1 / 64

CS 177 Introduction to Bioinformatics Fall 2004

CS 177 Introduction to Bioinformatics Fall 2004. Instructor: Anna Panchenko ( panch@ncbi.nlm.nih.gov ) Instructor: Tom Madej ( madej@ncbi.nlm.nih.gov ) Co-Instructor: Rahul Simha ( simha@gwu.edu ). Lecture 1: Introduction Instructors Course goals Grading policy Motivating problem

juliewilliams
Download Presentation

CS 177 Introduction to Bioinformatics Fall 2004

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CS 177 Introduction to BioinformaticsFall 2004 • Instructor: Anna Panchenko (panch@ncbi.nlm.nih.gov) • Instructor: Tom Madej (madej@ncbi.nlm.nih.gov) • Co-Instructor: Rahul Simha (simha@gwu.edu)

  2. Lecture 1: Introduction Instructors Course goals Grading policy Motivating problem Course overview Molecular basis of cellular processes Historical timeline

  3. Course Goals • The student will be introduced to the fundamental problems and methods of bioinformatics. • The student will become thoroughly familiar with on-line public bioinformatics databases and their available software tools. • The student will acquire a background knowledge of biological systems so as to be able to interpret the results of database searches, etc. • The student will also acquire a general understanding of how important bioinformatics algorithms/software tools work, and how the databases are organized.

  4. Grading Policy • Homework: 50%, weekly assignments • Final exam: 50% “All examinations, papers, and other graded work products and assignments are to be completed in conformance with: The GeorgeWashington University Code of AcademicIntegrity”.

  5. Optional Texts P.E. Bourne and H. Weissig (2003), Structural Bioinformatics, Wiley & Sons.

  6. What is Bioinformatics? • A merger of biology, computer science, and information technology. • Enables the discovery of new biological insights and unifying principles. • Born from necessity, because of the massive amount of information required to describe biological organisms and processes.

  7. Severe Acute Respiratory Syndrome (SARS) • SARS is a respiratory illness caused by a previously unrecognized coronavirus; first appeared in Southern China in Nov. 2002. • Between Nov. 2002 and July 2003, there were 8,098 cases worldwide and 774 fatalities (WHO). • The global outbreak was over by late July 2003. A few new cases have arisen sporadically since then in China. • There is currently no vaccine or cure available.

  8. Fig. 2 from Rota et al.

  9. Phylogenetic analysis of coronavirus proteins Fig. 2 from Rota et al.

  10. Conserved motifs in coronavirus S proteins. Fig. 2 from Rota et al.

  11. Exercise! Look up the SARS genome on the NCBI website: www.ncbi.nlm.nih.gov

  12. OMIM PubMed PubMed Central 3D Domains Journals Structure Books CDD/CDART Entrez Taxonomy Protein Genome GEO/GDS UniSTS UniGene Nucleotide SNP PopSet The(ever expanding)Entrez System

  13. Course Overview Lecture 1: Introduction Instructors Grading policy Motivating problem Course overview Molecular basis of cellular processes Historical timeline

  14. Lecture 2: General principles of DNA/RNA structure and stability • Physico-chemical properties of nucleic acids • RNA folding and structure prediction • Gene identification • Genome analysis • Lecture 3: General principles of protein structure and stability • Physico-chemical properties of proteins • Prediction of protein secondary structure • Protein domains and prediction of domain boundaries • Protein structure-function relationships

  15. Lecture 4: Sequence alignment algorithms • The alignment problem • Pairwise sequence alignment algorithms • Multiple sequence alignment algorithms • Sequence profiles and profile alignment methods • Alignment statistics

  16. Lecture 5: Computational aspects of protein structure, part I • Protein folding problem • Problem of protein structure prediction • Homology modeling • Protein design • Prediction of functionally important sites • Lecture 6: Computational aspects of protein structure, part II • Structure-structure alignment algorithms • Significance of structure-structure similarity • Protein structure classification

  17. Lecture 7: Bioinformatics databases • Sequence and sequence alignment formats, data exchange • Public sequence databases • Sequence retrieval and examples • Public protein structure databases • Lab exercises • Lecture 8: Bioinformatics database search tools • Sequence database search tools • Structure database search tools • Assessment of results, ROC analysis • Lab exercises

  18. Lecture 9: Phylogenetic analysis, part I • Molecular basis of evolution • Taxonomy and phylogenetics • Phylogenetic trees and phylogenetic inference • Software tools for phylogenetic analysis • Lecture 10: Phylogenetic analysis, part II • Accuracies and statistical tests of phylogenetic trees • Genome comparisons • Protein structure evolution

  19. Lecture 11: Experimental techniques for macromolecular analysis • Sequencing, PCR • Protein crystallography • Mass spectroscopy • Microarrays • RNA interference

  20. Lecture 12: Systems biology • Genomic circuits • Modeling complex integrated circuits • Protein-protein interaction • Metabolic networks Lectures 13, 14: To be decided…

  21. Molecular Biology Background • Cells – general structure/organization • Molecules – that make up cells • Cellular processes – what makes the cell alive

  22. Two Cell Organizations • Prokaryotes – lack nucleus, simpler internal structure, generally quite smaller • Eukaryotes – with nucleus (containing DNA) and various organelles

  23. Selected organelles… • Nucleus – contains chromosomes/DNA • Mitochondria – generate energy for the cell, contains mitochrondrial DNA • Ribosomes – where translation from mRNA to proteins take place (protein synthesis machinery) • Lysosomes – where protein degradation takes place

  24. Cells can become specialized…

  25. Three domains of life • Prokarya Bacteria Archaea • Eukarya Eukaryotes

  26. Universal phylogenetic tree. Fig. 1 from: N.R. Pace, Science276 (1997) 734-740.

  27. Molecules in the cell • Proteins – catalyze reactions, form structures, control membrane permeability, cell signaling, recognize/bind other molecules, control gene function • Nucleic acids – DNA and RNA; encode information about proteins • Lipids – make up biomembranes • Carbohydrates – energy sources, energy storage, constituents of nucleic acids and surface membranes • Other small molecules – e.g. ATP, water, ions, etc.

  28. The Central Dogma of Molecular Biology

  29. Exercise! Retrieve a protein structure from the SARS coronavirus from the NCBI website; you can use: www.ncbi.nlm.nih.gov/Structure/ Look at the structure for the SARS protease using Cn3D.

  30. Timeline 1859 Darwin publishes On the Origin of Species… 1865 Mendel’s experiments with peas show that hereditary traits are passed on to offspring in discrete units. 1869 Meischer isolates DNA. 1895 Rőntgen discovers X-rays. 1902 Sutton proposes the chromosome theory of heredity.

  31. Timeline (cont.) 1911 Morgan and co-workers establish the chromosome theory of heredity, working with fruit flies. 1943 Astbury observes the first X-ray pattern of DNA. 1944 Avery, MacLeod, and McCarty show that DNA transmits heritable traits (not proteins!). 1951 Pauling and Corey predict the structure of the alpha-helix and beta-sheet.

  32. Timeline (cont.) 1953 Watson and Crick propose the double helix model for DNA based on X-ray data from Franklin and Wilkins. 1955 Sanger announces the sequence of the first protein to be analyzed, bovine insulin. 1955 Kornberg and co-workers isolate the enzyme DNA polymerase (used for copying DNA, e.g. in PCR). 1958 The first integrated circuit is constructed by Kilby at Texas Instruments.

  33. Timeline (cont.) 1960 Perutz and Kendrew obtain the first X-ray structures of proteins (hemoglobin and myoglobin). 1961 Brenner, Jacob, and Meselson discover that mRNA transmits the information from the DNA in the nucleus to the cytoplasm. 1965 Dayhoff starts the Atlas of Protein Sequence and Structure. 1966 Nirenberg, Khorana, Ochoa and colleagues crack the genetic code! 1970 The Needleman-Wunsch algorithm for sequence comparison is published.

  34. Timeline (cont.) 1972 Dayhoff develops the Protein Sequence Database (PSD). 1972 Berg and colleagues create the first recombinant DNA molecule. 1973 Cohen invents DNA cloning. 1975 Sanger and others (Maxam, Gilbert) invent rapid DNA sequencing methods.

  35. Timeline (cont.) 1980 The first complete gene sequence for an organism (Bacteriophage FX174) is published. The genome consists of 5,386 bases coding 9 proteins. 1981 The Smith-Waterman algorithm for sequence alignment is published. 1981 IBM introduces its Personal Computer to the market. 1982 The GenBank sequence database is created at Los Alamos National Laboratory.

  36. Timeline (cont.) 1983 Mullis and co-workers describe the PCR reaction. 1985 The FASTP algorithm is published by Lipman and Pearson. 1986 The SWISS-PROT database is created. 1986 The Human Genome Initiative is announced by DOE. 1988 The National Center for Biotechnology Information (NCBI) is established at the National Library of Medicine in Bethesda.

  37. Timeline (cont.) 1992 Human Genome Systems, in Gaithersburg, MD, is founded by Haseltine. 1992 The Institute for Genomic Research (TIGR) is established by Venter in Rockville, MD. 1995 The Haemophilus influenzea genome is sequenced (1.8 Mb). 1996 Affymetrix produces the first commercial DNA chips.

  38. Timeline (cont.) 1988 The FASTA algorithm for sequence comparison is published by Pearson and Lipman. 1990 Official launch of the Human Genome Project. 1990 The BLAST program by Altschul et al., is published. 1991 The CERN research institute in Geneva announces the creation of the protocols which make up the World Wide Web.

  39. Timeline (cont.) 1996 The yeast genome is sequenced; the first complete eukaryotic genome. 1996 Human DNA sequencing begins. 1997 The E. coli genome is sequenced (4.6 Mb, approx. 4k genes). 1998 The C. elegans genome is sequenced (97 Mb, approx. 20k genes); the first genome of a multicellular organism.

  40. Timeline (cont.) 1998 Venter founds Celera in Rockville, MD. 1998 The Swiss Institute of Bioinformatics is established in Geneva. 1999 The HGP completes the first human chromosome (no. 22). 2000 The Drosophila genome is completed.

  41. Timeline (cont.) 2000 Human chromosome no. 21 is completed. 2001 A draft of the entire human genome (3,000 Mb) is published. 2003 The Human Genome is “completed”! Approx. 30,000 genes (estimated).

More Related