Transcript lecture1_16
Introduction to Bioinformatics Lecturer: Prof. Yael Mandel-Gutfreund Teaching Assistance: Rachelly Normand Olga Karinski Course web site : http://webcourse.cs.technion.ac.il/236523 What is Bioinformatics? 2 Course Objectives • To introduce the bioinfomatics discipline • To make the students familiar with the major biological questions which can be addressed by bioinformatics tools • To introduce the major tools used for sequence and structure analysis and explain in general how they work (limitation etc..) 3 Course Structure and Requirements 1.Class Structure 1. 2. 2 hours lecture 1 hour tutorial 2. Home work • Homework assignments will be given every second week • The homework will be done in pairs. • 4/4 homework assignments will be submitted 2. A final project will be conducted in pairs * Project will be presented as a poster –poster day 9.3 4 Grading • 20 % Homework assignments • 80 % final project (10% proposal, 20% supervisor evaluation 70% poster presentation) 5 What is Bioinformatics? 6 What is Bioinformatics? “The field of science in which biology, computer science, and information technology merge to form a single discipline” Ultimate goal: to enable the discovery of new biological insights as well as to create a global perspective from which unifying principles in biology can be discerned. 7 Central Paradigm in Molecular Biology Gene (DNA) mRNA Protein 21ST centaury Genome Transcriptome Proteome 8 From DNA to Genome Watson and Crick DNA model 1955 1960 1965 1970 1975 1980 1985 9 1990 First genome Hemophilus Influenzae 1995 Yeast genome 2000 First human genome draft Total complete genomes 15.10.15 = 21,636 10 21000 genomes… What’s Next ? The “post-genomics” era Annotation Comparative genomics Functional genomics Systems Biology Main Goal: To understand the living cell 11 And beyond… Personalized medicine 12 From ….21000 genomes To…Understanding living cells Annotation CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA TAT GGA CAA TTG GTT TCT TCT CTG AAT ...... .............. TGAAAAACGTA 14 Identify the genes within a given sequence of DNA Identify the sites Which regulate the gene Annotation Predict the function What do they do??? 15 How do we identify a new gene in a genome? A gene is characterized by several features (promoter, ORF…) some are easier and some harder to detect… 16 Using Bioinformatics approaches for Gene hunting Relative easy in simple organisms (e.g. bacteria) Still VERY HARD for higher organism (e.g. humans) 17 Comparative genomics 18 Perhaps not surprising!!! How humans are chimps? Comparison between the full drafts of the human and chimp genomes revealed that they differ only by 1.23% How can we be so similar--and yet so different? 19 Where are we different ?? Where are we similar ??? VERY DIFFERENT VERY SIMAILAR Conserved between many organisms 20 Sometime minor changes in critical genes can make a big difference Human ATAGCGGGGGGATGCGGGCCCTATACCC Chimp ATAGGGGGGATGCGGGCCCTATACCC Mouse ATAGCGGGATGCGGCGCTATACCA Human ATAGCGGGGGGATGCGGGCCCTATACCC Chimp ATAGGGG--GGATGCGGGCCCTATACCC Mouse ATAGCG---GGATGCGGCGC-TATACC-A 21 Single change in a genes among humans can be responsible for sever diseases Sickle Cell Anemia Due to 1 swapping of an A for a T Image source: http://www.cc.nih.gov/ccc/ccnews/nov99/ 22 Healthy Individual >gi|28302128|ref|NM_000518.4| Homo sapiens hemoglobin, beta (HBB), mRNA ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTGA GGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGC AGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATG CTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGC TCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGAT CCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCA CCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCA CTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACT GGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC >gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens] EEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG MVHLTP AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN ALAHKYH 23 Diseased Individual >gi|28302128|ref|NM_000518.4| Homo sapiens hemoglobin, beta (HBB), mRNA ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTGA GGTGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGC AGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATG CTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGC TCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGAT CCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCA CCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCA CTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACT GGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC >gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens] VEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG MVHLTP AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN ALAHKYH 24 Functional genomics 25 TO BE IS NOT ENOUGH )(תאי גזע עובריים Expressed )(תאים ממוינים Not Expressed 26 The difference in the brain size between Human and apes is mainly related to the different levels of the genes expression and not their content Systems Biology 28 Biological networks Jeong et al. Nature 411, 41 - 42 (2001) What can we learn from Biological Networks What can we learn about this protein • Is the protein essential for the organism ? • Is it a good drug targets? How can bioinformatics contribute to Medicine? http://www.tedmed.com/talks/show?id=17961 31 What of all this will we learn in the course? The course will concentrate on the bioinformatics tools and databases which are used to : - Annotate genes, - Compare genes and genomes - Infer the function of the genes and proteins - Analyze the interactions between genes and proteins ETC…. 32 What of all this will we learn in the course? 1. Introduction to bioinformatics 2. Pairwise alignment 3. Database search 4. Protein alignments 5. MSA and phylogenetic analysis 6. Sequencing 7. Motif search-function prediction 8. Gene expression 9. Structural bioinformatics (proteins and RNA) 10. Biological networks 33