Prof. of crop genetics and breeding Department of Agronomy College of Agriculture and Biotechnology, Zhejiang University

Transkriptio

1 Bioinformatics Longjiang Fan ( 樊龙江 ) Prof. of crop genetics and breeding Department of Agronomy College of Agriculture and Biotechnology, Zhejiang University Prof. of bioinformatics James D. Watson Institute of Genome Sciences, Zhejiang University Institute of Bioinformatics, Zhejiang University The Bioinplant Lab (Bioinformatics and Plant Genomics Lab)

2 Contents LE C # TOPICS DETAILS TEACHER 1 Historical introduction Functional genomics QTL/LD mapping etc. ZHU 2 Network analysis Microarray, proteomic analysis, pathway analysis ZHU 3 Sequence alignment 4 Sequence pattern 5 Genome analysis 6 Evolutionary analysis Sequence collection; alignment and database searching for similar sequences Domain finding; pattern and functional element finding, etc. Annotation, transcriptomic analysis, comparative genomics Genetic variation and phylogenetic analysis FAN FAN FAN FAN 7 Practice 8 Course activities Utility and realization of bioinformatics tools and databases) References reading, case study and discussion/ Invited speeches QIU/FAN FAN

3 Grading Mini tests during the course Term paper

4 Readings Bioinformatics----Sequence and Genome Analysis (D.W. Mount, Cold Spring Harbor Lab Press, 2004) 生物信息学札记 ( 第 3 版 )( 樊龙江,PDF,Online Course: ) 生物信息学手册 ( 第 2 版 )( 郝柏林, 张淑誉, 上海科技出版社,2002) Developing Bioinformatics Computer Skills (C. Gibas and P. Jambeck, O REILLY, 2001) Nucleic Acids Research Database Issue (Jan. 1, from 1993) Program Issue (July 1, from 2003)

5 Google bioinformatics

6 1. Historical Introduction and Overview 1.1 What s bioinformatics? 1.2 Bioinformatics milestones

7 Bioinformatics is the science of using information to understand biology. It s s the discipline of obtaining information about genomic or protein sequence data. This may involve similarity searches of databases, comparing your unidentified sequence to the sequences 1.1 What s in a database, Bioinformatics or making predictions? about the sequence based on current knowledge of similar sequences. A A term coined in 1990 to define the use of computers in sequence analysis (Claverie, 2000)

8 Bioinformatics is a branch of biological science which deals with the study of methods for storing, retrieving and analyzing biological data, such as nucleic acid (DNA/RNA) and protein sequence, structure, function, pathways and genetic interactions. It generates new knowledge that is useful in such fields as drug design and development of new software tools to create that knowledge. Bioinformatics also deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, structural biology, software engineering, data mining, image processing, modeling and simulation, discrete mathematics, control and system theory, circuit theory, and statistics. Major research areas: Sequence analysis Genome annotation Computational evolutionary biology Literature analysis Analysis of gene expression Analysis of regulation Analysis of protein expression Wikipedia_bioinformatics Analysis of mutations in cancer Comparative genomics Modeling biological systems High-throughput image analysis Structural bioinformatic approaches Prediction of protein structure Molecular Interaction Docking algorithms

9 Role of bioinformatics Control and management of the high-through data Analysis of primary data e.g. Base calling from chromatograms Mass spectra analysis DNA microarrays images analysis Statistics Database storage and access Results analysis in a biological context

10 Example of high-throughput Complete genome sequencing (Sanger and highthroughput sequencing etc.) Large-scale sampling of the transcriptome (EST, small RNA populations) Simultaneous expression analysis of thousands of genes (DNA microarrays, SAGE) Large-scale sampling of the proteome Protein-protein analysis large-scale 2-hybrid (yeast, worm) Large-scale 3D structure production (yeast) Metabolism modelling Simulations Biodiversity

11 Illumina 公司先后推出的高通量测序仪测序通量 ( 能力 ) 增长情况 (2010/4/15) A:HiSeq 2000 B:Genome Analyzer Ⅱx C:Genome Analyzer Ⅱe C A B

12 Bioinformatics: Genome-driven! A thaliana Rice In 1983 and 1984 HGP Meetings supported by NIH and DOE

13 An International Crop & Livestock Genomics Campaign For The Future Throughput Building: More Machines Efficient Process Powerful Computing Versatile Strategies Systematic Analysis worm ALL major pests and pathogens aphidall other farmed plant sp. grasshopper Tough weeds Invertebrate ABC Med. Herds Vertebrate ABC Marine species Mammal ABC pines Garden vari. Primate ABC bee poplarmajor tree sp. chimp cattle sheep Major crop species zebrafish frog turtle Solanaceae XYZ mouse rat cotton potato Rosaceae XYZ A. thal human pig wheat barley Leguminosae XYZ fruitfly rice corn B. nap soy tomato Graminae XYZ Jun Yu, 2002

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16 The massive quantities of data generated by genomic research have given rise to the field of bioinformatics--an emerging discipline that seeks to integrate computer science with applications derived from molecular biology. We are swimming in a rapidly rising sea of data...how do we keep from drowning? Roos DS. Bioinformatics----Trying to swin in a sea of data. Science, 2001,291(5507):

17 CACTAGTCTCTGTACTAGCCACTAGAAGTACTAACCTTTCACACTAATATATCTATCTCCTGCTGCATTTAGTACACAAGTTCATAAAAGCACCCTATTTCTATAAAAAAAATACGGTAAATGTAGCAACTTAC TAGTACCATAAGAAATTTTGCTGATCTAGCTAACTTATTACTAGCTACTTGCTAGGTCTGAACACTATTAAAATGTAACAATACACTTACCTCCTTGATCTGTGCAGCCCTGTTCTCACGCTGGCTTCTATGG TGCGAGTAGTATTCCTAGGTTTTCGTAGGCTTTTATAGCAACAGCTTTCTTCGGACCGAATGAGACACCTGCCTTGTTTATGAGAGGGATGGATAGCTTTCACCTGCTGGACATTTATTTGTTTTTTTTTACT GGTCACTACATTCCTATCCACTGGTGCATATCTATCCTATCCCCTTTGGTCAGTAAAATATACTGCCTCCCCCATTCTCTTTCTTTCTCTATCTTTCTCTAAGCTTAACACACTTTAAGTTCACAAAATTATTAT TATTATTATTATTATTATTATTATTATTATTATTATTATTATTATTATTATTATTATTATTATTAGCAGGCTTCCCTCCTTTAGAAATTTCATCGTCGAAATTATTATACCTTGGTGATGGAAAAACTGAGGCTAGT TTTTTCTGGAGATCATCTTCCTTCTCCCATGTGGCCTCATCCATGGTGTGATGACTCCATTGTACCTTTAAAAATCTAATTGTTTGGTTCCTTGTTTTTAGATCTTTAATATCCAAGATACAAACAGGATATTC CTGATATGTCAAATCGTTATGCAACTCAGCCATAGGAATTTCAACTTAATCACTTGGCCTCCGAAGGCATTTACGAAGCATGGAGATGTGGAATACATCATGTACCCCGGTGAAAGCATCTGGTAGCTTTA GCATGTAAGGCACTTCTCCTATTTGCTTAACAATTGTAAATGGTCCAACATATCTGGAACTTATTTTTTTTCCAAGTCCGAATCGCTTAATTCCCTTTATAGGTGATACTTTTAAATATACCCAGTCACCTATAT CAAAGTTAAGATCCCTTCTCCTATTATCTGCATAACTTTTTTTGTCTATTTTGAGCTGTTTGCAGTCGTTCCCGTATCAGTCGTATTGTTTCTTCTATCTGTTGTATTATATCCGGTCCTAACAATTTTCTTTCTC CTACTTCGTTCCAGCAAACAGGTGTTCTGCATTTCCTTCCATATAAGGCTTCATACGGAGCCATTTGTATACTAGATTGATAACTATTGTTATATGCAAATTCTGCTAATGGCATAAATTCTTTCCATGATCCT TTAAATTCTAGGATGCAAGATCGTAAAATATTTTCAATTATTTGATTCACCCTTTCAGTTTGTCCATCGGTTTGGGGGTGATACGCTGCACTGAAATCTAATGTTGTTCCCACGGGCTTGTGTAGTCTTTTCT AGAAATTGGACAGAAACTGTGTATCTCTGTCTGACACAATCCTTCTTGGAACACCATGTAAAGATACTATTTCTTTGACATATAGTTTAGCTAACCTTTCCAAAGAAAATTTGCTTTTAACGGGTATGAAATGA GCAGATTTTGTTAACCGATCCACTATTCAGATACTATCATTTCCTGGAGGTGTGGTAGGTAATCCTTGAACAAAGTCCATACTGATTTCTTCTCATTTCCATAGTGGAATACTTAAGGGTTGTAACAGTCTTG CCGGCCTTTGATGTTCAACTTTTACGCATTGGCAGATATCACATTCTGCAATGAATTTTGCAATTTCTATTTTCATGATACATTTTGGTACTTCCTGGATGTATGGTATAGGGAGAGAAATGTGATTCTTCCAA TATTCTCTGTTTTAAATTAGGGTCGTTAGGCACACACAATCTATTTTTGAAACATATAGCACCATTATGATCAATTCGAAATTCAGACACCTTCCCTTCTTCAATATTTTTCTTTGCCTTTTGCAATCCACTGTC GTCTCTTTGTTTCTCTAGAATATTTTCTTCTAAAGTAGGCTTTATTTGAAGCACGGGTAATAATACTCTGGGTTCATGGATCTTTAATTCCACATCCAATCTTTCCAAGTCTCTAAGTATATGTTGATCCTGTGT GATCTGAATAGCCATATTACAAAGAGCTTTTCGACTTAGAGCATCTTCCACAATGTTGGCTTTCAGAGGGTGATAATGAATATTCAAATCATAATCTTTCAATAATTCTAACCATCCCCTTTATCTCATATTCA ATTCCTTCTGAGTAAATATGTACTTTAAACTTTTGTGGTCAGTAAATATTTCACAATGCTCACCATATAGGTAATGTCTCCAGATTTTTAAGGCAAAAATAACAGCAGCTAATTCCATATCATGGGTTGGATAA TTTTGCTCGTATGGCTTTAATTGACGCGAAGCATAGGCAATTACCTTAGCTTTTTGCATGAGAACACAACCTAATCCAATTTTTGAAGCATCACAGTAAATAGTAAATTCTTCTCCCATTATAGGCAAGGCAA GAATAGTAAATTCTTTGCAATTCTGAGTCCACTCATATTTTACTCCCTTTTGTGTCAACCGGGTTAGAGGAGCTGCAATTCTAGCGAAGTTACTAATAAATCGACGGTAATATCCCGCCAACCCAAGAAAAC TTCGTATCTCGGTTACCGATGAGGGCCTTTTCCACTCTGAGACGGTTTTGACCTTTTCAGGGTCCACTGATATACCTTCACCCGAAATAACATGACCAAGCAAAAATACTTTATCCATCCAGAAATCGCATT TCTTTAATTTGGCAAATAGTTTATGATCTCGCAATGTCTTGTAGTACTATTCTCAAATGATTTGCATGATCTTCCTTAGTCTTGGAATATATCAAAATATCATCTATATATAAATACAACTACAAATTAATCAAGA TAAGGCTTGAATTTACGATTCATTAAATCCATAAAAGCTGCCGGTGCATTAGTCAAACCAAATGGCATTACTAGATATTCATAGTGTCCATAGCATGCACGGAAAGCAGTCTTGGGTATATCACTAGGTTTA ATCTTTAGTTGATGGTAGCCTGATTGAAGATCAATTTTTGAGAAAACCCGAGCTCCTTGTAGTTGATCAAATAGATCGTCTATCCTTGGTAAAGGATATTTGTTTTTGATAGTCACCTTATTCAGTTCTCGGTA ATCCGTGCATAATCGCATAGTTCCATCCTTTTTCTTGACAAATAGAACAGGAACACCCCCACGGGGAGACACTAGGACAAATGAATCCTTTATCTTCTAATTCTTTTAATTGTACATTTAGTTCCTTTAGCTC AACAGGGGCCATTATGTAGGGTGCCTAATAAATCGGAGTAGTTCCTGGTCCTATTTCAATACCAAATTCAATCTCTCGATCTAGTGCTAATCCTGGTAATTCAGCTGGAAAAACTGGAAACTCATTCACAAT TGGCATTCCTTCCCAACTTGCTTCCTTTCTCATGATTTCTGCCACTAAAGGTCTTGGTAAATTGTTTTAATCTCCATGGTAAGTAATTTGGTTTTGATCCCATGGTTTAAGTGTAATTTGTTTTTCATGGCAATC AATATTTGCTTTGTTCTTACATAACCAATCCATACCAAGTATAATATCAAAATCATGCATATCCAAGGGTATGAGGTCAGCAGTTAATTCCCATCCATCAATAGTAATTGGACACAATTTGCAAATTAAATTAG TTATTTGGCTATCCAAAGGAGTTTCTATGCAAATCCTTTCTTTTAATTGACTAGTAGGGATGGTGTATTTTCTCACGAAGTTGGTGGAGATAAACGAATGTGTTGCGCCAGAATCAAATAAAACTTTACCAGG ATAAGAGCACACTAAGACATTACCTGTAACCACGGTGTTGGATTTTTCGGCTGTGCTCTTAGTTAAGTTGTATACCCCAAGCGCGATTCCCACCTTGTGAATTATTCGACCGTATTCCTCATGTAGTATTAG TATTTGCAGGTGGCTTTCCTTGATTTGGCCCATTATTATTTGCTGAAGATGGTCCAGGTAAATAAAGCGACGGTACTGAAGTCAATACTTTAGTACTTGGCTGAGTAGTTCAATTAACTCGATTTTTACCCTT CTGTAACAGAGGACAAAGGTATCTAGTATGTCCTGCTTCTCCACACTCAAAGCACCTTCCCCACCGATTAGGACAAATTGATGGAACATGGCCACCTTGGCATATTGGACATTTTCTGTCTTGATTTTCTAA AGATTCCCTCTACATTTTTCCAGAGTAGTTTCCACGGAATCTTCCCTGGTTTTGTTGATTATTTGTCTTGAATTTCTTTTGGGGTTGTCCGTGTTCTATTCTTTGTTCATGATACCCCTTCTCAAGAAGTTGTG CTTTACTTACTACCTCCCTGAATATGGTTAATTCAAAGGCTTCGACACACCTTTTGAGAGGTTGGCGTAATCCACTTTCAAATCGTCGAGCTTTAGAGCCGTCCGTTTGTACAAATTCAGGAGCAAATCTTG CAAGTCTCGAAAATTCTATTTCATATTCTACTACAGATTTATTACCTTACTTAAGCTCTAGAAATTCCTTCTTCATTCTCTTCACACTTTCTGGAAAATATTTCTTGTAAAAAGCTTCTTTGAATATTTCCCATGT AATAGAGATACGTTCCGAATATGACTTTTTGTGAGCATCCCACCATTCAAAAGCACTAGACTGAAGCATATAGGTAGCATATGTAATCTTTTCTTTATCTGTACAACCCATAGCTTCAAATGCCTTTTCCATT GCTACTATCCAAACTTCCGCTTCAAGTGGATTGGTAGTTCCTGAAAGGAAAAAGTATGAATTACCCCCTGAACTATTGCGAGAGTATGAATTACCCCCCCCCCCCAAAACCACAAAACCAGACATATTAAAC CTCAAACTATTGAAATCGGATTACCCCCCCTGATTCAATCCGGAGCGGTTTGGTCCTACGTGGCATACACGTGGCACCGCCATGGAAATCCAATCAGCAATATTAGGTGGTCCCACATGTCATGATCATGT ATTTCTTCCACTTTCCCCTCTCTTCATCTCCTCCAGGGCAAATAGAAAGCGGCGCGGTGGTGGCGCTCTCCAGGGCGGCCGGGGGAAGCGGCGGCGGCGGCGTCCAGGGCGGGTGGGGGAAGCGGC GGCGTCCAGGGCGGCTGCGGAAGCGACGGCGGCGTCCAGGGTGGGCTAGGGAAGCGGCGGCTTCTAGGGCAAGCTGGGGAAGTGGCGGCGGTGGCGGCGACGGCGGCGTCCAGGGCGGGCTGG GGAAGCAGCGGCGTCCAGGGCAGGCGGGGAAGTGGCGGTGATGACGGCGCCCTCCAGGTCGAACTGGGGTGGTGGCGGGGAAGTGACGGCAGCGACGGCGCCCTCCAGGGCAGGTAGGGGAAGC GGTGGCGGCGGGTGTGGCGGGAGCGCTCGTGCGGTGGGCGCGGCGGGAGCGGGAGCGGGCGCGGCGAGGAGCAGGCGCTTGTGCTCCTCCTCCGTGGCGCCAGAGATGGAGCGGGCGCTCGTG AGCGGGTCGGCCGCCGCTGCGAGCTCGCCGTGGAGGCGGCGAGAATCGAGATCGACGGCGAGCTCCACGGAGATGGAGAGAAGAAGGGAAGGGGCAAAGAGGAGGGGGAGAAGAGGAGGGTTGG GCAGACAGTGGGCCCCACCATATTTATTTGTTGTGGCTGACAAGTGGGTCCTATATATTTTTCTTTTGTTTTAGCTGACCAGACTGCCACATGGGCATCCACGTAGGACCGAAACCACCCTATATCGATCTA GGGGGTAATTCATCCGGTTTGTAAAGTTCAGGGTTAAAAATAACTGGTATTGGAGTTCAGGGTTAAAAATCGGACGACCGTAATTGTTGAGGGGGTAATTCGTACTTTTTCCTTCTTGAAAATGTTGGTGG CTTCAATTTCTGAAATTCCCCAAGTCCATTCCGGTTAGCATCACTTTTAGTAGTACGTTCTAAAATCTCCATCTATCGTTGTTGGGTTTCCTGTTGCTTGCCCAATATATTCGCGAGTAAGTTAGCCCAAGGG TCTTGACTACTTGCACTAGGTATTATTGATCCAGTGGCACCATTACTAGTATTATTTCCATCCTGACTAGTACCATTGTTGTCGTTGTTTTGCTCCATCTATCATATTCAACTCATTAGCCAGAATACATAAAT GATCATTGGATGGATCTCAAAATGGTAACAAAAATCAGATTTACTATAAAATATTCAATATAGGTAATATTAAAATAAAACTATTTAGTTATATTATCATCATTATACTTTTCTCTTCTTATTTTAGTCTTATCATT ATTCTTAACATGCACCAGTTAAAAAATAAATAAATAAAATTAGTACAAACCACAAGCACCACAGCACTAGTGCATTACGGTCATGTTTAGATTCAAATTTTTTTCTTCAAACTTCTAACTTTTCCGTCACATCAA ATGTTTGGACACATGCATGGAGCATTAAATGTGGAGAAAAAAACAATTGCACAGTTTGCATGTAAATTGTGAGACGAATCTTTTGAGCCTAATTACACCATGATTTGACAATGTGATGCTATAGTAAACATTT GTTAATGATAGATTAATTAGTCTTAATAAATTCATCTCGCAGTTTACAGGTGAAATCTGTAATTTGTTTTGTTATTAGTCTACATTTAATACTTCAAATGTATATCCATATACTTGAAAAAAAATTTGGCACACG AACTAAACACAGCCTACTTCGACGAAAAGAAAGTGCAGGAGCCTATCATGCTACACAAACACTAAGGCAAACACCTACTGGTGTACTAGTGCCACATACAGAGCTCTGGTTGTTTACACAAGATGTCTAGA AAGACATCACCATGAGTTCTGATGTTAACTCTTCAGTTCTAAAAGCTCCTTTGGCTGTCTCGTGACCCATCCACACATGCTACTAACACTAAGGGTGTGTAGGGTGTGTTTAGTTCACACCAAAATTGAAAG TTTGGTTGAAATTGAAACGATGTGACGGAAAAGTTGAAGTTTACGTGTGTAGGAGAGTTTTGATGTGATGAAAAAGTTAAAAGTTTGAAGAAAAATTTTGGAACTAAACTCAGCCTAAAGGACTTATTATAGT GGAGTACATCCCATCCCAAGGGAAAACAAAACCCATACTGACACCACTCCTACATCTCACACACTGCCACTAGAGCTGTCACTACCCCCAACCCCACTCTGCAGAACAGTAAATGGTTTCACTCAGGTAG CAGACGCGGTGGTACAGGCGATAGGTGAGGCGCTCCAGAAACATAGGCTGTGTTTAGATGGTGGAAAAGTTGGGAGGTTGGGAGAAAGTTAGTAGTTTGGAGAAAAAGTTGGTAGTTTATGTGTGTACG AAAGTTTTCGATGTGATGTGATGTGATGGAAAGTTAGGAATTTGGGGGGAACTAAACACGGCCATAACTTCATTCTCACTGGAGCGAACAATAGTCGGCAGTTATTTTTATATACATATTTGTTAAAGAAGA AATATTACTGTCCATGGATATTAATGGCCGATAAATAGTATAAAAAACATTAAATATAGTAAGTGATTTAAATACATTCTGCAGAGGTATTAAAATAATTGTCATAATCTCGTTCCTTCAATCCATTTTTTTCCA ACTAGTGATACCTCATCTGAGAATCACGGCGCCGAATTCCCTACTTGTGTGAGGCATTCCTTCTCTCACACTGATATCAGCCGACCCGATATCGTTGTTTCAGGTATCGGCCGTCTCAGGCTAAGTATCAA AATCATGTTCCATGATTATGACGTTATTATTCTCACTGATAAAATCATCAATCAATTATTCGGGAGTTAATAATATTTACCGTTAGATCGTTAGTATCATCATCCCAATATATAATACAGGTAAGCGAATTTAGT TAGAGATGATTAAGTAAAATAGTTGATGGACACAGTCTTGCCTTCTCTTTTGTTGTTCTTCCTCTGCATCCCACCTAATCAAATATACATGTCTTTGGTATTAATTTATATCTATATTTGTTATGCAGGACATTA GCTACTGGAACCAGCTACTAGGACCATAGATAGCTAGTTGATGTGACTCTACTGGAGAAAGAAAACCAACATGTAGGCCTAGTTTATTTCCCCCAAAATTTTTCCCAAAAACATCACATTGAATCTTTGGAC ATATGCATGGAGCATTAAATATAGATTAAAAAAACTAATTGCACAGTTAGGGGGAAAATCACGAGACGAATCTTTTGAGCCTTATTAATCCATGATTAGCCATAAGTGCTACAGTAATGCCAGCTGGGCGAG GAGAGGTGGCAGTGGTGGTGAGCCCAGCTGGGTGGATGTGTGGAGGGTGGAGAGGAGACGGGGAGGGAGGGAGGGAGGGAGAGAGGACTAGG

18 Genome Analysis Genome Analysis 基因组分析 簊圁組奮橀

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20 Expression data Non-coding gene finding Genomewide comparison Genomewide SNP analysis

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22 Bioinformatics and Computational Biology Strictly speaking, bioinformatics is a subset of the large field of computational biology, the application of quantitative analytical techniques in modeling biological system. (Gibas and Jambeck, 2001) From Bioinformatics to Computational Biology (Claverie, 2000)

23 Bioinformatics and Systems biology Systems biology is a biology-based interdisciplinary field of study that focuses on complex interactions within biological systems, using a more holistic perspective (holism instead of the more traditional reductionism) approach to biological and biomedical research.

24 Genomics and Its Sons Improve Health And Design Better Crops TOXICOGENOMICS PHARMACOGENOMICS Link Networks In A Background of Organisms PHYSIOGENOMICS STRUCTURAL GENOMICS PROTEOMICS Define Cellular Processes Into Systematic Networks Map Gene Products To Cellular Processes Map Genes And Their Expression Identify Genes And Other Elements Determine Genome Sequence FUNCTINAL GENOMICS Bioinformatics GENOMICS Jun Yu, 2002

25 History of Bioinformatics

26 Key developments in bioinformatics (by D.W. Mount, Bioinformatics---Sequence and Genome Analysis, Second edition, 2004) The first sequences to be collected were those of proteins (M. Dayhoff) DNA sequence databases date from the early 1980s (W. Goad) Sequences can be easily retrieved from public databases (D. Lipman) Sequence alignment programs have proliferated The dot matrix or diagram method for comparing sequences (A.J. Gibbs and G.A. McIntyre, 1970) Alignment of sequences by dynamic programming (S.B. Needleman and C.D. Wunsch, 1970) Finding local alignments between sequences (T. Smith and M. Waterman, 1981) Multiple sequence alignment

27 There are several methods for predicting RNA secondary structure Evolutionary relationships are discovered using sequences Database searches for similar sequences can reveal gene function FASTA and BLAST enable rapid database searches (B. Pearson and S. Altschul) Protein sequences can be predicted by translation of DNA sequences Protein structure can be predicted The first complete genome sequence was H. influenzae AceDB was the first genome database Genome analysis methods are being developed Gene expression analysis is done using microarrays Data storage and mining technologies are used for large biological data sets Sequence analysis can be automated using Bioperl and the internet

28 Bioinformatics milestones 1996 Yeast genome completely sequenced 1997 PSI-BLAST 1998 Worm (multicellular) genome completely sequenced 1999 Fly genome completely sequenced

29 1956 美国召开首次生物学中的信息理论研讨会 1962 Pauling 提出分子进化理论 1965 Dayhoff 构建世界上第一个蛋白质序列数据库 1970 Needleman-Wunsch 算法被提出 1977 Staden 利用计算机软件分析 DNA 序列 1981 Smith-Waterman 算法出现 1981 序列模序 / 模体 (motif) 的概念被提出 (Doolittle) 1982 GenBank 数据库 (Release3) 公开 1982 λ- 噬菌体基因组被测序 1983 Wilbur 和 Lipman 提出序列数据库的搜索算法 (Wilber- Lipman 算法 ) 1985 快速序列相似性搜索程序 FASTP/FASTN 发布 1988 美国家生物技术信息中心 (NCBI) 创立 1988 欧洲分子生物学网络 EMBnet 创立 三大核酸数据库 (GenBank EMBL 和 DDBJ) 开始国际合作

30 图 年美国田纳西首次生物学中的信息理论研讨会论文集 (Yockey H P, Platzman, Quastler H. Symposium on information theory in biology. Gatlinburg Tennessee, New York: Pergamon Press,1958)

31 1990 快速序列相似性搜索程序 BLAST 发布 1991 表达序列标签 (EST) 概念被提出, 从此开创 EST 测序 1993 英国 Sanger 中心在英国休斯顿 (Hinxton) 建立 1994 欧洲生物信息学研究所在英国休斯顿成立 1995 第一个细菌基因组测序完成 1996 酶母基因组测序完成 1997 PSI-BLAST(BLAST 系列程序之一 ) 发布 1998 Phil Green 等人研制的自动测序组装系统 Phred-Phrap- Consed 系统正式发布 1998 多细胞线虫基因组测序完成 1999 果蝇基因组测序完成 2000 人类基因组测序基本完成 2000 拟南芥基因组测序完成 2001 人类基因组初步分析结果公布 2002 水稻基因组测序完成 * 主要引自美国家生物信息中心 (NCBI)Education-Bioinformatics Milestone(2000), 原文截止至 1999 年果蝇基因组测序完成, 有关人类基因组 PhilGreen 等的自动测序组装系统和三大核酸数据库的合并等内容为作者补入

32 纵观生物信息学的发展历史, 可分为 4 个主要阶段 : History of bioinformatics: Four stages: the emergence ( ); the initial stage (1980s); genome sequencing (1990-) and high-throughput sequencing (2005-) (1) 萌芽期 (60-70 年代 ): 以 Dayhoff 的替换矩阵和 Neelleman- Wunsch 算法为代表, 它们实际组成了生物信息学的一个最基本的内容和思路 : 序列比较 它们的出现, 代表了生物信息学的诞生 ( 虽然 生物信息学 一词很晚才出现 ) ; (2) 形成期 (80 年代 ): 以分子数据库和 FASTA 等相似性搜索程序为代表 在这一阶段, 生物信息学作为一个新兴学科已经形成, 并确立了自身学科的特征和地位 ; (3) 基因组测序时代 (90 年代 - 至今 ): 以模式基因组测序与 BLAST 为代表 ; (4) 高通量测序时代 (2005-): 以第二代测序技术和基因组重测序为代表