Algorithms for Biological Sequence Analysis Kun-Mao Chao ( 趙坤茂 ) Department of Computer Science and Information Engineering National Taiwan University, Taiwan Date: October 2, 2007 WWW:

2 About this course Course: Algorithms for biological sequence analysis We will be focused on the sequence-related algorithmic problems. Genomic sequences are our main target. –The oldest language –The largest program Fall semester, 2007 Tuesday 9:10 – 12:10, 107 CSIE Building. 3 credits Web site:

3 Coursework: Homework assignments and Class participation (15%) Two midterm exams (60%; 30% each): –November 6, 2007 (tentatively) –December 18, 2007 (tentatively) Oral presentation of selected papers (25%)

4 Outlines Part I: Sequence Homology –Introduction to genomes –Dynamic programming strategy revisited –Pairwise sequence alignment –Multiple sequence alignment –Chaining algorithms for genomic sequence analysis –Suboptimal alignment –Comparative genomics –Hidden Markov models (the Viterbi algorithm et al.) Part II: Sequence Composition –Maximum-sum and maximum-density segments –SNP and haplotype data analysis –Genome annotation –Other advanced topics

5 A Brief History of Genetics 1859 Darwin publishes The Origin of Species 1865 Genes are particular factors 1871 Discovery of nucleic acid 1903 Chromosomes are hereditary units 1910 Genes lie on chromosomes 1913 Chromosomes are linear arrays of genes 1931 Recombination occurs by crossing over

6 A Brief History of Genetics (cont’d) 1944 DNA is the genetic material 1945 A gene codes for protein 1951 First protein sequence 1953 DNA is a double helix 1961 Genetic code is triplet 1977 Eukaryotic genes are interrupted 1977 DNA can be sequenced 21th Century: Many genomes completely sequenced

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

11 Chimpanzee Genome

12 The Primate Family Tree Source: Nature