Welcome to the Bioinformatics Workshop July 28, 2003 Introduction Workshop objectives Module 1: Retrieval of literature dealing with molecular life sciences. Module 2: Sequence databases and similarity searches. Module 3: Protein structure analysis

Workshop logistics Course Website ( /Bioinformaticscourse.html) /Bioinformaticscourse.html Power point presentation In-class workshop

Definition of Bioinformatics Many definitions at the moment: Use of computers to catalog and organize molecular life science information into meaningful entities. Subset of Computational Biology

How can Bioinformatics help make scientific discoveries? Bioinformatics is not just the storage of data in a computer. Bioinformatics is the use of computers to test a biological hypothesis prior to performing the experiment in the laboratory. Bioinformatics is the design of software programs that analyze data.

Basis of molecular biology Hierarchy of relationships (not exactly true): Genome Gene 1Gene 3Gene 2Gene X Protein 1Protein 2Protein 3Protein X Function 1Function 2Function 3Function X

Genome Sizes FERN: 160,000,000,000 LUNGFISH: 139,000,000,000 SALAMANDER: 81,300,000,000 NEWT: 20,600,000,000 ONION: 18,000,000,000 GORILLA: 3,523,200,000 MOUSE: 3,454,200,000 HUMAN: 3,400,000,000 31,000 Drosophila : 137,000,000 13,500 C. elegans 96,000,000 19,000 Yeast 12,000,000 6,315 E. Coli 5,000,000 5,361 Smallest Genome ?????? Genes

What is the approach used to sequence genomes? Divide and conquer Split the genome into fragments Clone into vectors that can accept large fragments: yeast artificial chromosomes (YAC Library) Landmarks within the genome can be obtained using a Sequence Tagged Sites (STS) Sequences of YAC clones are matched with each other. Sequences that overlap form contigs.

History of the Human Genome Project 1953 Watson, Crick DNA structure 1972 Berg, 1st recombinant DNA 1977 Maxam, Gilbert, Sanger sequence DNA 1980 Botstein, Davis, Skolnick White propose to map human genome with RFLPs 1982 Wada proposes to build automated sequencing robots 1984 MRC publishes first large genome Epstein-Barr virus (170 kb) 1985 Sinsheimer hosts meeting to discuss HGP at UCSanta Cruz; Kary Mullis develops PCR 1986 DOE begins genome studies with $5.3 million 1987 Gilbert announces plans to start company to sequence and copyright DNA; Burke, Olson, Carle develop YACs; Donis- Keller publish first map (403 markers)

History of the Human Genome Project (continued) 1987 (cont) Hood produces first automated sequencer; Dupont devolops fluorescent dideoxy- nucleotides 1988 NIH supports the HGP; Watson heads the project and allocates part of the budget to study social and ethical issues 1989 Hood, Olson, Botstein Cantor propose using STS’s to map the human genome 1990 Proposal to sequence 20 Mb in model organism by 2005; Lipman, Myers publish the BLAST algorithm 1991 Venter announces strategy to sequence ESTs. He plans to patent partial cDNAs; Uberbacher develops GRAIL, a gene finding program 1992 Simon develops BACs; US and French teams publish first physical maps of chromosome s; first genetic maps of mouse and human genome published 1993 Collins is named director of NCHGR; revise plan to complete seq of human genome by Venter publishes first sequence of free-living organism: H. influenzae (1.8 Mb); Brown publishes on DNA arrays 1996 Yeast genome is sequenced (S. cerevisiae)

History of the Human Genome Project (continued) 1997 Blattner, Plunket complete E. coli sequence; a capillary sequencing machine is introduced SNP project is initiated; rice genome project is started; Venter creates new company called Celera and proposes to sequence HG within 3 years; C. elegans genome completed 1999 NIH proposes to sequence mouse genome in 3 years; first sequence of chromosome 22 is announced 2000 Celera and others publish Drosphila sequence (180 Mb); human chromosome 21 is completely sequenced; proposal to sequence puffer fish; Arabadopsis sequence is completed 2001 Celera publishes human sequence in Science; the HGP consortium publishes the human sequence in Nature 2003 Completed genomes: 112 Microbial 18 Eukaryotes 1275 Viruses

Public funding vs. Private funding Public-Taxpayers’ money, international effort. Private-Companies that invest money hope to provide access to their information on a fee basis. Celera also allows some free information to small research groups. Both groups published the sequence of the human genome in 2001.

Bioinformatics is Multidisciplinary Computer Science Math Statistics Structural Biology Phylogenetics Drug Design Genomics Molecular Biology

Bioinformatics at CSULA Upper Div. Standing in Biology or Biochem Upper Div. Standing in CS, IS, CE Introduction to Bioinformatics (Chem 434) (offered in Spring ‘04) One course in C/C++ or PERL programming (CIS 283, CS 201) One course in Molec. Biology/Biochem or Chem/Biol 154L (W’04)

How is Bioinformatics Used? Experimental proof is still the “Gold Standard”. Bioinformatics isn’t going to replace lab work anytime soon Bioinformatics is used to help “focus” the experiments of the benchtop scientist

Unknown Function What’s Left To Do? Find out what the rest of the genome does.

What is left to do? Sequence genomes of other organisms Analyze genes to predict function Analyze interactions of gene products- Create genetic networks Start making changes Modify gene expression patterns to make better crops or better medicines Once this is finished, then what?

Increasing levels of complexity Genome (DNA) Transcriptosome (RNA) Proteome (proteins) Metabalome (metabolic pathways)

Primary public domain bioinformatics servers Public Domain Bioinformatics Facilities European Bioinformatics Institute (EBI) United Kingdom National Center For Biotechnology Information (NCBI) United States Genome Net (KEGG & DDBJ) Japan Databases Analysis Tools Databases Analysis Tools Databases Analysis Tools

Literature Databases and NCBI Learning objective- How does one retrieve information on a particular subject? National Center for Biotechnology Information (NCBI) Databases outside of NCBI Retrieval of information

Literature Databases Medline (PubMed) OMIM CSULA Library Other biological databases BIOSIS Agriculture Melvyl (Books at UC Libraries)

NCBI ENTREZ A search engine that provides access and links between various databases ENTREZ PubMed GenBank Protein databases Genomes PopSet Taxonomy OMIM

On-line Mendelian Inheritance of Man (OMIM) A catalog of human genes linked to diseases Began by Victor A. McKusick at Johns Hopkins University A good place to start when you want to know about a certain disease. This database is linked to PubMed, the OMIM Morbid Map The OMIM Gene Map

CSULA and other resources The best way to access articles at Cal State LA is to obtain the exact reference from PubMed. Then search to the CSULA library database for the article: Publishers to search through at the CSULA Library Site: ACS Wiley InterScience IDEAL There are two Website that offers free access to journals: PubMedCentral: BioMedNet:

How to keep up to date on your favorite subject? Set up Cubby. An automatic retrieval system that searches PubMed and deposits the literature citations in your own account (there is no charge). Demonstration of how Cubby works. Requires a login.

Workshop Exercise 1-Retrieve information on a topic from literature databases. Set up Cubby account for yourself.