffinose

Rib:

ribose

RibA:

ribonic acid

SalA:

salicylic acid

Ser:

serine

SinA:

sinapinic acid

Spd:

spermidine

Suc:

sucrose

SucA:

succinic acid

TAmam:

tartronic acid 2-(methylaminomethyl)

Thr:

threonine

ThrA:

threonic acid

ThrAL:

threonic acid-1,4-lactone

Tre:

trehalose

Tyr:

tyrosine

UA:

uric acid

Ura:

uracil

Urea:

urea

Val:

valine

ADC:

arginine decarboxylase

AIH:

agmatine iminohydrolase

ARG:

arginase

ASL:

argininosuccinate lyase

ASS:

argininosuccinate synthase

CPA:

N-carbamoylputrescine amidohydrolase

CPS:

carbamoylsynthetase

dSAM:

decarboxylated S-adenosylmethionine

MTA:

5′-methylthioadenosine

OCT:

ornithine carbamoyltransferase

SST:

spermidine synthase; PCA: principal components analysis; ICA: independent components analysis.

References

  • T. Blaschke L. Wiskott (2004) ArticleTitleCuBICA: independent component analysis by simultaneous third- and fourth-order cumulant diagonalization IEEE Trans. Signal Process. 52 1250–1256 Occurrence Handle10.1109/TSP.2004.826173 Occurrence HandleMR2061981

    Article  MathSciNet  Google Scholar 

  • D.C. Boyes A.M. Zayed R. Ascenzi A.J. McCaskill N.E. Hoffman K.R. Davis J. Gorlach (2001) ArticleTitleGrowth stage-based phenotypic analysis of arabidopsis: a model for high throughput functional genomics in plants Plant Cell 13 1499–1510 Occurrence Handle10.1105/tpc.13.7.1499 Occurrence Handle1:CAS:528:DC%2BD3MXlsFKltrk%3D Occurrence Handle11449047

    Article  CAS  PubMed  Google Scholar 

  • Camacho, D., Fuente, A.D.L. and Mendes, P. (2005). The origin of correlations in metabolomics data. Metabolomics (in press).

  • Y. Cao D.D. Williams N.E. Williams (1999) ArticleTitleData transformation and standardization in the multivariate analysis of river water quality Ecol. Appl. 9 669–677

    Google Scholar 

  • T. Caspar S.C. Huber C. Somerville (1985) ArticleTitleAlterations in growth, photosynthesis, and respiration in a starchless mutant of Arabidopsis thaliana (L) deficient in chloroplast phosphoglucomutase activity Plant Physiol. 79 11–17 Occurrence Handle1:CAS:528:DyaL2MXlvFehs74%3D

    CAS  Google Scholar 

  • J.O. Castrillo S.G. Oliver (2004) ArticleTitleYeast as a touchstone in post-genomic research: strategies for integrative analysis in functional genomics J. Biochem. Mol. Biol. 37 93–106 Occurrence Handle1:CAS:528:DC%2BD2cXhtlWgt7w%3D Occurrence Handle14761307

    CAS  PubMed  Google Scholar 

  • Cichocki, A. and Amari, S. (2002). Adaptive Blind Signal and Image Processing: Learning Algorithms and Applications. Wiley

  • J.W. Collister G. Rieley B. Stern G. Eglinton B. Fry (1994) ArticleTitleCompound-specific delta-C-13 analyses of leaf lipids from plants with differing carbon-dioxide metabolisms Organic Geochem. 21 619–627 Occurrence Handle10.1016/0146-6380(94)90008-6 Occurrence Handle1:CAS:528:DyaK2cXlslGhtr4%3D

    Article  CAS  Google Scholar 

  • M. Cooper S. Chapman D. Podlich G. Hammer (2002) ArticleTitleThe GP problem: quantifying gene-to-phenotype relationships In Silico Biol. 2 151–164 Occurrence Handle1:CAS:528:DC%2BD38XlsFWitbk%3D Occurrence Handle12066839

    CAS  PubMed  Google Scholar 

  • K. Diamantaras S. Kung (1996) Principal Component Neural Networks Wiley New York

    Google Scholar 

  • O. Fiehn (2002) ArticleTitleMetabolomics – the link between genotypes and phenotypes Plant Mol. Biol. 48 155–171 Occurrence Handle10.1023/A:1013713905833 Occurrence Handle1:CAS:528:DC%2BD38Xht1Kqtr0%3D Occurrence Handle11860207

    Article  CAS  PubMed  Google Scholar 

  • O. Fiehn J. Kopka P. Dormann 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

    Article  CAS  PubMed  Google Scholar 

  • D.R. Geiger J.C. Servaites (1994) ArticleTitleDiurnal regulation of photosynthetic carbon metabolism in C-3 plants Ann. Rev. Plant Physiol. – Plant Mol. Biol. 45 235–256 Occurrence Handle10.1146/annurev.pp.45.060194.001315

    Article  Google Scholar 

  • R. Gerhardt M. Stitt H.W. Heldt (1987) ArticleTitleSubcellular metabolite levels in spinach leaves – regulation of sucrose synthesis during diurnal alterations in photosynthetic partitioning Plant Physiol. 83 399–407 Occurrence Handle1:CAS:528:DyaL2sXhsleisL0%3D

    CAS  Google Scholar 

  • Y. Gibon O. Blaesing J. Hannemann P. Carillo M. Hohne J. Hendriks N. Palacios J. Cross J. Selbig M. Stitt (2004a) ArticleTitleA Robot-based platform to measure multiple enzyme activities in Arabidopsis using a set of cycling assays: comparison of changes of enzyme activities and transcript levels during diurnal cycles and in prolonged darkness Plant Cell 16 3304–3325 Occurrence Handle10.1105/tpc.104.025973 Occurrence Handle1:CAS:528:DC%2BD2MXhtVKlsQ%3D%3D

    Article  CAS  Google Scholar 

  • Y. Gibon O.E. Blasing N. Palacios-Rojas D. Pankovic J.H.M. Hendriks J. Fisahn M. Hohne M. Gunther M. Stitt (2004b) ArticleTitleAdjustment of diurnal starch turnover to short days: depletion of sugar during the night leads to a temporary inhibition of carbohydrate utilization, accumulation of sugars and post-translational activation of ADP-glucose pyrophosphorylase in the following light period Plant J. 39 847–862 Occurrence Handle10.1111/j.1365-313X.2004.02173.x Occurrence Handle1:CAS:528:DC%2BD2cXpt1GntLo%3D

    Article  CAS  Google Scholar 

  • M. Glinski T. Romeis C. Witte S. Wienkoop W. Weckwerth (2003) ArticleTitleStable isotope labeling of phosphopeptides for multiparallel kinase target analysis and identification of phosphorylation sites Rapid Commun. Mass Spectrom. 17 1579–1584 Occurrence Handle10.1002/rcm.1093 Occurrence Handle1:CAS:528:DC%2BD3sXlsFGmurY%3D Occurrence Handle12845583

    Article  CAS  PubMed  Google Scholar 

  • R. Goodacre (2003) ArticleTitleExplanatory analysis of spectroscopic data using machine learning of simple, interpretable rules Vibrat. Spectroscopy 32 33–45 Occurrence Handle10.1016/S0924-2031(03)00045-6 Occurrence Handle1:CAS:528:DC%2BD3sXls1alsb4%3D

    Article  CAS  Google Scholar 

  • R. Goodacre S. Vaidyanathan W.B. Dunn G.G. Harrigan D.B. Kell (2004) ArticleTitleMetabolomics by numbers: acquiring and understanding global metabolite data Trends Biotechnol. 22 245–252 Occurrence Handle10.1016/j.tibtech.2004.03.007 Occurrence Handle1:CAS:528:DC%2BD2cXjtl2lt7k%3D Occurrence Handle15109811

    Article  CAS  PubMed  Google Scholar 

  • J.M. Halket A. Przyborowska S.E. Stein W.G. Mallard S. Down R.A. Chalmers (1999) ArticleTitleDeconvolution gas chromatography mass spectrometry of urinary organic acids – potential for pattern recognition and automated identification of metabolic disorders Rapid Commun. Mass Spectrom. 13 279–284 Occurrence Handle10.1002/(SICI)1097-0231(19990228)13:4<279::AID-RCM478>3.0.CO;2-I Occurrence Handle1:CAS:528:DyaK1MXhtlKntrw%3D Occurrence Handle10097403

    Article  CAS  PubMed  Google Scholar 

  • Hyvärinen, A., Karhunen, J. and Oja, E. (2001). Independent Component Analysis. J. Wiley

  • J. Ihmels R. Levy N. Barkai (2004) ArticleTitlePrinciples of transcriptional control in the metabolic network of Saccharomyces cerevisiae Nat. Biotechnol. 22 86–92 Occurrence Handle10.1038/nbt918 Occurrence Handle1:CAS:528:DC%2BD2cXls1ar Occurrence Handle14647306

    Article  CAS  PubMed  Google Scholar 

  • D.B. Kell (2002) ArticleTitleMetabolomics and machine learning: explanatory analysis of complex metabolome data using genetic programming to produce simple, robust rules Mol. Biol. Rep. 29 237–241 Occurrence Handle10.1023/A:1020342216314 Occurrence Handle1:CAS:528:DC%2BD38Xnt1agur8%3D Occurrence Handle12241064

    Article  CAS  PubMed  Google Scholar 

  • D. Kell P. Mendes (2000) Snapshots of systems: metabolic control analysis and biotechnology in the postgenomic era A.J. Cornish-Bowden M.L. Cardenas (Eds) Technological and Medical Implications of Metabolic Control Analysis Kluwer Academic Publishers Netherland 2–25

    Google Scholar 

  • E. Kovats (1958) ArticleTitleGas-Chromatographische Charakterisierung Organischer Verbindungen. 1. Retentionsindices Aliphatischer Halogenide, Alkohole, Aldehyde Und Ketone Helv. Chim. Acta 41 1915–1932 Occurrence Handle10.1002/hlca.19580410703

    Article  Google Scholar 

  • C. Leonard R. Sacks (1999) ArticleTitleTunable-column selectivity and time-of-flight detection for high-speed GC/MS Anal. Chem. 71 5177–5184 Occurrence Handle10.1021/ac990631f Occurrence Handle1:CAS:528:DyaK1MXmsVensLk%3D

    Article  CAS  Google Scholar 

  • J. Lippincott I. Apostol (1999) ArticleTitleCarbamylation of cysteine: a potential artifact in peptide mapping of hemoglobins in the presence of urea Anal. Biochem. 267 57–64 Occurrence Handle10.1006/abio.1998.2970 Occurrence Handle1:CAS:528:DyaK1MXotlGqtw%3D%3D Occurrence Handle9918655

    Article  CAS  PubMed  Google Scholar 

  • J.K. Nicholson J. Connelly J.C. Lindon E. Holmes (2002) ArticleTitleMetabonomics: a platform for studying drug toxicity and gene function Nat. Rev. Drug Discovery 1 153–161 Occurrence Handle10.1038/nrd728 Occurrence Handle1:CAS:528:DC%2BD38Xhs1aksbw%3D

    Article  CAS  Google Scholar 

  • J.K. Nicholson J.C. Lindon E. Holmes (1999) ArticleTitle‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data Xenobiotica 29 1181–1189 Occurrence Handle10.1080/004982599238047 Occurrence Handle1:CAS:528:DyaK1MXns12ms7k%3D Occurrence Handle10598751

    Article  CAS  PubMed  Google Scholar 

  • K.H. Ott N. Aranibar B.J. Singh G.W. Stockton (2003) ArticleTitleMetabonomics classifies pathways affected by bioactive compounds. Artificial neural network classification of NMR spectra of plant extracts Phytochemistry 62 971–985 Occurrence Handle10.1016/S0031-9422(02)00717-3 Occurrence Handle1:CAS:528:DC%2BD3sXhtVeltrY%3D Occurrence Handle12590124

    Article  CAS  PubMed  Google Scholar 

  • J. Peng J.E. Elias C.C. Thoreen L.J. Licklider S.P. Gygi (2003) ArticleTitleEvaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome J. Proteome Res. 2 43–50 Occurrence Handle10.1021/pr025556v Occurrence Handle1:CAS:528:DC%2BD38XnvVOitro%3D Occurrence Handle12643542

    Article  CAS  PubMed  Google Scholar 

  • U. Roessner C. Wagner J. Kopka R.N. Trethewey L. Willmitzer (2000) ArticleTitleSimultaneous analysis of metabolites in potato tuber by gas chromatography–mass spectrometry Plant J. 23 131–142 Occurrence Handle10.1046/j.1365-313x.2000.00774.x Occurrence Handle1:CAS:528:DC%2BD3cXlvFWnsrc%3D Occurrence Handle10929108

    Article  CAS  PubMed  Google Scholar 

  • U. Roessner-Tunali E. Urbanczyk-Wochniak T. Czechowski A. Kolbe L. Willmitzer A.R. Fernie (2003) ArticleTitleDe novo amino acid biosynthesis in potato tubers is regulated by sucrose levels Plant Physiol. 133 683–692 Occurrence Handle10.1104/pp.103.024802 Occurrence Handle1:CAS:528:DC%2BD3sXosVaqtLo%3D Occurrence Handle14512520

    Article  CAS  PubMed  Google Scholar 

  • Roweis, S.T. and Saul, L.K. (2000). Nonlinear dimensionality reduction by locally linear embedding. Science 290, 2323–2326

    Google Scholar 

  • H. Sauter M. Lauer H. Fritsch (1991) ArticleTitleMetabolic profiling of plants – a new diagnostic-technique Acs Symp. Series 443 288–299 Occurrence Handle1:CAS:528:DyaK3MXhsFyqu7Y%3D

    CAS  Google Scholar 

  • M. Scholz S. Gatzek A. Sterling O. Fiehn J. Selbig (2004) ArticleTitleMetabolite fingerprinting: detecting biological features by independent component analysis Bioinformatics 20 2447–2454 Occurrence Handle10.1093/bioinformatics/bth270 Occurrence Handle1:CAS:528:DC%2BD2cXos1GisLs%3D Occurrence Handle15087312

    Article  CAS  PubMed  Google Scholar 

  • Scholz, M. and Vigário, R. (2002). Nonlinear PCA: a new hierarchical approach. Proc. ESANN. 439–444

  • R. Steuer J. Kurths O. Fiehn W. Weckwerth (2003) ArticleTitleObserving and interpreting correlations in metabolomic networks Bioinformatics 19 1019–1026 Occurrence Handle10.1093/bioinformatics/btg120 Occurrence Handle1:CAS:528:DC%2BD3sXktVCgs7g%3D Occurrence Handle12761066

    Article  CAS  PubMed  Google Scholar 

  • L.W. Sumner P. Mendes R.A. Dixon (2003) ArticleTitlePlant metabolomics: large-scale phytochemistry in the functional genomics era Phytochemistry 62 817–836 Occurrence Handle10.1016/S0031-9422(02)00708-2 Occurrence Handle1:CAS:528:DC%2BD3sXhtVeltr0%3D Occurrence Handle12590110

    Article  CAS  PubMed  Google Scholar 

  • D.L. Tabb W.H. McDonald J.R. Yates (2002) ArticleTitleDTASelect and contrast: tools for assembling and comparing protein identifications from shotgun proteomics J. Proteome Res. 1 21–26 Occurrence Handle10.1021/pr015504q Occurrence Handle1:CAS:528:DC%2BD38XhsFektro%3D Occurrence Handle12643522

    Article  CAS  PubMed  Google Scholar 

  • B.H. ter Kuile H.V. Westerhoff (2001) ArticleTitleTranscriptome meets metabolome: hierarchical and metabolic regulation of the glycolytic pathway FEBS Lett. 500 169–171 Occurrence Handle10.1016/S0014-5793(01)02613-8 Occurrence Handle1:CAS:528:DC%2BD3MXkvVelsL4%3D Occurrence Handle11445079

    Article  CAS  PubMed  Google Scholar 

  • O. Thimm O. Blasing Y. Gibon A. Nagel S. Meyer P. Kruger J. Selbig L.A. Muller S.Y. Rhee M. Stitt (2004) ArticleTitleMAPMAN: a user-driven tool to display genomics data sets onto diagrams of metabolic pathways and other biological processes Plant J. 37 914–939 Occurrence Handle10.1111/j.1365-313X.2004.02016.x Occurrence Handle1:CAS:528:DC%2BD2cXjtFChu78%3D Occurrence Handle14996223

    Article  CAS  PubMed  Google Scholar 

  • R.N. Trethewey A.J. Krotzky L. Willmitzer (1999) ArticleTitleMetabolic profiling: a Rosetta Stone for genomics? Curr. Opin. Plant Biol. 2 83–85 Occurrence Handle10.1016/S1369-5266(99)80017-X Occurrence Handle1:STN:280:DyaK1M3lslCqug%3D%3D Occurrence Handle10322197

    Article  CAS  PubMed  Google Scholar 

  • E. Urbanczyk-Wochniak A. Luedemann J. Kopka J. Selbig U. Roessner-Tunali L. Willmitzer A.R. Fernie (2003) ArticleTitleParallel analysis of transcript and metabolic profiles: a new approach in systems biology EMBO Rep. 4 989–993 Occurrence Handle10.1038/sj.embor.embor944 Occurrence Handle1:CAS:528:DC%2BD3sXnslaqt7g%3D Occurrence Handle12973302

    Article  CAS  PubMed  Google Scholar 

  • T. Veriotti R. Sacks (2001) ArticleTitleHigh-speed GC and GC/time-of-flight MS of lemon and lime oil samples Anal. Chem. 73 4395–4402 Occurrence Handle10.1021/ac010239d Occurrence Handle1:CAS:528:DC%2BD3MXlslyqt7o%3D Occurrence Handle11575784

    Article  CAS  PubMed  Google Scholar 

  • M.R. Viant (2003) ArticleTitleImproved methods for the acquisition and interpretation of NMR metabolomic data Biochem. Biophys. Res. Commun. 310 943–948 Occurrence Handle10.1016/j.bbrc.2003.09.092 Occurrence Handle1:CAS:528:DC%2BD3sXnvVylurY%3D Occurrence Handle14550295

    Article  CAS  PubMed  Google Scholar 

  • A. Wagner (1997) ArticleTitleCausality in complex systems Biol. Philos. 14 83–101 Occurrence Handle10.1023/A:1006580900476

    Article  Google Scholar 

  • J.T. Watson G.A. Schultz R.E. Tecklenburg J. Allison (1990) ArticleTitleRenaissance of Gas-chromatography time-of-flight mass-spectrometry – meeting the challenge of capillary columns with a beam deflection instrument and time array detection J. Chromatogr. 518 283–295 Occurrence Handle10.1016/S0021-9673(01)93190-5 Occurrence Handle1:CAS:528:DyaK3cXmt1ertL0%3D Occurrence Handle2254386

    Article  CAS  PubMed  Google Scholar 

  • Webb, J.W., Gates, S.C., Comiskey, J.P. and Weber, D.F. (1986). Metabolic profiling of corn plants using HPLC and GC/MS. Abstracts of Papers of the American Chemical Society 191, 70-ANYL

  • W. Weckwerth (2003) ArticleTitleMetabolomics in systems biology Ann. Rev. Plant Biol. 54 669–689 Occurrence Handle10.1146/annurev.arplant.54.031902.135014 Occurrence Handle1:CAS:528:DC%2BD3sXntFSns78%3D

    Article  CAS  Google Scholar 

  • W. Weckwerth O. Fiehn (2002) ArticleTitleCan we discover novel pathways using metabolomic analysis? Curr. Opin. Biotechnol. 13 156–160 Occurrence Handle10.1016/S0958-1669(02)00299-9 Occurrence Handle1:CAS:528:DC%2BD38Xis1CltL0%3D Occurrence Handle11950569

    Article  CAS  PubMed  Google Scholar 

  • W. Weckwerth M.E. Loureiro K. Wenzel O. Fiehn (2004a) ArticleTitleDifferential metabolic 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

    Article  CAS  Google Scholar 

  • Weckwerth, W., Tolstikov, V. and Fiehn, O. (2001). Metabolomic characterization of transgenic potato plants using GC/TOF and LC-MS analysis reveals silent metabolic phenotypes. Proceedings of the 49th ASMS Conference on Mass spectrometry and Allied Topics, American Society of Mass Spectrometry, Chicago, pp. 1–2

  • W. Weckwerth K. Wenzel O. Fiehn (2004b) 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

    Article  CAS  Google Scholar 

  • S. Wienkoop M. Glinski N. Tanaka V. Tolstikov O. Fiehn W. Weckwerth (2004a) ArticleTitleLinking protein fractionation with multidimensional monolithic RP peptide chromatography/mass spectrometry enhances protein identification from complex mixtures even in the presence of abundant proteins Rapid Commun. Mass Spectrom. 18 643–650 Occurrence Handle10.1002/rcm.1376 Occurrence Handle1:CAS:528:DC%2BD2cXivVCgsLc%3D

    Article  CAS  Google Scholar 

  • S. Wienkoop D. Zoeller B. Ebert U. Simon-Rosin J. Fisahn M. Glinski W. Weckwerth (2004b) ArticleTitleCell-specific protein profiling in Arabidopsis thaliana trichomes: identification of trichome-located proteins involved in sulfur metabolism and detoxification Phytochemistry 65 1641–1649 Occurrence Handle10.1016/j.phytochem.2004.03.026 Occurrence Handle1:CAS:528:DC%2BD2cXmtVCjs7o%3D

    Article  CAS  Google Scholar 

  • H. Winter S.C. Huber (2000) ArticleTitleRegulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes Crit. Rev. Biochem. Mol. Biol. 35 253–289 Occurrence Handle1:CAS:528:DC%2BD3cXntFajtrk%3D Occurrence Handle11005202

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wolfram Weckwerth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morgenthal, K., Wienkoop, S., Scholz, M. et al. Correlative GC-TOF-MS-based metabolite profiling and LC-MS-based protein profiling reveal time-related systemic regulation of metabolite–protein networks and improve pattern recognition for multiple biomarker selection. Metabolomics 1, 109–121 (2005). https://doi.org/10.1007/s11306-005-4430-9

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11306-005-4430-9

Key words: