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82ChinJNatMedMar.2008Vol16No1220083623,,,,,300193,,,,;;;;;R28A167223651(2008)0220082207doi:10.3724/SP.J.1009.2008.000822008203202(No.30630075)(No.2007BAI41B00)3:,,,E2mail:li2uchangxiao@vip.163.com,6(Bristol2Meyers2Squibb,Elililly,Hoffmann2LaRoche,NovoNordisk,Pfizer,Pharmacia),,,NMR,[1],,(FDA),,[226]TheSamuelRobertsBasilNikolauEveWurtele,JohnInnesCentreStevenoliver,WageningenLeiden,MaxPlanckInstituteOliverFiehnLeibniz,ChibaKeioPara2digmGenetics,Syngenta,PioneerHybrid,Exelixis,LargeScaleBiology,Unilever,INSILICO,Nu2mico,Metanomics,INVIVO,,Phe2nomenomeDiscoveries,Unigen(NIH),,,,,,2007122008362ChinJNatMedMar.2008Vol16No1283,,,[7215]NMR2,,,2-200572006SpringerLinkMetabolomics,Nature,JournalofPro2teomeResearch,,[16219]3.13.1.1;,,:,3.1.2GC,LC,CE2MSNMR:3.23.2.1,(),,(orthogonalsignalcorrection,OSC),OSC(),,,OSC,,,,,OSC3.2.2(unsupervised),(),,,,():(principalcomponentsanalysis,PCA)(nonlinearmapping,NLM)(hierarchicalclustera2nalysis,HCA)3.2.3(supervised),,,,()()(validationset)(testset)PCA(partialleastsquares,PLS)(neuralnetwork,NN),SIMCA(softindependentmodelingofclassanalogy)(PLS2discriminantanalysis,PLS2DA),(ANN)84ChinJNatMedMar.2008Vol16No1220083623.2.4,,,,,NMR,Pfizer6200113(COMET),,,,[1]3:/3.2.5(ConnectionsMapDB),KEGG,EcoCyc,EcoCycandmetacyc,BRENDA,LIGAND,MetaCyc,UMBBD,WIT2,EMP,IRIS,AraCyc,PathDB,(ExPASy),(mainmetabolicpathwaysonInternet,MMP),Duke,Arizona,IRIS,AraCyc,,,,,,,,,,,,,,,HPLC(AchDANE52TH),,(),DA[20],-[21]IVCI21018,,[22],,,,;(),,,,,,,(),(),,2008362ChinJNatMedMar.2008Vol16No1285,Aardema,[23]Nicholson,,-,[24],,,,,,[25][26]COMET:,HNMR[27,28]COMET:NMR,,2(),(),(),();DMP777();,;NMR:,(),,[29,30],NMR,,,[31],(highresolutionMagicAngleSpinning,lAS)NMR,22,CoA;Garrod[31,32]HRMASHNMR(,),,(silent2gene),,Kleno[33],Coen[34],,,Grifin[35]KyotoWist2ar,()2,;()HNMRCoAI,,;,86ChinJNatMedMar.2008Vol16No122008362;,;;,,,,;,,,,(1),(2),(3)[36],,,,,,,,,,,,,,,4:7.1,4:,,,,7.2,,,,,,,,,,,,,7.3,,,,,,,7.412000,206000,40020%,70%,,,,2008362ChinJNatMedMar.2008Vol16No1287,,,,,[1]LindonJC,NicholsonJK,HolmesE,etal.Contemporaryissuesintoxicologytheroleofmetabonomicsintoxicologyanditseval2uationbytheCOMETproject[J].ToxicolApplPharmacol,2003,187(3):13721461[2]OliverSG.Yeastasanavigationalaidingenomeanalysis[J].Metabology,1997,143(5):1483214841[3]EspinaJR,ShockcorJP,HerronWJ.Detectionofinvivobiomar2kersofphospholipiodosisusingNMR2basedmetabonomicap2proachers[J].MagnResonChem,2001,39:55925651[4]ShockcorJP,HolmesE.Metabonomicapplicationsintoxicityscreeninganddiseasediagnosis[J].CurrTopMedChem,2002,2(1):352511[5](LiuCX).[J].(ChinTraditHerbDrugs),2004,35(6):60126051[6]LiuCX,LiC,LinDH,etal.Significanceofmetabonomicsindrugdiscoveryanddevelopment[J].AsianJDrugMetabPhar2macokinet,2004,4(2):872961[7](LiuCX),(WangYY),(ZhangBL),..:1:[C]1:,2007:2231[8](LiuCX)..:.:[C].:,2007:42281[9](XuGW)..:1:[C].:,2007:292311[10](WangGJ)..:1:[C].:,2007:312341[11](LiFM),(LuXM),(XiongZL).-.:1:[C].:,2007:342361[12](GaoXM)..:1:[C].:,2007:362381[13](JiaW),(LiuCX)..:1:[C].:,2007:392411[14](TangHR)..:1:[C].:,2007:412431[15](ChengYY)..:1:[C].:,2007:441[16]WuXJ,LinYP,SongLN,etal.Applicationofprincipalcompo2nentanalysisfordataprocessinmetabonomicsstudies[J].Asi2anJDrugMetabPharmacokinet,2005,5(4):28722941[17](WuXJ),(LiuCX),(YuanYJ).[J].(ActaPharmSin),2006,41(1):472531[18](XuM),(LinDH),(LiuCX).[J].(ActaPharmSin),2005,40(9):76927741[19](WuXJ),(YuanYJ),(LiuCX).[J].(JChemIndEng),2005,56(1):1819218251[20](HuangYR),(WeiGL),(XiaoSH),.[J].(ChinTraditHerbDrugs),2005,36(3):30123051[21]WatkinsSM,ReifsnyderPR,PanHJ.Lipidmetabolome2wideeffectsofthePPARgammaagonistrosiglitazone[J].LipidRes,2002,43(11):1809218171[22]SlimRM,RobertsonDG,AlbassamM,etal.Effectofdexam2ethasoneonthemetabonomicsprofileassociatedwithphosphod2iesteraseinhibitor2inducedvascularlesionsinrats[J].ToxicolApplPharmacol,2002,183(2):10821091[23]AardemaMJ,MacGregorJT.Toxicologyandgenetictoxicologyintheneweraoftoxicogenomics:impactof2omicstech2nologies[J].MutatRes,2002,499(1):132251[24]QiuJ.Acultureinthebalance:traditionalChinesemedicineandwesternsciencefacealmostirreconcilabledifferencescansystemsbiologybringthemtogether?[J].Nature,2007,448:12621281[25]QiuJ.BacktothefutureforChineseherbalmedicines[J].NatRevDrugDiscov,2007,6(7):50625071[26]LindonJC,NicholsonJK,HolmesE,etal.Contemporaryissuesintoxicologytheroleofmetabonomicsintoxicologyanditseval2uationbytheCOMETproject[J].ToxicolApplPharmacol,2003,187(3):13721461[27]NicholsonJK,LindonJC,HolmesE.Metabonomics:under2standingthemetabolicresponsesoflivingsystemstopathophysi2ologicalstimuliviamultivariatestatisticalanalysisofbiologicalNMRspectroscopicdata[J].Xenobiotica,1999,29(11):88ChinJNatMedMar.2008Vol16No1220083621181211891[28]NicholsonJK,ConnellyJ,LindonJC,etal.Metabonomics:aplatformforstudyingdrugtoxicityandgenefunction[J].NatRevDrugDiscov,2002,1(2):15321611[29]RobertaonDG,ReilyMD,SiglerRE,etal.Metabonomics:evaluationofnuclearmagneticresonance(NMR)andpatternrecognitiontechnologyforrapidinvivoscreeningofliverandkidneytoxicants[J].ToxicolSci,2000,57(2):32623371[30]HolmesE,NichollsAW,LindonJC,e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