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GO : the Gene Ontology “because you know sometimes words have two meanings”

GO : the Gene Ontology “because you know sometimes words have two meanings”. Amelia Ireland GO Curator EBI, Cambridge, UK. What’s in a name?. What is a cell?. Cell. Cell. Cell. Cell. Cell. Cell. Image from http://microscopy.fsu.edu. Cell. A cell can be a part or a whole organism.

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GO : the Gene Ontology “because you know sometimes words have two meanings”

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  1. GO : the Gene Ontology“because you know sometimeswords have two meanings” Amelia Ireland GO Curator EBI, Cambridge, UK

  2. What’s in a name? • What is a cell?

  3. Cell

  4. Cell

  5. Cell

  6. Cell

  7. Cell

  8. Cell Image from http://microscopy.fsu.edu

  9. Cell • A cell can be a part or a whole organism Images from http://microscopy.fsu.edu

  10. What’s in a name?

  11. What’s in a name? • Glucose synthesis • Glucose biosynthesis • Glucose formation • Glucose anabolism • Gluconeogenesis • All refer to the process of making glucose from simpler components

  12. What’s in a name? The problem: • Same name for different concepts • Different names for the same concept • Vast amounts of biological data from different sources  Cross-species or cross-database comparison is difficult

  13. What is the Gene Ontology? • A (part of the) solution: • The Gene Ontology: “a controlled vocabulary that can be applied to all organisms even as knowledge of gene and protein roles in cells is accumulating and changing” • A controlled vocabulary to describe gene products - proteins and RNA - in any organism.

  14. What is GO? • One of the Open Biological Ontologies • Standard, species-neutral way of representing biology • Three structured networks of defined terms to describe gene product attributes • More like a phrase book than a biology text book

  15. How does GO work? • What does the gene product do? • Where and when does it act? • Why does it perform these activities? What information might we want to capture about a gene product?

  16. No GO Areas • GO covers ‘normal’ functions and processes • No pathological processes • No experimental conditions • NO evolutionary relationships • NO gene products • NOT a system of nomenclature

  17. Cellular Component • where a gene product acts

  18. Cellular Component

  19. Cellular Component

  20. Cellular Component • Enzyme complexes in the component ontology refer to places, not activities.

  21. glucose-6-phosphate isomerase activity Molecular Function • activities or “jobs” of a gene product

  22. Molecular Function insulin binding insulin receptor activity

  23. Molecular Function drug transporter activity

  24. Molecular Function • A gene product may have several functions; a function term refers to a single reaction or activity, not a gene product. • Sets of functions make up a biological process.

  25. cell division Biological Process a commonly recognized series of events

  26. Biological Process transcription

  27. Biological Process regulation of gluconeogenesis

  28. Biological Process limb development

  29. Biological Process courtship behavior

  30. Anatomy of a GO term id: GO:0006094 name: gluconeogenesis namespace: process def: The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol. [http://cancerweb.ncl.ac.uk/omd/index.html] exact_synonym: glucose biosynthesis xref_analog: MetaCyc:GLUCONEO-PWY is_a: GO:0006006 is_a: GO:0006092 unique GO ID term name ontology definition synonym database ref parentage

  31. Anatomy of a GO term • Species-specific terms use the phrase “sensu xxx” - ‘in the sense of’ • stalk formation • sensu Plantae: slender or elongated structure that supports a plant, plant part or plant organ • sensu Dictyostelium: a tubular structure that consists of cellulose-covered cells stacked on top of each other and surrounded by an acellular stalk tube composed of cellulose and glycoprotein.

  32. Anatomy of a GO term • GO synonyms include alternative wordings, spellings, and related concepts • Broader, narrower, exact or related • Useful search aid name: glucose transport exact_synonym: gluco-hexose transport narrow_synonym: glucose shuttling

  33. Ontology Structure • Ontologies are structured as a hierarchical directed acyclic graph • Terms can have more than one parent and zero, one or more children • Terms are linked by two relationships • is-a  • part-of 

  34. Ontology Structure cell membrane chloroplast mitochondrial chloroplast membrane membrane is-a part-of

  35. True Path Rule • The path from a child term all the way up to its top-level parent(s) must always be true cell • nucleus • chromosome But what about bacteria?

  36. True Path Rule Resolved component ontology structure: cell • cytoplasm • chromosome • nuclear chromosome • nucleus • nuclear chromosome

  37. GO for it! • GO to http://www.ebi.ac.uk/~aji/intro.html

  38. GO Annotation • Using GO terms to represent the activities and localizations of a gene product • Annotations contributed by members of the GO Consortium • model organism databases • cross-species databases, eg. UniProt • Annotations freely available from GO website

  39. GO Annotation • Database object • gene or gene product • GO term ID • e.g. GO:0003677 • Reference for annotation • e.g. PubMed paper, BLAST results • Evidence code • from evidence code ontology

  40. GO Annotation • Electronic annotation • from mappings files • e.g. UniProt keyword2go • High quantity but low quality • Annotations to low level terms • Not checked by curators • Manual annotation • From literature curation • Time consuming but high quality

  41. GO Annotation ISS Inferred from Sequence/Structural Similarity IDA Inferred from Direct Assay IPI Inferred from Physical Interaction TAS Traceable Author Statement NAS Non-traceable Author Statement IMP Inferred from Mutant Phenotype IGI Inferred from Genetic Interaction IEP Inferred from Expression Pattern IC Inferred by Curator ND No Data available IEA Inferred from electronic annotation

  42. GO Annotate In this study, we report the isolation and molecular characterization of the B. napus PERK1 cDNA, that is predicted to encode a novel receptor-like kinase. We have shown that like other plant RLKs, the kinase domain of PERK1 has serine/threonine kinase activity. In addition, the location of a PERK1-GTP fusion protein to the plasma membrane supports the prediction that PERK1 is an integral membrane protein…these kinases have been implicated in early stages of wound response… Function: protein serine/threonine kinase activity ; GO:0004674 (IDA) Component: integral to plasma membrane ; GO:0005887 (IDA) Process: response to wounding ; GO:0009611 (NAS)

  43. GO for it (again)! • GO to http://www.ebi.ac.uk/~aji/annotI.html

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