1、Introduction to Bioinformatics1Half day on the web,half month in the lab.saves you- Alan Bleasby201011000AGAGGAAA2000年2月2日，北京大學燕北園300多位教師的家用計算機接入Internet；2001年2月12日，北京大學2000多個本科生宿舍的計算機接入Internet.BioMedXBioinformatics7/13/20223網絡時代的生命科學和生物技術產業討論會9-10 Apr 2001首屆中國生物信息學大會11-13 Apr 20014引自J Postlethwait

2、 & J Hopson著The Nature of Life，1989從基本粒子到生物圈5引自Neil Campbell著Biology第4版，1996生物界病毒細菌6植物細胞動物細胞引自Neil Campbell著Biology第4版，19967引自Neil Campbell著Biology第4版，1996細胞分裂8人類23對染色體9DNA-遺傳密碼的攜帶者10引自Neil Campbell著Biology第4版，199611引自Neil Campbell著Biology第4版,1996胰島素蛋白酶蜘蛛毒素光合作用受體金屬硫蛋白1213Nature 171, 737-734 (1953) (

3、C) Macmillan Publishers Ltd. Molecular structure of Nucleic AcidsWATSON, J. D. & CRICK, F. H. C.Medical Research Council Unit for the Study of Molecular Structure of Biological Systems, Cavendish Laboratory, Cambridge. Figure 1This figure is purely diagrammatic. The two ribbons symbolize the two pho

4、phate-sugar chains, and the horizonal rods the pairs of bases holding the chains together. The vertical line marks the fibre axis.A Structure for Deoxyribose Nucleic AcidWe wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of c

5、onsiderable biological interest.14“Whats Human Genome Project?”“One base One dollar!” - by a taxi driver (and a tax payer)15humanArabidopsis擬南芥Thermotoga maritimaEscherichia coli大腸桿菌Buchnerasp. APSRickettsia prowazekiiUreaplasma urealyticumBacillus subtilisDrosophila melanogasterThermoplasma acidoph

6、ilumPlasmodium falciparumHelicobacter pylori mouseCaenorhabitis elegansratBorrelia burgorferiBorrelia burgorferiAquifex aeolicusNeisseria meningitidis Z2491Mycobacterium tuberculosis 16圖片引自數據引自17Initial sequencing and analysis of the human genome PDFNature 409, 860 - 921 (2001), 15 February 2001 Int

7、ernational Human Genome Sequencing ConsortiumWhitehead Institute for Biomedical Research, Center for Genome Research:ERIC S. LANDER1*, LAUREN M. LINTON1, BRUCE BIRREN1*, CHAD NUSBAUM1*, MICHAEL C. ZODY1*, JENNIFER BALDWIN1, KERI DEVON1, KEN DEWAR1, MICHAEL DOYLE1, WILLIAM FITZHUGH1*, ROEL FUNKE1, DI

8、ANE GAGE1, KATRINA HARRIS1, ANDREW HEAFORD1, JOHN HOWLAND1, LISA KANN1, JESSICA LEHOCZKY1, ROSIE LEVINE1, PAUL MCEWAN1, KEVIN MCKERNAN1, JAMES MELDRIM1, JILL P. MESIROV1, CHER MIRANDA1, WILLIAM MORRIS1, JEROME NAYLOR1, CHRISTINA RAYMOND1, MARK ROSETTI1, RALPH SANTOS1, ANDREW SHERIDAN1, CARRIE SOUGNE

9、Z1, NICOLE STANGE-THOMANN1, NIKOLA STOJANOVIC1, ARAVIND SUBRAMANIAN1 & DUDLEY WYMAN1 The Sanger Centre:JANE ROGERS2, JOHN SULSTON2*, RACHAEL AINSCOUGH2, STEPHAN BECK2, DAVID BENTLEY2, JOHN BURTON2, CHRISTOPHER CLEE2, NIGEL CARTER2, ALAN COULSON2, REBECCA DEADMAN2, PANOS DELOUKAS2, ANDREW DUNHAM2, IA

10、N DUNHAM2, RICHARD DURBIN2*, LISA FRENCH2, DARREN GRAFHAM2, SIMON GREGORY2, TIM HUBBARD2*, SEAN HUMPHRAY2, ADRIENNE HUNT2, MATTHEW JONES2, CHRISTINE LLOYD2, AMANDA MCMURRAY2, LUCY MATTHEWS2, SIMON MERCER2, SARAH MILNE2, JAMES C. MULLIKIN2, ANDREW MUNGALL2, ROBERT PLUMB2, MARK ROSS2, RATNA SHOWNKEEN2

11、 & SARAH SIMS2 Washington University Genome Sequencing CenterROBERT H. WATERSTON3*, RICHARD K. WILSON3, LADEANA W. HILLIER3, JOHN D. MCPHERSON3, MARCO A. MARRA3, ELAINE R. MARDIS3, LUCINDA A. FULTON3, ASIF T. CHINWALLA3, KYMBERLIE H. PEPIN3, WARREN R. GISH3, STEPHANIE L. CHISSOE3, MICHAEL C. WENDL3,

12、 KIM D. DELEHAUNTY3, TRACIE L. MINER3, ANDREW DELEHAUNTY3, JASON B. KRAMER3, LISA L. COOK3, ROBERT S. FULTON3, DOUGLAS L. JOHNSON3, PATRICK J. MINX3 & SANDRA W. CLIFTON3 US DOE Joint Genome Institute:TREVOR HAWKINS4, ELBERT BRANSCOMB4, PAUL PREDKI4, PAUL RICHARDSON4, SARAH WENNING4, TOM SLEZAK4, NOR

13、MAN DOGGETT4, JAN-FANG CHENG4, ANNE OLSEN4, SUSAN LUCAS4, CHRISTOPHER ELKIN4, EDWARD UBERBACHER4 & MARVIN FRAZIER4 Baylor College of Medicine Human Genome Sequencing Center:RICHARD A. GIBBS5*, DONNA M. MUZNY5, STEVEN E. SCHERER5, JOHN B. BOUCK5, ERICA J. SODERGREN5, KIM C. WORLEY5, CATHERINE M. RIVE

14、S5, JAMES H. GORRELL5, MICHAEL L. METZKER5, SUSAN L. NAYLOR6, RAJU S. KUCHERLAPATI7, DAVID L. NELSON & GEORGE M. WEINSTOCK8 RIKEN Genomic Sciences Center:YOSHIYUKI SAKAKI9, ASAO FUJIYAMA9, MASAHIRA HATTORI9, TETSUSHI YADA9, ATSUSHI TOYODA9, TAKEHIKO ITOH9, CHIHARU KAWAGOE9, HIDEMI WATANABE9, YASUSHI

15、 TOTOKI9 & TODD TAYLOR9 Genoscope and CNRS UMR-8030:JEAN WEISSENBACH10, ROLAND HEILIG10, WILLIAM SAURIN10, FRANCOIS ARTIGUENAVE10, PHILIPPE BROTTIER10, THOMAS BRULS10, ERIC PELLETIER10, CATHERINE ROBERT10 & PATRICK WINCKER10 GTC Sequencing Center:DOUGLAS R. SMITH11, LYNN DOUCETTE-STAMM11, MARC RUBEN

16、FIELD11, KEITH WEINSTOCK11, HONG MEI LEE11 & JOANN DUBOIS11 Department of Genome Analysis, Institute of Molecular Biotechnology:ANDR ROSENTHAL12, MATTHIAS PLATZER12, GERALD NYAKATURA12, STEFAN TAUDIEN12 & ANDREAS RUMP12 Beijing Genomics Institute/Human Genome Center:HUANMING YANG13, JUN YU13, JIAN W

17、ANG13, GUYANG HUANG14 & JUN GU15 Multimegabase Sequencing Center, The Institute for Systems Biology:LEROY HOOD16, LEE ROWEN16, ANUP MADAN16 & SHIZEN QIN16 Stanford Genome Technology Center:RONALD W. DAVIS17, NANCY A. FEDERSPIEL17, A. PIA ABOLA17 & MICHAEL J. PROCTOR17 Stanford Human Genome Center:RI

18、CHARD M. MYERS18, JEREMY SCHMUTZ18, MARK DICKSON18, JANE GRIMWOOD18 & DAVID R. COX18 University of Washington Genome Center:MAYNARD V. OLSON19, RAJINDER KAUL19 & CHRISTOPHER RAYMOND19 Department of Molecular Biology, Keio University School of Medicine:NOBUYOSHI SHIMIZU20, KAZUHIKO KAWASAKI20 & SHINS

19、EI MINOSHIMA20 University of Texas Southwestern Medical Center at Dallas:GLEN A. EVANS21?, MARIA ATHANASIOU21 & ROGER SCHULTZ21 University of Oklahomas Advanced Center for Genome Technology:BRUCE A. ROE22, FENG CHEN22 & HUAQIN PAN22 Max Planck Institute for Molecular Genetics:JULIANE RAMSER23, HANS

20、LEHRACH23 & RICHARD REINHARDT23 Cold Spring Harbor Laboratory, Lita Annenberg Hazen Genome Center:W. RICHARD MCCOMBIE24, MELISSA DE LA BASTIDE24 & NEILAY DEDHIA24 GBFGerman Research Centre for Biotechnology:HELMUT BL?CKER25, KLAUS HORNISCHER25 & GABRIELE NORDSIEK25 18 The Sequence of the Human Genom

21、e PDF J. Craig Venter, Mark D. Adams, Eugene W. Myers, Peter W. Li, Richard J. Mural, Granger G. Sutton, Hamilton O. Smith, Mark Yandell, Cheryl A. Evans, Robert A. Holt, Jeannine D. Gocayne, Peter Amanatides, Richard M. Ballew, Daniel H. Huson, Jennifer Russo Wortman, Qing Zhang, Chinnappa D. Kodir

22、a, Xiangqun H. Zheng, Lin Chen, Marian Skupski, Gangadharan Subramanian, Paul D. Thomas, Jinghui Zhang, George L. Gabor Miklos, Catherine Nelson, Samuel Broder, Andrew G. Clark,4 Joe Nadeau, Victor A. McKusick, Norton Zinder, Arnold J. Levine, Richard J. Roberts,8 Mel Simon, Carolyn Slayman, Michael

23、 Hunkapiller, Randall Bolanos, Arthur Delcher, Ian Dew, Daniel Fasulo, Michael Flanigan, Liliana Florea, Aaron Halpern, Sridhar Hannenhalli, Saul Kravitz, Samuel Levy, Clark Mobarry, Knut Reinert, Karin Remington, Jane Abu-Threideh, Ellen Beasley, Kendra Biddick, Vivien Bonazzi, Rhonda Brandon, Mich

24、ele Cargill, Ishwar handramouliswaran, Rosane Charlab, Kabir Chaturvedi, Zuoming Deng, Valentina Di Francesco, Patrick Dunn, Karen Eilbeck, Carlos Evangelista, Andrei E. Gabrielian, Weiniu Gan, Wangmao Ge, Fangcheng Gong, Zhiping Gu, Ping Guan, Thomas J. Heiman, Maureen E. Higgins, Rui-Ru Ji, Zhaoxi

25、 Ke, Karen A. Ketchum, Zhongwu Lai, Yiding Lei, Zhenya Li, Jiayin Li, Yong Liang, Xiaoying Lin, Fu Lu, Gennady V. Merkulov, Natalia Milshina, Helen M. Moore, Ashwinikumar K Naik, Vaibhav A. Narayan, Beena Neelam, Deborah Nusskern, Douglas B. Rusch, Steven Salzberg, Wei Shao, Bixiong Shue, Jingtao Su

26、n, Zhen Yuan Wang, Aihui Wang, Xin Wang, Jian Wang, Ming-Hui Wei, Ron Wides, Chunlin Xiao, Chunhua Yan, Alison Yao, Jane Ye, Ming Zhan, Weiqing Zhang, Hongyu Zhang, Qi Zhao, Liansheng Zheng, Fei Zhong, Wenyan Zhong, Shiaoping C. Zhu, Shaying Zhao, Dennis Gilbert, Suzanna Baumhueter, Gene Spier, Chri

27、stine Carter, Anibal Cravchik, Trevor Woodage, Feroze Ali, Huijin An, Aderonke Awe, Danita Baldwin, Holly Baden, Mary Barnstead, Ian Barrow, Karen eeson, Dana Busam, Amy Carver, Angela Center, Ming Lai Cheng, Liz Curry, Steve Danaher, Lionel Davenport, Raymond Desilets, Susanne Dietz, Kristina Dodso

28、n, Lisa Doup, Steven Ferriera, Neha Garg, Andres Gluecksmann, Brit Hart, Jason Haynes, Charles Haynes, Cheryl Heiner, Suzanne Hladun, Damon Hostin, Jarrett Houck, Timothy Howland, Chinyere Ibegwam, Jeffery Johnson, Francis Kalush, Lesley Kline, Shashi Koduru, Amy Love, Felecia Mann, David May, Steve

29、n McCawley, Tina McIntosh, Ivy McMullen, Mee Moy, Linda Moy, Brian Murphy, Keith Nelson, Cynthia Pfannkoch, Eric Pratts, Vinita Puri, Hina Qureshi, Matthew Reardon, Robert Rodriguez, Yu-Hui Rogers, Deanna Romblad, Bob Ruhfel, Richard Scott, Cynthia Sitter, Michelle Smallwood, rin Stewart, Renee Stro

30、ng, Ellen Suh, Reginald Thomas, Ni Ni Tint, Sukyee Tse, Claire Vech, Gary Wang, Jeremy Wetter, Sherita Williams, Monica Williams, Sandra Windsor, Emily Winn-Deen, Keriellen Wolfe, Jayshree Zaveri, Karena Zaveri, Josep F. Abril,4 Roderic Guig,4 Michael J. Campbell, Kimmen V. Sjolander, Brian Karlak,

31、Anish Kejariwal, Huaiyu Mi, Betty Lazareva, Thomas Hatton, Apurva Narechania, Karen Diemer, Anushya Muruganujan, Nan Guo, Shinji Sato, Vineet Bafna, Sorin Istrail, Ross Lippert, Russell Schwartz, Brian Walenz, Shibu Yooseph, David Allen, Anand Basu, James Baxendale, Louis Blick, Marcelo Caminha, Joh

32、n Carnes-Stine, Parris Caulk, Yen-Hui Chiang, My Coyne, Carl Dahlke, Anne Deslattes Mays, Maria Dombroski, Michael Donnelly, Dale Ely, Shiva Esparham, Carl Fosler, Harold Gire, Stephen Glanowski, Kenneth Glasser, Anna Glodek, Mark Gorokhov, Ken Graham, Barry Gropman, Michael Harris, Jeremy Heil, Sco

33、tt Henderson, Jeffrey Hoover, Donald Jennings, Catherine Jordan, James Jordan, John Kasha, Leonid Kagan, Cheryl Kraft, Alexander Levitsky, Mark Lewis, Xiangjun Liu, John Lopez, Daniel Ma, William Majoros, Joe McDaniel, Sean Murphy, Matthew Newman, Trung Nguyen, Ngoc Nguyen, Marc Nodell, Sue Pan, Jim

34、 Peck, Marshall Peterson, William Rowe, Robert Sanders, John Scott, Michael Simpson, Thomas Smith, Arlan Sprague, Timothy Stockwell, Russell Turner, Eli Venter, Mei Wang, Meiyuan Wen, David Wu, Mitchell Wu, Ashley Xia, Ali Zandieh, Xiaohong Zhu 19ID PSPPF1 standard; RNA; PLN; 1523 BP.AC Y12618;SV Y1

35、2618.1DT 30-JUN-1997 (Rel. 52, Created)DT 02-FEB-1999 (Rel. 58, Last updated, Version 4)DE Pisum sativum mRNA for PPF-1 proteinKW ppf-1 gene; PPF-1 protein.OS Pisum sativum (pea)OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;OC euphyllophytes; Spermatophyta; Magnoliophyta; eudi

36、cotyledons;OC core eudicots; Rosidae; eurosids I; Fabales; Fabaceae; Papilionoideae;OC Pisum.RN 1RA Zhu Y., Zhang Y., Luo J., Davies P.J., Ho D.T.H.;RT PPF-1, a post-floral-specific gene expressed in short-day-grown G2 pea,RT may be important for its never-senescing phenotype;RL Gene 208:1-6(1998).R

37、N 3RP 1-1523RA Zhang Y.;RT ;RL Submitted (02-FEB-1999) to the EMBL/GenBank/DDBJ databases.RL Y. Zhang, Peking University, Box 28, College of Life Sciences, Beijing,RL 100871, PRCDR Demeter; Y12618; Y12618.DR MENDEL; 14275; Pissa;2332;14275.DR SPTREMBL; O04699; O04699.FH Key Location/QualifiersFHFT s

38、ource 1.1523FT /db_xref=taxon:3888FT /organism=Pisum sativumFT /strain=G2FT /dev_stage=pre-floral seedlingsFT /tissue_type=apical budFT /clone_lib=lambda ZAPIIFT CDS 48.1376FT /db_xref=SPTREMBL:O04699FT /gene=ppf-1FT /product=PPF-1 proteinFT /protein_id=CAA73179.1FT /translation=MAKTLISSPSFLGTPLPSLH

39、RTFSPNRTRLFTKVQFSFHQLPPIQFT SVSHSVDLSGIFARAEGLLYTLADATVAADAAASTDVAAQKNGGWFGFISDGMEFVLKVFT LKDGLSSVHVPYSYGFAIILLTVIVKAATLPLTKQQVESTLAMQNLQPKIKAIQERYAGFT NQERIQLETSRLYTQAGVNPLAGCLPTLATIPVWIGLYQALSNVANEGLLTEGFLWIPSFT LGGPTSIAARQSGSGISWLFPFVDGHPLLGWYDTAAYLVLPVLLIVSQYVSMEIMKPPQFT TNDPNQKNTLLIFKFLPLMIGYFS

40、LSVPSGLTIYWFTNNVLSTAQQVWLRKLGGAKPAVFT NENAGGIITAGQAKRSASKPEKGGERFRQLKEEEKKKKLIKALPVEEVQPLASASASNDFT GSDVENNKEQEVTEESNTSKVSQEVQSFSRERRSKRSKRKPVASQ Sequence 1523 BP; 421 A; 325 C; 311 G; 466 T; 0 other; ctcaagcctt caagcctgaa gcgtctcgta cacaaacctt ctcatccatg gcgaagacac 60 tgatttcttc tccatcattc ctcggtac

41、tc cacttccttc acttcaccgt actttctccc 120 ctaatcgcac caggcttttc accaaagttc aattcagttt ccaccaactt cctccgattc 180 . . . . . . ggaccacata catttgtttg tagtttatag taagttttgt atatgtcaaa cagtttgtat 1440 catttttggg ttgacaattt tattgaacat gttatttaat catgcaaaat atcttttgtt 1500 tcatttaagt tccacatgtt agc 1523/20212

42、223SWISS-PROT: TXH1_SELHU (P56676)HUWENTOXIN-I (HWTX-I). Chinese bird spider). DISULFID 2-17 9-22 16- 29 24編號：U00096名稱：Escherichia coli菌株： K-12 MG1655基因數：4293個堿基數：4639221 bp25生物信息的開發和應用以核酸蛋白質等生物大分子為主要研究對象以信息、數理、計算機科學為主要研究手段以計算機網絡為主要研究環境以計算機軟件為主要研究工具對序列數據進行存儲、管理、注釋、加工對各種數據庫進行查詢、搜索、比較、分析構建各種類型的專用數據庫信息

43、系統研究開發面向生物學家的新一代計算機軟件26生物信息學研究利用數理統計、模式識別、動態規劃、密碼解讀、語意解析、信令傳遞、神經網絡、遺傳算法以及隱馬氏模型等各種方法對序列、結構數據進行定性和定量分析，從中獲取基因編碼、基因調控、序列-結構-功能關系等理性知識闡明細胞、器官和個體的發生、發育、病變、衰亡的基本規律和時空聯系探索生命起源、生物進化、生命本質等重大理論問題，最終建立“生物學周期表”27生物信息學 研究方向基因組序列裝配基因識別基因功能預報基因多態性分析基因進化mRNA結構預測基因芯片設計基因芯片數據分析疾病相關基因分析蛋白質序列分析蛋白質家族分類蛋白質結構預測蛋白質折疊研究代謝途徑

44、分析轉錄調控機制蛋白質芯片設計蛋白質芯片數據分析藥物設計2829引自Neil Campbell著Biology第4版,996生物進化30“Daday, where Im from?”“Mum, why Im different from Sally?”31 Discovery can not be waited! 世界上每分鐘有10個兒童死于營養不良 每小時有11個美國人死于用藥不當 愛茲病毒每天在一個病人身上擴增一億倍32實驗生物學計算生物學理論生物學33國際著名生物信息中心Bioinformatics CentresNCBI National Center for Biotechnolog

45、y Information (US) EBI European Bioinformatics Institute (EU) HGMP Human Genome Mapping Project Resource Centre (UK )ExPASy Expert of Protein Analysis System (Switzerland )CMBI Centre of Molecular and Biomolecule (The Netherlands)ANGIS National Genome Information Service (Australia) NIG National Ins

46、titute of Genetics (Japan)BIC National Bioinformatics Centre (Singapore)34歐洲分子生物學網絡組織 (EMBnet)European Molecular Biology NetworkEMBnet為國際著名生物信息學組織，為世界各國提供生物信息資源，并合作進行生物信息的研究、開發、應用和人才培訓。35EMBnet國家節點歐洲: 奧地利、比利時、丹麥、法國、芬蘭 、德國、希臘 匈牙利、愛爾蘭、以色列、意大利、挪威、 波蘭、葡萄牙、斯洛伐克、西班牙、瑞典、瑞士、荷蘭、土耳其、英國亞洲: 中國、印度 澳洲: 澳大利亞北美洲: 加

47、拿大 非洲：南非南美洲: 阿根廷、古巴、智利、墨西哥36亞太生物信息學網絡組織中國節點37生物技術和信息技術是21世紀的兩大經濟發展支柱，生物信息學是生命科學和信息科學的結合點，是當今自然科學新的前沿領域。生物信息資源建設是生物信息研究開發的基礎。1996年，北京大學加入歐洲分子生物學網絡組織，成為該組織的中國國家節點，并成立生物信息中心，為生物、醫學、制藥、農業、環境等領域的研究開發提供生物信息資源服務，并開展二次數據庫構建、軟件集成、基因組分析等研究。歐洲分子生物學網絡組織中國國家節點National NodeEuropean Molecular Biology Network北京大學生物

48、信息中心Centre of Bioinformatics Peking University383940數據庫查詢數據庫搜索文件下載網絡教程網絡新聞序列分析序列裝配分子模型結構分析藥物設計412000年CBI主服務器頁面訪問量42安裝了70多個數據庫，提供200多種軟件下載建立了14個國外著名生物信息中心鏡象提供了數據庫和文獻查詢、搜索構建了中華民族基因多樣性等專用數據庫集成和開發了基于Web的生物信息軟件工具開展了分子模擬、序列分析等應用研究舉辦了國際國內培訓班、講習班、討論會開設了生物信息學概論研究生課程434445中華民族基因多樣性數據庫轉錄因子細胞特異性數據庫Cytomer蛋白質結構域

49、數據庫Domain蛋白質回環數據庫Loop水稻矮縮病毒數據庫RDV二硫鍵信息數據庫Bridge構建二次數據庫46中華民族基因多態性數據庫47水稻矮縮病毒基因組數據庫48轉錄因子細胞特異表達數據庫49蛋白質回環數據庫50蛋白質二硫鍵數據庫廖黔寧，羅靜初，周培愛，顧孝誠，梁宋平，虎紋捕鳥蛛毒素-I突變體的設計、合成和活性鑒定，中國生物化學和分子生物學學報,5(5):756-761, 1999年。SY Lu, PC Deng, XC Liu, JC Luo, RS Han, XC Gu，SP Liang, XC Wang, F Li, V Lozanov, A Patthy and S Pongor

50、, Solution structure of the Major a-amylase inhibitor of the crop plant amaranth，J. Biol. Chem. 274 (29):20473-20478, 1999. 51525354擬南芥突變體庫數據庫北大耶魯合作項目55Computer Aided Vaccine Design SystemDatabaseArticlesLab WorkAlgorithm(ANN),Analysis Program,Adjust ProgramData FlowRight/Wrong?Right/Wrong?AnswerAnswer56生物信息學應用研究 分子模型Liu Y, Luo J, Xu C, Ren F, Peng C, Wu G, Zhao J, Purification, char