1. Algorithms for Biological Sequence Analysis Kun-Mao Chao ( 趙坤茂 ) Department of Computer Science and Information Engineering National Taiwan University, Taiwan Date: September 14, 2009 WWW: http://www.csie.ntu.edu.tw/~kmchao

2. 2 About this course Course: Algorithms for biological sequence analysis Some basic knowledge on algorithm development and program design is required. We will be focused on the sequence-related algorithmic problems. Genomic sequences are our main target. –The oldest language –The largest program Fall semester, 2009 13:20 – 16:20 Monday, 107 CSIE Building. 3 credits Web site: http://www.csie.ntu.edu.tw/~kmchao/seq09fallhttp://www.csie.ntu.edu.tw/~kmchao/seq09fall

3. 3 Coursework: Homework assignments and Class participation (15%) Two midterm exams (60%; 30% each): –October 26, 2009 (tentatively) –December 7, 2009 (tentatively) Oral presentation of selected papers (25%)

4. 4 Outlines Part I: Sequence Homology –Introduction to basic algorithmic strategies –Pairwise sequence alignment –Multiple sequence alignment –Chaining algorithms for genomic sequence analysis –Suboptimal alignment –Comparative genomics –Compressed / constrained sequence comparison –Hidden Markov models (the Viterbi algorithm et al.) Part II: Sequence Composition –Maximum-sum and maximum-density segments –SNP and haplotype data analysis –Approximate gapped palindrome –Genome annotation –Other advanced topics

5. 5 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]

6. 6 A Brief History of Genetics (cont’d) 1931 Recombination occurs by crossing over. [Harriet Creighton and Barbara McClintock] 1944 DNA is the genetic material. [Oswald Avery, Colin McLeod and Maclyn McCarty] 1953 DNA is a double helix. [James Watson and Francis Crick] 1961-1967 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

7. 7 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

8. 8 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 1988 EMBnet network for database distributionEMBnet network 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

9. 9 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

10. 10 Milestones of Bioinformatics (cont’d) Human Genome Project (1990-2003)Human Genome Project Mouse 2002 Rat 2004 Chimpanzee 2005 Completed Genomes

11. 11 Chimpanzee Genome

12. 12 The Primate Family Tree Source: Nature

13. 13 A New Book Published by Springer in 2009 (ISBN 978-1848003194) Sequence Comparison: Theory and Methods by Kun-Mao Chao and Louxin Zhang