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Bioinformatics, Computational Biology — An Introduction 1 “…the most wondrous map ever produced by mankind” — Bill Clinton 2 3 DNA 4 Post Genome Era Why small variation, BIG DIFFERENCE? The difference between you & chimp is ~1.24% The difference between you and Maggie is ~0.1% 5 Genetics: From DNA to population Source: gsk 6 7 Introduction – Gene History 1865 Mendel: The basic unit of inheritance is a gene. Mendel’s work was forgotten until 1900s. 1944 The gene was known to be made of DNA (Deoxyribonucleic Acid). 1953 James Watson and Francis Crick : Double helical structure of DNA. (雙股螺旋) 8 Introduction – Gene History (Cont.) 1990 The Human Genome Project (人類基 因體計畫 ) started. 1995 The first free-living organism to be sequenced : haemophilus influenzae (流行性感冒嗜血桿菌) 1998 CELERA joined the gene research. 2000 The human DNA sequence draft was completed (published in 2001). 9 動物細胞(細胞核、細胞質、細胞膜) DNA位於細胞核內之「核仁」 10 DNA Sequence 11 DNA Length The total length of the human DNA is about 3109 (30億) base pairs. 1% ~ 1.5% of DNA sequence is useful. # of human genes: 30,000~40,000 Conclusion from the human genome project Expected # is 100,000 originally. 12 13 DNA Double Helix (雙股螺旋） 14 DNA/RNA 核甘酸分子 核甘酸(Nucleotide)包含： - 五碳糖(去氧核糖, deoxyribose) 磷酸基(phosphate group) 四種含氮鹼基之一(A、G、C、T/U) 15 Backbone of DNA and RNA 16 Watson-Crick Base Pairs 17 DNA Double Helix (雙股螺旋） 18 From DNA to RNA to Protein 19 Biochemical Context of Genomics and Proteomics DNA Genome “Genomics” mRNA Proteins Proteome “Proteomics” Cell functions 20 What is Bioinformatics? Deduction of knowledge by computer analysis of biological data See 988000 pages on this issue on the WWW Information stored in the genetic code (DNA), protein sequences Protein 3D structures, chromosome structure Protein interaction, transcription factor, motif Micro array gene expression, functional MRI, 2D-gel Experimental results Patient statistics Scientific literature Analysis tools 21 Computational Biology & Bioinformatics Computational Biology Biological Hypothesis Formal Specifications Raw Data Algorithms ___ Bioinformatics Information End with Experiments 22 Key Strategy for Analysis In Biology In Computer Sciences Evolution Information Consensus Clustering Sequences FESS Structures Distance Measurement Functions Data 23 Key Strategy for System Biology Experiment Computer Aided Design Specification, Simulation and Reverse Engineering Reverse Engineering Strategy Hypothesis Simulation Results 重 新 假 設 n 實際Microarray 輸出結果 Match y Candidate Set 再作 Distinguishable 實驗 是否唯一吻合 是 Believe it or not 否 22 24 Problems on Different Levels 25 Some Problems in Bioinformatics Sequence comparison Longest common subsequence Edit distance Similarity Multiple sequence alignment Fragment assembly of DNA sequences Shortest common superstring Physical mapping Double digest problem Consecutive ones problem Evolutionary trees Molecular structure prediction Protein folding 26 Bioinformatics and Computer Science Algorithm: all computing problems. Image processing: 3D images of RNA folds or protein. Database: massive database and retrieval. Distributed system and parallel processing: massive storage and accelerating computation. 27 Conclusion Biology easily has 500 years of exciting problems to work on. -- Donald E. Knuth 28 Go working for Integrating Nano Cognition Biology Informatics ! Reference – Journals Bioinfomatics (SCI) Bulletin of Mathematical Biology (SCI) Computer Applications in the Biosciences Journal of Computational Biology (SCI expanded) Journal of Mathematical Biology (SCI) Journal of Molecular Biology (SCI) Nucleic Acids Research (SCI) Gene (SCI) Science (SCI) 30 Reference – Web Sites BioWeb http://bioweb.uwlax.edu/ MIT Biology Hypertextbook http://esgwww.mit.edu:8001/esgbio/ Bioinformatics Related Journals http://www.iscb.org/journals.html NCBI http://www.ncbi.nlm.nih.gov/ 31