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The Gene Ontologies

The Gene Ontologies (GO) is a system that classifies biological knowledge into categories such as Biological Process, Molecular Function, and Cellular Component. It provides a common language for annotating gene products from any species, allowing for comparison of information across organisms.

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The Gene Ontologies

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  1. The Gene Ontologies A Common Language for Annotation of Genes from Yeast, Flies and Mice …and Plants and Worms …and Humans …and anything else!

  2. Gene Ontology Objectives • GO represents concepts used to classify specific parts of our biological knowledge: • Biological Process • Molecular Function • Cellular Component • GO develops a common language applicable to any organism • GO terms can be used to annotate gene products from any species, allowing comparison of information across species

  3. Expansion of Sequence Info

  4. Entering the Genome Sequencing Era Eukaryotic Genome SequencesYear Genome # Genes Size (Mb) Yeast (S. cerevisiae) 1996 12 6,000 Worm (C. elegans) 1998 97 19,100 Fly (D. melanogaster) 2000 120 13,600 Plant (A. thaliana) 2001 125 25,500 Human (H. sapiens, 1st Draft) 2001 ~3000 ~35,000

  5. Baldauf et al. (2000) Science290:972

  6. Comparison of sequences from 4 organisms MCM3 MCM2 CDC46/MCM5 CDC47/MCM7 CDC54/MCM4 MCM6 These proteins form a hexamer in the species that have been examined

  7. http://www.geneontology.org/

  8. Outline of Topics • Introduction to the Gene Ontologies (GO) • Annotations to GO terms • GO Tools • Applications of GO

  9. What is an Ontology? (from OED) 1721 BAILEY, Ontology, an Account of being in the Abstract. 1733 (title) A Brief Scheme of Ontology or the Science of Being in General. a1832 BENTHAMFragm. Ontol. Wks. 1843 VIII. 195 The field of ontology, or as it may otherwise be termed, the field of supremely abstract entities, is a yet untrodden labyrinth. 1884 BOSANQUET tr. Lotze's Metaph. 22 Ontology..as a doctrine of the being and relations of all reality, had precedence given to it over Cosmology and Psychology, the two branches of enquiry which follow the reality into its opposite distinctive forms.

  10. Sriniga Srinivasan, Chief Ontologist, Yahoo! The ontology. Dividing human knowledge into a clean set of categories is a lot like trying to figure out where to find that suspenseful black comedy at your corner video store. Questions inevitably come up, like are Movies part of Art or Entertainment? (Yahoo! lists them under the latter.) -Wired Magazine, May 1996

  11. The 3 Gene Ontologies • Molecular Function = elemental activity/task • the tasks performed by individual gene products; examples are carbohydrate binding and ATPase activity • Biological Process = biological goal or objective • broad biological goals, such as mitosis or purine metabolism, that are accomplished by ordered assemblies of molecular functions • Cellular Component= location or complex • subcellular structures, locations, and macromolecular complexes; examples include nucleus, telomere, and RNA polymerase II holoenzyme

  12. Example: Gene Product = hammer Function (what) Process (why) Drive nail (into wood) Carpentry Drive stake (into soil) Gardening Smash roach Pest Control Clown’sjuggling object Entertainment

  13. Biological Examples Biological Process Molecular Function Biological Process Molecular Function Cellular Component Cellular Component

  14. Terms, Definitions, IDs term: MAPKKK cascade (mating sensu Saccharomyces) goid: GO:0007244 definition: OBSOLETE. MAPKKK cascade involved in transduction of mating pheromone signal, as described in Saccharomyces. definition_reference: PMID:9561267 comment: This term was made obsolete because it is a gene product specific term. To update annotations, use the biological process term 'signal transduction during conjugation with cellular fusion ; GO:0000750'. definition: MAPKKK cascade involved in transduction of mating pheromone signal, as described in Saccharomyces

  15. Directed Cyclic Graph Figure 4.1. Life cycles of heterothallic and homothallic strains of S. cerevisiae. Heterothallic strains can be stably maintained as diploids and haploids, whereas homothallic strains are stable only as diploids, because the transient haploid cells switch their mating type, and mate. An Introduction to the Genetics and Molecular Biology of the Yeast Saccharomyces cerevisiae Fred Sherman 2000; Modified from: F. Sherman, Yeast genetics. The Encyclopedia of Molecular Biology and Molecular Medicine, pp. 302-325, Vol. 6. Edited by R. A. Meyers, VCH Pub., Weinheim, Germany,1997.

  16. Parent-Child Relationships Nucleus Nuclear envelope Nucleoplasm Nucleolus Chromosome Perinuclear space A child is a subset of a parent’s elements The cell component term Nucleus has 5 children

  17. “Tree” Relationships Derivation of Romance languages from Latin. From R.A. Hall Jr., Introductory Linguistics; originally published by Chilton Books, now distributed by Rand McNally & Co.

  18. Ontology Relationships Directed Acyclic Graph http://www.ebi.ac.uk/ego

  19. Evidence Codes for GO Annotations http://www.geneontology.org/doc/GO.evidence.html

  20. IEAInferredfromElectronicAnnotation ISSInferred from Sequence Similarity IEPInferred from Expression Pattern IMPInferred from Mutant Phenotype IGIInferred from Genetic Interaction IPIInferred from Physical Interaction IDAInferred from Direct Assay RCA Inferred from Reviewed Computational Analysis TASTraceable Author Statement NASNon-traceable Author Statement ICInferred by Curator NDNo biological Data available

  21. IEAInferred from Electronic Annotation • Sequence Similarity (BLAST) • Automatic transfer from mappings (InterPro2GO, EC2GO etc.) • -> Not manually reviewed

  22. ISSInferred from Sequence or Structural Similarity • Sequence similarity • Recognized domains • Structural similarity -> Use of ‘with’ column recommended

  23. IEPInferred from Expression Pattern • Transcript levels (Northerns, microarrays) • Protein levels (Western blots) -> Timing or localization of expression -> Biological process annotations

  24. IMPInferred from Mutant Phenotype • Gene mutation/knockout • Overexpression/ectopic expression • Anti-sense experiments • RNAi experiments • Specific protein inhibitors

  25. IGIInferred from Genetic Interaction • Suppressors, synthetic lethals… • Functional complementation • Rescue experiments • -> Use of ‘with’ column recommended

  26. IPIInferred from Physical Interaction • 2-hybrid interactions • Co-purification • Co-immunoprecipitation • Ion/complex/protein binding experiments • -> Use of ‘with’ column recommended

  27. IDAInferred from Direct Assay • Enzyme assays • In vitro reconstitution (e.g. transcription) • Immunofluorescence (for cell. comp.) • Cell fractionation (for cell. comp.) • Physical interaction/binding assay

  28. RCAInferred from Reviewed Computational Analysis • Non-sequence-based computational methods • Genome-wide analyses (e.g. 2-hybrid) • Combinations of large-scale experiments

  29. TASTraceable Author Statement • Support from review article • Textbook ‘common knowledge’ • -> Data that can be ‘traced’ back

  30. NASNon-traceable Author Statement • Database entries that don't cite a paper • -> Data that cannot be ‘traced’ back

  31. ICInferred by Curator • Not supported by any direct evidence • Inferred from other GO annotations • -> GO term in ‘with/from’ column required

  32. NDNo biological Data available Curator found no information supporting any annotation • molecular function unknown GO:0005554 • biological process unknown GO:0000004 • cellular component unknown GO:0008372

  33. Term Hierarchy TAS/IDA IMP/IGI/IPI ISS/IEP NAS IEA

  34. Qualifiers The qualifier modifies the interpretation of a GO term NOT: explicit note that a gene product is not associated with a GO term colocalizes_with: only transient localization, or low resolution of an assay contributes_to: gene product that is part of a complex can be annotated to the process/function of the complex http://www.geneontology.org/GO.annotation.shtml#qual

  35. http://www.geneontology.org/doc/GO.evidence.html

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