A Whirlwind Tour of Bioinformatics Kun-Mao Chao ( 趙坤茂 ) National Taiwan University

2 About this course Course: Introduction to Biomedical Informatics Spring semester, : :10 Monday, 101 CSIE Building. 3 credits Web site: Instructor: Kun-Mao Chao ( 趙坤茂 )Kun-Mao Chao Teaching assistant: Chia-Jung Chang ( 張家榮 ) & Wu- Lung R. Yang ( 楊伍隆 )

3 TA: Chia-Jung Chang ( 張家榮 ) & Wu-Lung R. Yang ( 楊伍隆 ) Chia-JungWu-Lung

4Coursework Homework assignments and Class participation (10%) Two midterm exams (70%; 35% each): –Midterm #1: April 9, 2012 (tentative) –Midterm #2: May 21, 2012 (tentative) Oral presentation of selected papers/projects (20%)

5 The Best? The Cheapest? The BestEntranceThe Cheapest

6 Bio-X? X-Informatics? Bio-XBioinformaticsX-Informatics Source: NIH, Bioinformatics Journal, NPS

7 Interdisciplinary Pioneers Leonardo da Vinci Isaac Newton Archimedes of Syracuse Source: Wikipedia

8 Amphibia, Triphibia Source: Wikipedia, xplanes

9 Band Alignment (Joint work with W. Pearson and W. Miller, 1992) Seq. 1 Seq. 2

10 Alignment in an Arbitrary Region (Joint work with R. C. Hardison and W. Miller, 1993)

11 Aligning Very Similar Sequences (Joint work with J. Zhang, J. Ostell and Webb Miller, 1997)

12 Generalized Global Alignment (Joint work with X. Huang, 2003)

13 Tag SNPs & Haplotype Inference (Joint work with Y.-T. Huang et al., 2006) Yao-Ting HuangTing ChenKui Zhang Chia-Jung ChangKun-Mao Chao

14 Sequence Comparison: Theory and Methods Sequence Comparison: Theory and Methods (Joint work with L. Zhang, 2009) Sequence Comparison: Theory and Methods

15 Bioinformatics for Biologists Edited by Pavel Pevzner and Ron Shamir Cambridge University Press, 2011

16 Bioinformatics for Biologists Edited by Pavel Pevzner and Ron Shamir

17 Bioinformatics for Biologists Edited by Pavel Pevzner and Ron Shamir

18 Central Dogma of Molecular Biology Source:

19 From Genes to Proteins Source:

20 Double Helix Source:

21 A Brief History of Genetics 1859 Charles Darwin published “The Origin of Species.” 1865 Genes are particular factors. [Gregor Mendel] 1869 Discovery of nucleic acid [Friedrich Miescher] 1903 Chromosomes are hereditary units. [Walter Sutton] 1910 Genes lie on chromosomes. [Thomas Hunt Morgan] 1913 Chromosomes are linear arrays of genes. [Alfred Sturtevant] 1931 Recombination occurs by crossing over. [Harriet Creighton and Barbara McClintock]

22 A Brief History of Genetics (cont’d) 1944 DNA is the genetic material. [Oswald Avery, Colin McLeod and Maclyn McCarty] 1953 DNA is a double helix. [James Watson and Francis Crick] Genetic code is triplet. [Marshall Nirenberg, Har Gobind Khorana, Sydney Brenner & Francis Crick] 1977 DNA was sequenced for the first time. [Fred Sanger, Walter Gilbert, and Allan Maxam] 21th Century: Many genomes completely sequenced MIT Open Courseware: BiologyBiology Introduction to Biology7.012 Introduction to Biology

23 Milestones of Bioinformatics 1962 Pauling's theory of molecular evolution 1965 Margaret Dayhoff's Atlas of Protein SequencesMargaret Dayhoff's 1970 Needleman-Wunsch algorithmNeedleman-Wunsch 1977 DNA sequencing and software to analyze it (Staden)Staden 1981 Smith-Waterman algorithm developedSmith-Waterman algorithm 1981 The concept of a sequence motif (Doolittle)Doolittle 1982 GenBank Release 3 made public 1982 Phage lambda genome sequenced

24 Multiple Nobel Laureates

25 Milestones of Bioinformatics (cont’d) 1983 Sequence database searching algorithm (Wilbur- Lipman)Wilbur- Lipman 1985 FASTP/FASTN: fast sequence similarity searchingFASTP/FASTN 1988 National Center for Biotechnology Information (NCBI) created at NIH/NLMNational Center for Biotechnology Information 1990 BLAST: fast sequence similarity searchingBLAST 1991 EST: expressed sequence tag sequencing 1993 Sanger Centre, Hinxton, UKSanger Centre 1994 EMBL European Bioinformatics Institute, Hinxton, UKEMBL European Bioinformatics Institute

26 Milestones of Bioinformatics (cont’d) 1995 First bacterial genomes completely sequencedbacterial genomes 1996 Yeast genome completely sequencedYeast genome completely sequenced 1997 PSI-BLASTPSI-BLAST 1998 Worm (multicellular) genome completely sequencedWorm (multicellular) genome completely sequenced 1999 Fly genome completely sequenced

27 Milestones of Bioinformatics (cont’d) Human Genome Project ( )Human Genome Project Mouse 2002 Rat 2004 Chimpanzee 2005 Completed Genomes

28 Chimpanzee Genome

29 The Primate Family Tree Source: Nature

30 orz’s Sequence Evolution orz (kid) OTZ (adult) Orz (big head) Crz (motorcycle driver) on_ (soldier) or2 (bottom up) oΩ (back high) STO (the other way around) Oroz (me)  the origin?  their evolutionary relationships?  their putative functional relationships?

31Topics Sequencing and genotyping technologies Molecular sequence analysis Recognition of genes and regulatory elements Comparative genomics Gene expression Molecular structural biology Biological networks Systems biology Computational proteomics Molecular evolution Phylogenetic trees Population genetics Medical informatics

32 Bioinformatics Centers National Center for Biotechnology Information (NCBI, NIH): – European Bioinformatics Institute (EBI): – DNA Data Bank of Japan (DDBJ): – UCSC Genome Browser HomeUCSC Genome Browser Home RCSB Protein Data BankRCSB Protein Data Bank

33 Bioinformatics Departments Computational Biology and Bioinformatics, USC Bioinformatics and Systems Biology, UCSD The Broad Institute of MIT and Harvard Computational and Genomic Biology, UC Berkeley Biomedical Informatics Research, Stanford University Comparative Genomics and Bioinformatics, Penn State Penn Center for Bioinformatics Max Planck Institute for Molecular Genetics Bioinformatics and Computational Biology, Iowa State

34 Bioinformatics Journals Bioinformatics Journal of Computational Biology Genome Research Nature Nucleic Acid Research PLoS Computational Biology Science

35 Nature & Science

36 Bioinformatics Conferences The Annual International Conference on Research in Computational Molecular Biology (RECOMB) The Symposium on Intelligent Systems for Molecular Biology (ISMB) The European Conferences on Computational Biology (ECCB)

37 Bioinformatics Books

38 Bioinformatics Community The International Society for Computational Biology (ISCB)ISCB –Senior Scientist Accomplishment AwardSenior Scientist Accomplishment Award

39 10 Steps to Success in Bioinformatics by Webb Miller 1.Become a biologist. 2.Value your number of citations above your number of publications. 3.Collaborate, and do it with great collaborators. 4.Do not expect a warm welcome from everyone. 5.Be a good collaborator. 6.Distribute and maintain software and/or run web servers that you personally continue to use.

40 10 Steps to Success in Bioinformatics by Webb Miller 7.Alternate between working on specific datasets and writing general-purpose software. 8.Write some of your own software. 9.Don't give up. 10.Be excited about your work.