从基本粒子到生物圈

1、Introduction to Bioinformatics1Half day on the web,half month in the lab.saves you- Alan Bleasby201011000AGAGGAAA2000年2月2日，北京大学燕北园300多位教师的家用计算机接入Internet；2001年2月12日，北京大学2000多个本科生宿舍的计算机接入Internet.BioMedXBioinformatics7/13/20223网络时代的生命科学和生物技术产业讨论会9-10 Apr 2001首届中国生物信息学大会11-13 Apr 20014引自J Postlethwait

2、 & J Hopson著The Nature of Life，1989从基本粒子到生物圈5引自Neil Campbell著Biology第4版，1996生物界病毒细菌6植物细胞动物细胞引自Neil Campbell著Biology第4版，19967引自Neil Campbell著Biology第4版，1996细胞分裂8人类23对染色体9DNA-遗传密码的携带者10引自Neil Campbell著Biology第4版，199611引自Neil Campbell著Biology第4版,1996胰岛素蛋白酶蜘蛛毒素光合作用受体金属硫蛋白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拟南芥Thermotoga maritimaEscherichia coli大肠杆菌Buchnerasp. APSRickettsia prowazekiiUreaplasma urealyticumBacillus subtilisDrosophila melanogasterThermoplasma acidoph

6、ilumPlasmodium falciparumHelicobacter pylori mouseCaenorhabitis elegansratBorrelia burgorferiBorrelia burgorferiAquifex aeolicusNeisseria meningitidis Z2491Mycobacterium tuberculosis 16图片引自数据引自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编号：U00096名称：Escherichia coli菌株： K-12 MG1655基因数：4293个碱基数：4639221 bp25生物信息的开发和应用以核酸蛋白质等生物大分子为主要研究对象以信息、数理、计算机科学为主要研究手段以计算机网络为主要研究环境以计算机软件为主要研究工具对序列数据进行存储、管理、注释、加工对各种数据库进行查询、搜索、比较、分析构建各种类型的专用数据库信息

43、系统研究开发面向生物学家的新一代计算机软件26生物信息学研究利用数理统计、模式识别、动态规划、密码解读、语意解析、信令传递、神经网络、遗传算法以及隐马氏模型等各种方法对序列、结构数据进行定性和定量分析，从中获取基因编码、基因调控、序列-结构-功能关系等理性知识阐明细胞、器官和个体的发生、发育、病变、衰亡的基本规律和时空联系探索生命起源、生物进化、生命本质等重大理论问题，最终建立“生物学周期表”27生物信息学 研究方向基因组序列装配基因识别基因功能预报基因多态性分析基因进化mRNA结构预测基因芯片设计基因芯片数据分析疾病相关基因分析蛋白质序列分析蛋白质家族分类蛋白质结构预测蛋白质折叠研究代谢途径

44、分析转录调控机制蛋白质芯片设计蛋白质芯片数据分析药物设计2829引自Neil Campbell著Biology第4版,996生物进化30“Daday, where Im from?”“Mum, why Im different from Sally?”31 Discovery can not be waited! 世界上每分钟有10个儿童死于营养不良 每小时有11个美国人死于用药不当 爱兹病毒每天在一个病人身上扩增一亿倍32实验生物学计算生物学理论生物学33国际著名生物信息中心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欧洲分子生物学网络组织 (EMBnet)European Molecular Biology NetworkEMBnet为国际著名生物信息学组织，为世界各国提供生物信息资源，并合作进行生物信息的研究、开发、应用和人才培训。35EMBnet国家节点欧洲: 奥地利、比利时、丹麦、法国、芬兰 、德国、希腊 匈牙利、爱尔兰、以色列、意大利、挪威、 波兰、葡萄牙、斯洛伐克、西班牙、瑞典、瑞士、荷兰、土耳其、英国亚洲: 中国、印度 澳洲: 澳大利亚北美洲: 加

47、拿大 非洲：南非南美洲: 阿根廷、古巴、智利、墨西哥36亚太生物信息学网络组织中国节点37生物技术和信息技术是21世纪的两大经济发展支柱，生物信息学是生命科学和信息科学的结合点，是当今自然科学新的前沿领域。生物信息资源建设是生物信息研究开发的基础。1996年，北京大学加入欧洲分子生物学网络组织，成为该组织的中国国家节点，并成立生物信息中心，为生物、医学、制药、农业、环境等领域的研究开发提供生物信息资源服务，并开展二次数据库构建、软件集成、基因组分析等研究。欧洲分子生物学网络组织中国国家节点National NodeEuropean Molecular Biology Network北京大学生物

48、信息中心Centre of Bioinformatics Peking University383940数据库查询数据库搜索文件下载网络教程网络新闻序列分析序列装配分子模型结构分析药物设计412000年CBI主服务器页面访问量42安装了70多个数据库，提供200多种软件下载建立了14个国外著名生物信息中心镜象提供了数据库和文献查询、搜索构建了中华民族基因多样性等专用数据库集成和开发了基于Web的生物信息软件工具开展了分子模拟、序列分析等应用研究举办了国际国内培训班、讲习班、讨论会开设了生物信息学概论研究生课程434445中华民族基因多样性数据库转录因子细胞特异性数据库Cytomer蛋白质结构域

49、数据库Domain蛋白质回环数据库Loop水稻矮缩病毒数据库RDV二硫键信息数据库Bridge构建二次数据库46中华民族基因多态性数据库47水稻矮缩病毒基因组数据库48转录因子细胞特异表达数据库49蛋白质回环数据库50蛋白质二硫键数据库廖黔宁，罗静初，周培爱，顾孝诚，梁宋平，虎纹捕鸟蛛毒素-I突变体的设计、合成和活性鉴定，中国生物化学和分子生物学学报,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拟南芥突变体库数据库北大耶鲁合作项目55Computer Aided Vaccine Design SystemDatabaseArticlesLab WorkAlgorithm(ANN),Analysis Program,Adjust ProgramData FlowRight/Wrong?Right/Wrong?AnswerAnswer56生物信息学应用研究 分子模型Liu Y, Luo J, Xu C, Ren F, Peng C, Wu G, Zhao J, Purification, char