肝臟蛋白質組計劃的實施與毒理學發展的機遇演示文稿目前一頁\總數一百一十三頁\編于十五點（優選）肝臟蛋白質組計劃的實施與毒理學發展的機遇目前二頁\總數一百一十三頁\編于十五點曼哈頓原子彈研制計劃人類基因組計劃阿波羅登月計劃人類歷史上的三大科技工程羅斯福批準,耗資20億美元原子半徑10-10m原子體積10-30m3人體半徑100m人體體積100m3太陽系半徑1012m太陽系體積1034m3克林頓、布萊爾批準，耗資30億美元肯尼迪批準,耗資240億美元目前三頁\總數一百一十三頁\編于十五點人類基因組計劃開創了

“基因組時代”目前四頁\總數一百一十三頁\編于十五點基因組學向蛋白質組學“求助”!

Nature409:747,15Feb.2001

Andnowforproteome

“現在輪到蛋白質組”Science291:1221,16Feb.2001ProteomicsinGenomeland“基因組大地中的蛋白質組學”目前五頁\總數一百一十三頁\編于十五點PROTEIN目前六頁\總數一百一十三頁\編于十五點轉錄組一種細胞、組織或生物體所對應的全套mRNARNA基因組生物體所擁有的全套染色體上的全部基因DNA蛋白質組一種細胞、組織或生物體所對應的全套蛋白質PROTEIN功能執行體遺傳信息載體目前七頁\總數一百一十三頁\編于十五點

基因和蛋白質并不存在嚴格的線性關系

ORF并不預示一定存在相對應的功能性基因

mRNA水平并非與蛋白質的表達水平對應翻譯后修飾及同工蛋白質(Isoforms)等現象在基因水平無從表現蛋白質與蛋白質的相互作用難以在基因水平得以認識基因組與轉錄組不能取代蛋白質組目前八頁\總數一百一十三頁\編于十五點翻譯后修飾相互作用構象變化翻譯后拼接移位胞質胞核蛋白質調節的多樣性生命的“萬花筒”目前九頁\總數一百一十三頁\編于十五點蛋白質功能的群體性目前十頁\總數一百一十三頁\編于十五點繩墻扇茅蛇樹蛋白質作用的整體性目前十一頁\總數一百一十三頁\編于十五點探索生命奧秘的直接對象蛋白質組

生命體的統一性源于基因組生命體的多樣性、復雜性、功能性、表型源于蛋白質組1463-4x1043x109103(1012)

目前十二頁\總數一百一十三頁\編于十五點

Pteomicsismoreofaconceptthanadefinedtechnology,anditreferstoanyprotein-basedapproachthathasthecapacitytoprovidenewinformationaboutproteins

onagenomewidescale.“Proteomicsincludesnotonlytheidentificationand

quantificationofproteinsbutalsothedeterminationof

their:

localization

modifications

interactions

activities

function目前十三頁\總數一百一十三頁\編于十五點報告提要蛋白質組學產生的時代背景“國際人類肝臟蛋白質組計劃”的目標與意義蛋白質組學與毒理學/環境醫學目前十四頁\總數一百一十三頁\編于十五點DNA序列圖≠基因圖人類基因組中1/3以上基因未曾確認基因確認的基本層次--蛋白質水平天書解讀天書Science291:1221,2001目前十五頁\總數一百一十三頁\編于十五點全面揭示重大疾病發生發展機制的基礎蛋白質組單基因病—遺傳病多基因病—腫瘤等

重大疾病發生發展機制單一基因單一蛋白基因群蛋白質群轉錄組蛋白質組????目前十六頁\總數一百一十三頁\編于十五點發現大量新型藥靶與新藥的源泉蛋白質組最重要的疾病100-150每種疾病相關的基因10每個基因相關的蛋白質3–10藥靶蛋白總數

3000-15,000

現有藥物約2000種85％是針對目前已知的500種藥靶6-30倍藥靶有待發現目前十七頁\總數一百一十三頁\編于十五點啟動人類蛋白質組計劃勢在必行！探索人體生命奧秘的直接對象全面揭示重大疾病發生發展機制的基礎發現大量新型藥靶與新藥的源泉

人類基因組序列及基因注釋人類蛋白質組VIP:VeryImportantProteome目前十八頁\總數一百一十三頁\編于十五點人類蛋白質組計劃的

主要科學目標驗證人類基因組計劃推測的基因，注釋基因組闡明蛋白質組的調控模式并與轉錄組進行對比建立蛋白質群/組裝體，蛋白質復合物或蛋白質機器,即連鎖圖建立人體生理學、病理學的蛋白質組基礎目前十九頁\總數一百一十三頁\編于十五點1463-4x1043x109103(1012)

基因組計劃蛋白質組計劃目前二十頁\總數一百一十三頁\編于十五點目前二十一頁\總數一百一十三頁\編于十五點Bodyfluidmostaccessibleforbiomarkerdiscoveryinanimalandhumans.LiverKidneyOrganBodyFluidBrainImmuneOrgans/VesselsIntestineOtherTissuesCSFFecesEndocrine/ParacrineSecretionsBileUrineAir/BALFLymphLungsEyesSkinOralCavitySweatSalivaTearsVenousBloodArterialBloodSerum10%90%SerumProteinsNon-InformativeAbundantProteinsi.e.albumin,IgG,etc.InformativeLowAbundanceProteinsEnrichmentStrategiesforInformativeSerumProteins:SELDI

SerumImmunosubtraction

目前二十二頁\總數一百一十三頁\編于十五點人類肝臟蛋白質組計劃里程碑蛋白表達譜蛋白連鎖圖亞細胞定位圖修飾譜人類基因組計劃

里程碑遺傳圖物理圖序列圖目前二十三頁\總數一百一十三頁\編于十五點InitiativesofHumanProteomeProject(HPP)HPPPHumanPlasmaProteomeProject,USAHLPPHumanLiverProteomeProject,ChinaPSIProteomicsStandardsInitiativeUKHBPP

HumanBrainProteomeProject,GermanyHAIHumanAntibodyInitiativeSweden目前二十四頁\總數一百一十三頁\編于十五點Whyisliver?wwwww.HLPP.HUPO為何研究肝臟?目前二十五頁\總數一百一十三頁\編于十五點肝臟功能的多樣性與重要性能量——能量轉換、儲存物質——代謝（活性分子的合成、毒性分子的分解）信息——信息分子的合成與分泌目前二十六頁\總數一百一十三頁\編于十五點肝臟為其它組織提供能量—可氧化底物組織的活力依賴于高能鍵的連續生成。肝臟產生大部分脂肪酸，后者是禁食狀態下能量的基本來源。肝臟是給食狀態下由過剩糖合成脂肪酸的主要部位。目前二十七頁\總數一百一十三頁\編于十五點藥物毒物營養物生物異源物生物轉化目前二十八頁\總數一百一十三頁\編于十五點化學多樣性向體內的生物轉化體系提出嚴峻挑戰1.2×107種以上的化學物(CAService’slist)以每周約8000種的速率增加常用化學物在63,000種以上大約11,500種，作為食物或藥物制劑添加物攝入其余的50,000種，為潛在的環境污染物目前二十九頁\總數一百一十三頁\編于十五點人類發育過程中造血組織的興替造血系統的發育必需肝臟的“培育”目前三十頁\總數一百一十三頁\編于十五點合成大多數循環血漿蛋白合成和分泌血漿蛋白是肝臟實質細胞——肝細胞的獨有功能（肝細胞占肝臟總細胞數的60%及肝臟質量的約80%）最有特征的血漿蛋白是白蛋白，在大多數哺乳動物中占總血漿蛋白的55-60%凝血酶、抗凝因子、溶栓酶等目前三十一頁\總數一百一十三頁\編于十五點肝臟再生機體再生能力最強的器官終生保持旺盛的再生能力目前三十二頁\總數一百一十三頁\編于十五點肝臟中包含的“組”(-ome)Metabolicgenomics→Metabolome

(代謝組)Energygenomics→Energome

(能量組)Pharmacogenomics→Pharmacome

(藥理組)Toxicogenomics→Toxicome

(毒理組)Regeneratinggenomics

→Regenerome

(再生組)目前三十三頁\總數一百一十三頁\編于十五點全球及中國肝炎的流行病學統計

全球:3.5億攜帶者中國:1.8億攜帶者死亡:23萬人/年疾病負擔:500億元人民幣治療手段:抗病毒,保肝降 酶,抗纖維化,免疫治療等缺點:病毒易反彈,病 情易反復目前三十四頁\總數一百一十三頁\編于十五點肝炎向肝癌的惡性轉化

難以遏制全世界現有3.5億慢性乙肝病毒（HBV）攜帶者，占世界人口的5%，亞洲和非洲HBV攜帶率為8-15%

HBV攜帶者中50-70%病毒復制活躍，為慢性乙肝

慢性乙肝病人肝硬化發生率為2-20%，代償性肝硬化發展成失代償性肝硬化為20-23%，發展成肝癌的占6-15%中國的慢性乙肝病人中，約25-40%最終將死于肝硬化或合并肝癌HBV攜帶者最終死于相關肝病的危險性，男性為50%，女性為15%

目前三十五頁\總數一百一十三頁\編于十五點全球:100萬人/年中國:50萬人/年死亡:約45萬人/年疾病負擔:400億元人民幣治療手段:手術切除(只有 15%-20%)治療效果:術后易轉移,易復 發,五年存活率 40-50%全球及中國肝癌的流行病學統計目前三十六頁\總數一百一十三頁\編于十五點原發性肝癌的治療水平亟待突破世界上每年有100萬新發原發性肝癌病人，其中40-50%在我國

我國原發性肝癌發病率和死亡率均位居第二位

近20年來我國肝癌的發病率上升近40%原發性肝癌一般起病較隱匿，早期缺乏典型臨床表現，初診大多已屬中晚期

初診肝癌病人中，只有15-20%的病人具備手術條件這些病人術后5年生存率僅為40-50%

肝癌是致死率最高的惡性腫瘤之一目前三十七頁\總數一百一十三頁\編于十五點重大肝病的發生發展無法歸咎于少數幾個基因或蛋白質所呈現的功能狀態和信號通路從蛋白質組層面上“全景式”揭示肝臟疾病的生理病理機制是解決重大肝病的根本出路肝炎病毒肝臟/肝細胞肝炎肝硬化/纖維化原發肝癌肝癌轉移多因素、多步驟的發病機制目前三十八頁\總數一百一十三頁\編于十五點肝臟是人類蛋白質組計劃的首批目標！目前三十九頁\總數一百一十三頁\編于十五點Prometheusstolefirefromthegodsandgaveittomortals.PrometheusBoundHeraclesLiberatePrometheusHLPP—ModernPrometheusMythPrometheus

LiverEagleLiverdiseases

HeraclesHLPP目前四十頁\總數一百一十三頁\編于十五點人類肝臟蛋白質組計劃

HumanLiverProteomeProject(HLPP)國際HLPP共同體目前四十一頁\總數一百一十三頁\編于十五點Generateanintegrativeapproachleadingtoacomprehensivefunctionalmapoftheliver

Expandliverproteometoits“PHYSIOME”and“PATHOME”todramaticallyacceleratethedevelopmentofdiagnostics,preventionandtherapeuticstowardsitsdiseases

Developstandardoperatingprocedures(SOPs)forotherHUPOInitiativesVISION目前四十二頁\總數一百一十三頁\編于十五點HUPOWorkshop,Bethesda,April28-29,2002

BroadinterestsandsupportsforinitiatingHLPP

HUPOLiverProteomeWorkshop,Beijing,October22-24,2002

GettingconsensusviewforscientificobjectivesofHLPP

HUPO1stWorldCongress,Versailles,November21-24,2002

Co-chairsofHLPP:Drs.FuchuHe,JohnBergeronandChristianBréchot

HLPPPlanningCommittee:17members;May2003ProposalsaboutWorkingPlanofHLPP

Dr.JohnBergeron:Jan31,2003(Management);

Dr.FuchuHe:Feb17,2003(ScientificStrategy)Dr.FuchuHe:Mar22,2003(ActionPlan);

Dr.ChristianBrechot:Mar31,2003(Sampling)

HLPPOffice,March18,2003HUPOLPPWorkshop,Bethesda,July17-18,2003

NIHparticipatingHUPO2ndWorldCongress,Montreal,Oct.8-12,2003

Dr.FuchuHewasappointedastheexecutiveChairofHLPP(2003-2005)HUPOHLPPSatelliteMeeting,Montreal,Oct.12,2003SetupExecutiveCommittee&9Sub-committees,ActionPlanatPilotPhaseFrenchliversampleswerecollectedanddistributedamong8labs,May,2004HUPOHLPPSatelliteMeeting,Beijing,Oct.24,2004ChinesepartofHLPPwasofficiallylaunched,Nov.,2004Chineseliversampleswerecollectedanddistributedamong7labs,Feb.,2005MISION目前四十三頁\總數一百一十三頁\編于十五點表達譜修飾譜定位圖連鎖圖樣品庫抗體庫數據庫HLPP的科學目標---肝臟蛋白質組的“太陽系”3-D圖ORF組目前四十四頁\總數一百一十三頁\編于十五點肝臟蛋白質組與

肝臟生理、病理的銜接肝臟蛋白質組代謝組毒理組藥理組再生組肝炎組肝癌組能量組目前四十五頁\總數一百一十三頁\編于十五點作為分泌器官，肝臟合成大多數的循環血漿蛋白

肝臟轉錄組“肝臟蛋白質組計劃”和“血漿蛋白質組計劃”的整合肝臟蛋白質組血漿蛋白質組?目前四十六頁\總數一百一十三頁\編于十五點基因組肝臟蛋白質組肝臟轉錄組基因組、轉錄組和蛋白質組的集成證實推測基因對比調控模式

目前四十七頁\總數一百一十三頁\編于十五點重要功能蛋白質肝病藥物靶標肝病診斷標志物人類肝臟蛋白質組目前四十八頁\總數一百一十三頁\編于十五點肝炎病毒肝臟/肝細胞感染肝炎肝硬化/纖維化原發肝癌肝癌轉移重大肝病預警、診斷、預防、治療的關鍵環節“東亞病夫”“肝病大國”1億多肝炎病毒攜帶者1000億多/年醫療費用目前四十九頁\總數一百一十三頁\編于十五點SOPsSpecimenBankingPlatformsWorkingteamGlobalCollaborationExpressionProfileORFeomeAntibodiesBioinformatics…

ModificationProfileSubcellularLocalizationProtein-ProteinInteractionAntibodiesBioinformaticsIntegrateproteomewithtranscriptomeCompareproteomeswithinhealthanddiseasedliverTimeLinesPilotPhase(2003-2005)PhaseII(2006-2010)目前五十頁\總數一百一十三頁\編于十五點OutlineBackgroundProgressoftheHLPP-ProgressreportonexpressionprofilingInitiationoftheCNHLPPNextwork目前五十一頁\總數一百一十三頁\編于十五點Progress-ExpressionprofilingEvaluationoftechnologiesBioinformaticsset-upSamplingandpreparationPreviewwithhumanfetalliverPrimaryanalysisofFrenchlivertissues目前五十二頁\總數一百一十三頁\編于十五點ProgressEvaluationoftechnologiesBioinformaticsset-upSamplingandPreparationPreviewwithhumanfetalliverPrimaryanalysisofFrenchlivertissues目前五十三頁\總數一百一十三頁\編于十五點Majorconclusionsfromthevaluationoftechnologies–16standardproteins/7labsHighmolecularweightandlowabundanceproteinsarelessdetectableby2DE.Proteinswithonlythreeorderofmagnitudecouldbeidentifiedin2DE,butproteinswithfourorderofmagnitudecouldbeidentifiedinshotguntechnology.Morepeptides(redundant)wereidentifiedforhighMWproteinsinshotguntechnology.Somesimilarproteinswereidentified(notproteingroup),suggestingthecriteriafordistinguishingsimilarproteinsshouldbemorestrict.目前五十四頁\總數一百一十三頁\編于十五點ProgressEvaluationoftechnologiesBioinformaticsset-upSamplingandPreparationPreviewwithhumanfetalliverPrimaryanalysisofFrenchlivertissues目前五十五頁\總數一百一十三頁\編于十五點HLPPExperimentalDatabaseMWSDataClient…GUI，WebServices,APIFilesInterchange,DMBSDumpDatasynchronizeDatasubmissionExperimentreports,data,files…

HLPPDataMirrorMWSDataClientMWSDataClientMWSDataClientMWSDataClientMWSServerAdministratorHLPPDataMirrorSubmissionPackagesRepositoryHLPPProjectManagementDatabaseHLPPProjectManagementSystemHLPPParticipatingLaboratoriesHLPPDataCenterTheHLPPDataManagementSystem

ArchitectureBasedonMyWorkSpaceSystem(MWS)目前五十六頁\總數一百一十三頁\編于十五點CurrentStandarddraftofHLPPSampleInformationProteinextractionConcentrationMeasurementSeparationGel-based2DEGel1D-IEFGel1D-SDSLC-basedRPLCSCXLCSAXLCSECTrapDesaltingDigestionIonsourceMALDIAutoflexUltraflexABI4700ESIQstarQTofMicroLCQLTQMassspectrometryTOFTOFTOFUltraflexABI4700QTOFQstarQTofMicroITMSLCQLTQPeaklistgenerationABI4700QStarAutoflexTurboSequestMasslynxFlexAnalysisPeaklistpreprocessingGPSpeaklistpreprocessProtein/peptideidentificationMascotSequestProteinlistgenerationAutoflexGPSBiotoolsQstarBuildSummaryDTASelectBioworksAutoQuest目前五十七頁\總數一百一十三頁\編于十五點Proteinidentificationisbasedontheanalysisofpeptidesgeneratedbyproteolyicdigestion.Whenthedetectedpeptidesmatchmanyproteinsandcannotidentifyauniqueprotein,theresultwillbepresentedintheformofagroupofpossibleproteins.

DefinitionofProteinGROUP

目前五十八頁\總數一百一十三頁\編于十五點CriteriaforproteinidentificationIontrapXCorr(highest)≥1.9(1),2.2(2),3.75(3);DeltaCn≥0.1;RSp≤4.ABI-TOF/TOFProteinscore≥59(Rank1forthespot)Q-TOForQ-STARProteinscore>thresholdPeptidescore>“thescoreforidentity”or29MALDI-TOFProteinscore>thresholdTheproteinsinfirstreport(multi-proteinforthemixture)目前五十九頁\總數一百一十三頁\編于十五點ProgressEvaluationoftechnologiesBioinformaticsset-upSamplingandpreparationPreviewwithhumanfetalliverPrimaryanalysisofFrenchlivertissues目前六十頁\總數一百一十三頁\編于十五點EvaluationoftheSOPsforthesubcellularfractionationObject:FindtheoptimummethodofpretreatmentSample:LivertissuesofC57miceSubcellular:Mitochondria,Golgi,PM,Nucleus,ER,CytoplasmSamplepretreatmentFreshtissuesFrozenhomogenisedtissuesFrozentissues目前六十一頁\總數一百一十三頁\編于十五點Purity(Westernblotting):Freshtissues>frozenhomogenizedtissues>frozentissuesTheyieldofproteins:Freshtissues>frozenhomogenizedtissues>frozentissuesIntegrity(TEM):Freshtissues>frozenhomogenizedtissuesSummary目前六十二頁\總數一百一十三頁\編于十五點ProgressEvaluationoftechnologiesBioinformaticsset-upSamplingandPreparationPreviewwithhumanfetalliverPrimaryanalysisofFrenchlivertissues目前六十三頁\總數一百一十三頁\編于十五點ItisagiantambitiousobjectiveandgivesagreatchallengetoembryonicproteomicsItisnecessarytocarryoutapreviewbeforetheformallaunchingofthisprojectScience302:1316,Nov.21,2003Nature425:441,Oct.2,2003目前六十四頁\總數一百一十三頁\編于十五點AverageThroughputofthePlatform2DESystem

12Gel/3DaysAuto-SpotDigestSystem

1152spots/DayMSandMS/MSSystem

500-1000Spots/Day目前六十五頁\總數一百一十三頁\編于十五點TheflowchartofCCPITfortheproteinexpressionprofileofhumanfetalliver目前六十六頁\總數一百一十三頁\編于十五點Theareascalesbeforeandafterisoformprocessingingroupandproteinlevelsrespectively.Inproteinlevel,theredcircularityareasrepresentthenumberofconfirmedproteinsandtheyellowannulusareasrepresentthenumberofpossibleproteins.Non-isogroups19%Extensivelyconfirmed81%Groups41%Confirmed59%Non-isoforms43%Isoforms57%contribute

545

additionalproteins

and

eliminate763

groupscontribute

545

additionalproteins

and

eliminate1335

possible

proteinsIn

Protein

LevelIn

Group

Levelconfirmed:1950possible:

2593extensivelyconfirmed:2495non-isoformpossible:

1258目前六十七頁\總數一百一十三頁\編于十五點ACBChromosomaldistributionofHFLproteome-encodinggenes目前六十八頁\總數一百一十三頁\編于十五點FunctionalModulesinplasmamembrane目前六十九頁\總數一百一十三頁\編于十五點ProgressEvaluationoftechnologiesBioinformaticsset-upSamplingandPreparationPreviewwithhumanfetalliverPrimaryanalysisofFrenchlivertissues目前七十頁\總數一百一十三頁\編于十五點

ReferenceLabsforHLPPExpressionProfilingProject

FuchuHe&XiaohongQian(BeijingInstituteofRadiationMedicine)RongZeng(ShanghaiInstituteforBiologicalSciences)PengyuanYang(FudanUniversity)SiqiLiu(BeijingGenomicsInstitute,ChineseAcademyofSciences)目前七十一頁\總數一百一十三頁\編于十五點LauraBeretta(FHCRC,USA)RichardJ.Simpson(RoyalMelbourneHospital,Australia)

AngelikaGorg(TechnischeUniversitatMunchen,Germany)MarkBaker/JunhongSun(APAF,Australia)目前七十二頁\總數一百一十三頁\編于十五點OutlineBackgroundProgressoftheHLPPInitiationoftheCNHLPPNextwork目前七十三頁\總數一百一十三頁\編于十五點CNHLPPOverviewThefirstphase:2004-2005Fundingfromcentralgovernment:10millionUSdollars ChineseMOST:jointlyfundedbyNationalProgramon KeyBasicResearchProjects(973),NationalHigh-tech R&DProgram(863),andNationalKeyTechnologiesR&D Programmeininthefirstphase.LocalandInstitutionalfunding:3.5millionUSdollars8subprojects70institutes,universities,andcompaniesinvolvedLong-termsupportasanationalproject(2006~2020)目前七十四頁\總數一百一十三頁\編于十五點CelebrationofCNHLPPOfficialLaunching(BeijingInstituteofRadiationMedicine)目前七十五頁\總數一百一十三頁\編于十五點KeylabsBeijingInstituteofRadiationMedicine目前七十六頁\總數一百一十三頁\編于十五點Consultingcommittee(5)ORFeome&PPISubproject,ZeguangHanChairFuchuHeHeadquartersBPRCModificationProfilesubproject,YunCaiExpressionProfileSubproject,XiaohongQianStructuralBiologySubproject,WeiminGongBioinformaticssubproject,YixueLiNewTechnologysubproject,YukuiZhangAntibodysubproject,Qi-HongSunLocalizationMappingSubproject,XueminZhang目前七十七頁\總數一百一十三頁\編于十五點Morethan10workshopshavebeenheld目前七十八頁\總數一百一十三頁\編于十五點Briefprogressofsomesubprojects

ProteinmodificationProteinlocalizationProteinstructureNewproteomicstechnologies目前七十九頁\總數一百一十三頁\編于十五點AnalysisofproteinphosphorylationbycombinationofIMAC,PhosphatasewithBiologicalMassSpectrometrym/zPeptidemixtureProteinsCandidatephosphopeptidesIdentificationofphosphorylatedsitesDIGESTIMACMALDI-TOFMSAnalysisPhosphatasedigestMS/MSAnalysisandDatabaseSearchingm/zPhosphopeptideConfirmationm/zMetastableionsofphosphopeptides目前八十頁\總數一百一十三頁\編于十五點O60716

GSLApSLDpSLRKP15924GLPSPYNMSpSAPGpSRO75379NLLEDDpSDEEEDFFLRRApSpSKGGGGYTC*QSGSGWDEFTKO95210HSpSWGDVGVGGSLKP16157RDpSRDVDEEKELLDFVPKP02671ADpSGEGDFLAEGGGVRP35221TPEELDDpSDFETEDFDVRP02730

YQpSSPAKPDSSFYKQ13813WRpSLQQLAEERYQSSPAKPDSSFpYKQ15019IYHLPDAEpSDEDEDFKEQTRYQSSPAKPDSpSFYKQ16828SNIpSPNFNFMGQLLDFERRYQSSPAKPDpSSFYKQ99959RLEISPDpSpSPERAHYTHSDYQYSQRP04792GPpSWDPFRLPEEWSQWLGGSSWPGYVRPLPPAAIEpSPAVAAPAYSRQ9H3Z4SLpSTSGESLYHVLGLDKTr:O95810SLEETLHTVDLpSpSDDDLPHDEEALEDpSAEEKVEESRP05386KEEpSEEpSDDDM*GFGLFDKEEpSEEpSDDDMGFGLFDTr:Q8NEN5pSQpSLPTTLLSPVRP08559YHGHpSMSDPGVSYRTr:Q9HAP4ESEALPEKEGEELGEGERPEEDAAALELpSpSDEAVEVEEVIEESRP11277TpSPVSLWSRLpSpSSWESLQPEPSHPYTr:Q9NQA7WLDEpSDAEMELRIdentifiedphosphopeptidesequencesfromHFL目前八十一頁\總數一百一十三頁\編于十五點Proteinisolationandpurificationbylectin(Glycosylation)目前八十二頁\總數一百一十三頁\編于十五點Co-localizationandlocomotionoftheGFPfusionproteinandDsRedDsRed-MemGreenmergeGFPGFP-fusedPrTNF-treatedGFP-fusedmutantTNF-treatedGFP-fusedPr目前八十三頁\總數一百一十三頁\編于十五點StructuralproteomicsCloned900genesfromliverExpressedproductsofmorethan100genesDeterminedthestructuresof3proteinsbyX-rayDeterminedthestructuresof2proteinsbyNMR目前八十四頁\總數一百一十三頁\編于十五點Diphosphoglyceratemutase(DPGM)X-rayProgrammedcelldeath5(PDCD5)NMR目前八十五頁\總數一百一十三頁\編于十五點Beijing(National)ProteomeResearchCenterChineseProteomeDevelopmentCenter目前八十六頁\總數一百一十三頁\編于十五點TheAntibodyBankofHumanLiverProteomeProjectEstablishment,characterization,andapplicationofantibodiesagainsthumanliverproteins

Qi-HongSunBeijingInstituteofRadiationMedicine(BIRM)BeijingProteomeResearchCenter(BPRC)目前八十七頁\總數一百一十三頁\編于十五點AntigensMyelomacellsHybridomacellsmAbsDiagnosticsTherapeuticsProteomicsResearch

ProfilingIdentificationQuantificationLocalizationModificationInteractionFunctionLargeantibodycollectionforproteomics目前八十八頁\總數一百一十三頁\編于十五點AntibodyDatabaseAntibodyBankSamples5000liverproteinsHLPPAntibodyBankAntibodychips目前八十九頁\總數一百一十三頁\編于十五點10%ofHLPPAntibodyBankStandardsanddatabaseofHUPOHLPP/HAIMicroarrayandotherantibody-basedtechnology90%10%HLPPAntibodyBankatPilotPhase目前九十頁\總數一百一十三頁\編于十五點Antigenpreparation

Fractionatedliverproteins-Unknown/native/multi-antigensRecombinantproteinsSynthesizedpeptidesAntibodygenerationHybridomacelllines–mAbs(murine/rabbit)Polyclonalantibodies–IgG(Rabbit)/orIgY(chicken)AntibodycharacterizationandapplicationClassandsubclass,ELISA,IH,WB,andIPAntibodymicroarrayandotherantibody-basedtechnologyGeneralApproach目前九十一頁\總數一百一十三頁\編于十五點AdultFetalDiseasedIHcharacterizationofmAbsagainsthumanliverproteins目前九十二頁\總數一百一十三頁\編于十五點ProgresssummaryofHLPPAntibodyBankingProject

AntigenpreparationforimmunizationFractionatedliverproteins–nucleus,membrane,microsome,mitochondrial,cytosolic,andplasmaproteinsPurifiedrecombinantproteinantigens–215Synthesizedpeptidesfromliver-specificproteins–44AntibodypreparationandcharacterizationEstablishedhybridomacelllines–1085CharacterizedmAbs–862formorethan100differentproteinsRabbitpAbs–50AntibodyApplication

Depletionofhigh-abundantproteinsImmunohistochemistryIsolationofproteincomplexes目前九十三頁\總數一百一十三頁\編于十五點LabsofHLPPAntibodyBankingProjectNational(China):Qi-HongSun/JianenGao,MingLi,MinZhao,DalingZhu,ChaonengJi,GangCheng,ZhinanChen,BoquanJing,JianWang/LinWu,XiaoningWang/YingLin,ZhengLi,JinliangYang,andJieTang.Internationalcollaboration:

HUPO-HAI(Dr.Uhlen)FHCRC/NCI-IBDC(Dr.Lee)GermanSystemsBiologyProject(Drs.Meyer,Ueffing)目前九十四頁\總數一百一十三頁\編于十五點Workingplan

Antibodydatasheet–ElectronicsubmissionformAntibodylist–Website/HLPPAntibodydatabaseAntibodydemands/applicationsAntibodyqualitycontrolAntibodyexchange,collection,anddistributionScaleofantibodybankAntibody-basedtechnologyInternationalcollaboration目前九十五頁\總數一百一十三頁\編于十五點目前九十六頁\總數一百一十三頁\編于十五點OutlineBackgroundProgressoftheHLPPInitiationoftheCNHLPPNextwork目前九十七頁\總數一百一十三頁\編于十五點ResearchprojectsDistributetheChinesespecimenstoreferencelabsoutsideChinaEstablishtheSOPsfortheblackracialpeople`sliversampleComprehensivelyanalyzethedataoftheproteinsexpressingprofileoftheFrenchspecimensEstablishtheSOPsfortheprotein-proteininteractionsandORFeomeInitiatevirtuallydiseasedliverproteomesubprojectInitiatevirtuallyproteomicmodificationandlocalizationsubprojects目前九十八頁\總數一百一十三頁\編于十五點CoordinationContinuetodiscussthecooperationwithotherinitiatives(e.g.MRPP,HPPP,PSI,HAI,etc.)orotherprogramme(e.g.SystemsBiologyProjectofGermany)EstablishtheheadquartersoftheHLPPContinuetopropagandizetheHLPPtothepublicandpriva