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Genomics, Proteomics, and Bioinformatics

Genomics, Proteomics, and Bioinformatics. Biology 224 Instructor: Tom Peavy August 31, 2009. What is bioinformatics?. Interface of biology and computers Analysis of genomes, genes, mRNA and proteins using computer algorithms and computer databases. What is Genomics?.

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Genomics, Proteomics, and Bioinformatics

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  1. Genomics, Proteomics, and Bioinformatics Biology 224 Instructor: Tom Peavy August 31, 2009

  2. What is bioinformatics? • Interface of biology and computers • Analysis of genomes, genes, mRNA and proteins using computer algorithms and computer databases

  3. What is Genomics? What is Proteomics? What is the Transcriptome?

  4. On bioinformatics “Science is about building causal relations between natural phenomena (for instance, between a mutation in a gene and a disease). The development of instruments to increase our capacity to observe natural phenomena has, therefore, played a crucial role in the development of science - the microscope being the paradigmatic example in biology. With the human genome, the natural world takes an unprecedented turn: it is better described as a sequence of symbols. Besides high-throughput machines such as sequencers and DNA chip readers, the computer and the associated software becomes the instrument to observe it, and the discipline of bioinformatics flourishes.” Martin Reese and Roderic Guigó, Genome Biology 2006 7(Suppl I):S1, introducing EGASP, the Encyclopedia of DNA Elements (ENCODE) Genome Annotation Assessment Project

  5. What do you want out of this course?

  6. Themes throughout the course: gene/protein families • Retinol-binding protein 4 (RBP4) • member of the lipocalin family • small, abundant carrier protein We will study it in a variety of contexts including • --homologs in various species • --sequence alignment • --gene expression • --protein structure • --phylogeny

  7. bioinformatics medical informatics public health informatics algorithms databases infrastructure Tool-users Tool-makers

  8. DNA RNA protein phenotype protein sequence databases cDNA ESTs UniGene Microarrays genomic DNA databases

  9. There are three major public DNA databases EMBL GenBank DDBJ Housed at EBI European Bioinformatics Institute Housed at NCBI National Center for Biotechnology Information Housed in Japan

  10. Growth of GenBank Base pairs of DNA (billions) Sequences (millions) 1982 1986 1990 1994 1998 2002 Updated 8-12-04: >40b base pairs Year

  11. Growth of GenBank + Whole Genome Shotgun (1982-November 2008) 250 200 150 Number of sequences in GenBank (millions) Base pairs of DNA in GenBank (billions) Base pairs in GenBank + WGS (billions) 100 50 0 1982 1987 1992 1997 2002 2007

  12. Taxonomy at NCBI: ~200,000 species are represented in GenBank 11/08 http://www.ncbi.nlm.nih.gov/Taxonomy/txstat.cgi

  13. The most sequenced organisms in GenBank Homo sapiens 13.1 billion bases Mus musculus8.4b Rattus norvegicus6.1b Bos taurus 5.2b Zea mays 4.6b Sus scrofa 3.6b Danio rerio3.0b Oryza sativa (japonica)1.5b Strongylocentrotus purpurata 1.4b Nicotiana tabacum 1.1b Updated 11-6-08 GenBank release 168.0 Excluding WGS, organelles, metagenomics

  14. Go to NCBI website http://www.ncbi.nlm.nih.gov/

  15. PubMed is… • National Library of Medicine's search service • 12 million citations in MEDLINE • links to participating online journals • PubMed tutorial (via “Education” on side bar)

  16. Entrez integrates… • the scientific literature; • DNA and protein sequence databases; • 3D protein structure data; • population study data sets; • assemblies of complete genomes

  17. Entrez is a search and retrieval system that integrates NCBI databases

  18. BLAST is… • Basic Local Alignment Search Tool • NCBI's sequence similarity search tool • supports analysis of DNA and protein databases • 80,000 searches per day

  19. OMIM is… • Online Mendelian Inheritance in Man • catalog of human genes and genetic disorders • edited by Dr. Victor McKusick, others at JHU

  20. Books is… • searchable resource of on-line books

  21. TaxBrowser is… • browser for the major divisions of living organisms • (archaea, bacteria, eukaryota, viruses) • taxonomy information such as genetic codes • molecular data on extinct organisms

  22. Structure site includes… • Molecular Modelling Database (MMDB) • biopolymer structures obtained from • the Protein Data Bank (PDB) • Cn3D (a 3D-structure viewer) • vector alignment search tool (VAST)

  23. Review ofGenetics, Biochemistry& Evolution

  24. Human Genome Project

  25. What is a typical Genomic structure for a Eukaryotic gene?

  26. Synonymous vs. nonsynonymous changes

  27. Synonymous Substitution Non-synonymous Substitution

  28. Central Dogma • DNA  RNA  protein • sequence  structure  function  evolution

  29. What kind of modifications Are made to Eukaryotic mRNAs?

  30. RNA Modifications

  31. What are cDNAs?

  32. Protein structures • X-ray crystallography and Nuclear magnetic resonance (NMR) • Primary structure • linear AA • Secondary structure- • alpha helix and beta sheet • Tertiary structures- • 3-d that exposes binding domains etc

  33. Linkage maps • YAC Yeast artificial chromosome & • BAC Bacterial artificial chromosome -used to clone large pieces of DNA -overlapping clones • Are genes linked?

  34. Organization of genomes • Groups of genes within a species -Comparative Genomics • plastid genomes and mt genomes

  35. How do we determine functions of genes?

  36. How do we determine functions of genes? • Expression patterns • Northerns • RT-PCR • SAGE • Microarrays • Transgenics • insert genes what results? • Mutants • classical genetics • molecular genetics • And Functional Protein Assays

  37. Charles Darwin • Descent with modification • species change through time and are related to a common ancestor • Natural Selection is the process by which this change occurs

  38. Understanding Natural selection • acts on individuals though consequences occur in populations • Individual’s phenotype reason survived and reproduced • after a time this will change the distribution in the population, • what ultimately changes? • Gene pool

  39. New alleles • Point change is all that is needed • not always a "big deal" • neutral change • can be in Sickle cell anemia

  40. Gene duplication • creates an additional copy of a gene • unequal cross-over • X-rays • Are these duplicates maintained in populations? • Psuedogenes

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