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1、代谢组学研究技术及应用代谢组学研究技术及应用生物系生物系 赵闯营赵闯营代谢组学主要研究技术代谢组学主要研究技术目目 录录什么是代谢组学什么是代谢组学?代谢组学应用举例代谢组学应用举例 Gene一一 mRNA Protein Metabolite系系统统生生物物学学一、什么是代谢组学一、什么是代谢组学 1.代谢组学的提出 Jeremy K.Nicholson教授作为代谢组学的先行者，被誉为国际“代谢组学之父”.Metabonomics:thequantitativemeasurementofthemulti-parametricmetabolicresponseoflivingsystemsto
2、pathophysiologicalstimuliorgeneticmodifications.生物系统对生理和病理刺激以及基因改变的代谢应答的定量测定.2.代谢组学的概念 在现有的英文表述中，代谢组学同时存在两个不同的词汇和概念，即metabonomics和metabolomics.Metabolomics存在多个定义，但其精髓是：对一个生物系统的细胞在给定时间和给定条件下所有小分子代谢物质的定量分析(thequantitativemeasurementofalllowmolecularweightmetabolitesinanorganismcellsataspecifiedtimeund
3、erspecificenvironmentalconditions).Metabolomics 着重研究的是单个细 胞或细胞类型中所有的小分子成分和波动规律,或许可以叫做细胞代谢组学.多用于植物和微生物系统.Metabonomics代谢组学是关于定量描述生物内源性代谢物质的整体及其对内因和外因变化应答规律的科学.(Metabonomicsisthebranchofscienceconcernedwiththequantitativeunderstandingsofthemetabolitecomplementofintegratedlivingsystemsanditsdynamicrespo
4、nsestothechangesofbothendogenousfactors(suchasphysiologyanddevelopment)andexogenousfactors(suchasenvironmentalfactorsandxenobiotics).因此，Metabolomics可以译作代谢物组学.Metabolomics是Metabonomics的一个组成部分.3.3.代谢组学的发展代谢组学的发展198219831984198919992000200120022007Van De GreefVan De Greef:publication of MS for urine pr
5、ofilingSadler,Buckingham and Sadler,Buckingham and Nicholson:Nicholson:First publication on 1H-NMR of blood and plasmaNicholson,et al.:Nicholson,et al.:Multi-componentanalysisofspectradatafromraturineNicholson and Wilson:NMR spectroscopy of biofluidsNicholson:Nicholson:Definition of MetabonomicsHase
6、lden,et al.:Haselden,et al.:First independent Pharma publication of MetabonomicsNicholson,Lindon,and Nicholson,Lindon,and Holmes:Holmes:Publication in Nature on MetabonomicsHolmes and Antti Holmes and Antti Explanation of statistics in MetabonomicsIncreasing#of publicationsIncreasing#of publications
7、二、代谢组学主要研究技术二、代谢组学主要研究技术代谢组学分析流程代谢组学分析流程样品的采集及预处理样品的采集及预处理数据的采集数据的采集数据的分析及解释数据的分析及解释代谢组学各分析流程技术代谢组学各分析流程技术AbstractProton-NMR-basedmetabonomicsoffersarareopportunityasadefinitivescreeningtechniqueforbiofluidsandtissuebiopsies.Theprocedureisextraordinaryinthatitallowsthecompletebiochemicalpicturetobee
8、xaminedatonetimeandisabletodetectsubtlebutrepeatedlyconsistentdisparitiesthatmaybeoccurringindifferent,andperhapsunrelated,biochemicalpathways.Suchmetabolicresponsestoaninitialperturbationinhomeostasismaybefollowedoverasequentialtime-coursetotheireventualdissipationorconsequentsequelae.Theapplicatio
9、nofthistechniqueisbeginningslowlytofilterintotheareaofendocrineresearchandhasbeenusedtoexaminelong-termanddiffusephysiologicalalterationsthatmayoccurfollowingsucheventsasanabolicsteroidtreatmentofcattleandtheexposureofendometrialcellstotamoxifen.Althoughonlymodestinroadshavebeenmadesofar,thistechniq
10、uepromisesimmensepotentialforfutureresearcheswithintheendocrinefield.Contents1.Introduction2.Protonnuclearmagneticresonancespectroscopy3.Themetabonomicapproachandpatternrecognition4.Applicationwithinthebiologicalfield5.Hormones,drugsandtheendocrinesystemReferences1.WhatisMetabonomics?Metabonomics:th
11、equantitativemeasurementofthemulti-parametricmetabolicresponseoflivingsystemstopathophysiologicalstimuliorgeneticmodifications.(生物系统对生理和病理刺激以及基因改变的代谢应答的定量测定)2.Principleofproton-NMR在特殊的磁场中，用无线电射频脉冲激发氢原子核，引起氢原子核共振，并吸收能量。在停止射频脉冲后，氢原子核按特定频率发出射电信号，并将吸收的能量释放出来，被体外的接受器收录，经电子计算机处理获得图像3.1H-NMRandmethodsofanalysisNMRdataNLMHCAandPCA.unsupervisedSIMCANNsandPNNssupervised4.Metabonomicapproachinmedicalcare5.Theimmensepotentialofthemetabonomicapproachinthefieldofintermediarymetabolismandendocrinecontrol