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

2 The Best? The Cheapest? The BestEntranceThe Cheapest

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

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

5 Amphibia, Triphibia Source: Wikipedia, xplanes

My Journey

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

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

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

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

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

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

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

14 Bioinformatics for Biologists Edited by Pavel Pevzner and Ron Shamir

15 Bioinformatics for Biologists Edited by Pavel Pevzner and Ron Shamir

A Brief Introduction

17 Central Dogma of Molecular Biology Source:

18 From Genes to Proteins Source:

19 Double Helix Source:

20 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]

21 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

22 Multiple Nobel Laureates Multiple Nobel Laureates

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 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

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

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

27 Chimpanzee Genome

28 The Primate Family Tree Source: Nature

29Topics 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

30 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

31 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

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

33 Nature & Science

34 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)

35Books

Books (Cont’d) All grading for the 100+ homework problems in the book is automatically done through the popular online bioinformatics education website Rosalind. All problems represent programming challenges with randomized input given to students.Rosalind 36

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

38 Ten 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.

39 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.