第23期培訓(xùn)課件從基因組學(xué)到精準(zhǔn)醫(yī)學(xué)羽化之路

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于軍BIG- Yes,itishere—theeraof alizedmedicine—whenphysiciansusewhole-genomesequencetoimprovemedicalcare SequencingforBainbridgeetal.2011.SciTransl.Med3:87re3.

于軍BIG- 據(jù) 精準(zhǔn)醫(yī)學(xué)與大 據(jù) 科學(xué)項(xiàng)目：百（十）萬 計(jì) 態(tài)：精準(zhǔn)診斷、治療和健康據(jù) 精準(zhǔn)醫(yī)學(xué)與大 據(jù) 于軍BIG- 精準(zhǔn)醫(yī)學(xué)與大 據(jù)Life

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Falonyetal,Science,2016,Zhernakovaetal,Science,2016, – 于軍BIG- PhysicalScienceLifeS&TForMedicineandWell-beingPENCIL 于軍BIG- KeyGenomics?1975-SouthernDNAhybridizationtechnique?1977-Sanger’schain-terminationandMaxam/Gilbert’schemicalDNAsequencingmethods?1980-Automatedinsituoligonucleotidesynthesisinstrument?1985-Mullis’sdiscoveryofPCRatCetus?1992-Affymatrix(Fodor’sgroup)firstgene-chip?1995-ABI’sfirstautomatedDNAsequencer?2006-2ndgenerationDNAsequenceronmarket?2007andbeyond–singlemoleculesequencingtechniquesandnano-devices 于軍BIG- “吃遍天下”的DNA Messing&Llaca, 于軍BIG- SangerandSangerSequencingFrederickSanger(August13,1918–November19,1958hewasawardedtheNobelPrizeforhisworkinsequencingproteins.HissecondNobelPrize,awardedin1980wasdevelo thetechniquestillusedtoday-'dideoxy'or'Sanger'sequencing.

于軍BIG- ?MariaSklodowska-Curie,1903and1911,fordiscoveryofradioactivity(physics)andlaterforisolatingpureradium(chemistry)?JohnBardeen(1956and1972,forinventionofthetransistor(physics)andforcomingupwiththetheoryofsuperconductivity(physics)?LinusPauling(1954and1962,forresearchintothechemicalbondintermsofcomplexsubstances(chemistry)andforanti-nuclearactivism(peace)?FrederickSanger(1958and1980,fordiscoveringthestructureoftheinsulinmolecule(chemistry)andinventingamethodtodeterminebasesequencesinDNA(chemistry).

于軍BIG- 于軍BIG- DNA SangerCyclicarray√√√√√√√√√√PCR√√√√√√√√√√√√√√√√

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于軍BIG- JimWatson改變了我的想法。認(rèn)識Jim是在我參加?類 容之后，我滿腹狐疑。Watson究竟想如何說服我相信所描述thesophisticatedpurechemisttolookatthismetabolicchartwithinitialskepticism（?位有經(jīng)驗(yàn)的專業(yè)化學(xué)家最初看到這

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于軍BIG- 哺乳動(dòng)物細(xì)胞中RNA是––––––調(diào)控表達(dá)和蛋白質(zhì)翻––RNA修飾組：ModomCarelletalAngewandteChemie,2012,51:RNARNAome＝（Transcriptome；代表?“由于目前各種RNA依賴特殊種類RNA擾檢測（細(xì)胞）所有RNADerks,2015,RNABiology,單細(xì)胞水平RNA直測技術(shù)決定新的人類RNA組 信息流

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sticityTrack-II:The sticityofAffect,Behavior,andCognitionLietalMicrochiicaActa2016,183:941-（unnelingHaqueetalNanoToday.2013,8:56-

Carson&Wanunu,Nanotechnology.2015,26: 于軍BIG- Carson&Wanunu,Carson&Wanunu,

窗口要在1~6nt窗口要在1~6ntRNADNA:4nas4=ATGC;n=長度；max7nasAAmTGCCmJRNA:4 as4=AUGC;max100步長步長：單層石墨烯厚度＝0.35納米（～核苷酸長度均值0.33納米）VenkatesanandBashir,2011,NatureNanotech 于軍BIG-

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5為什么強(qiáng)調(diào)讀長：TheL-WSequencingdepthandcoverage:keyconsiderationsingenomic DavidSims,IanSudbery,NicholasE.Ilott,AndreasHeger&ChrisP.PontingNatureReviewsGenetics15,121–132(2014) 于軍

6KeyParametersforSequencing?Singlemoleculeaccuracy/precision?Allelediscriminationand ficationatsinglemoleculeresolution?Throughputpartition:96-to-384, 103-to-106,and106-?Averageaccuracy:longreadlength>1K,90%;MRL>400,99%;SRL<200,99.9%;?Timing:1–3?Cost:$100per109?Throughput:exomevs.whole