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To Boldly GO…

Learn about the history of the Gene Ontology (GO), its current state, and its future directions. Explore the GO Consortium, its use in academia and industry, the criteria for the ontology, and its cross-products and term decomposition capabilities.

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To Boldly GO…

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  1. To Boldly GO… Amelia Ireland GO Curator EBI, Hinxton, UK

  2. A Brief History Of GO Past: • Began in 1998 as a collaboration between FlyBase, the Saccharomyces Genome Database (SGD) and the Mouse Genome Database (MGD) • About 3800 terms by 1999 • Ontology text files edited by hand (!)

  3. A Brief History Of GO Present: • GO Consortium includes 20+ genome databases • Used by many groups in academia and industry • Nearly 18000 terms • Four full time GO curators • Many tools and software • GO paradigm much imitated

  4. OBO • Web-based repository for open biological ontologies • Five criteria: • Open; no licensing or fees • Use common shared syntax • Orthogonal to existing OBO ontologies • Unique identifiers / namespace • Definitions for terms

  5. OBO http://obo.sf.net/

  6. Cross Products • Use GO in combination with other vocabularies to create more complex concepts Extension and Integration of the Gene Ontology:Combining GO vocabularies with external vocabularies. Hill DP, Blake JA, Richardson JE, Ringwald M. 2002. Genome Res12: 1982-1991

  7. Cross Products • GO has three ontologies • Biological process • Molecular function • Cellular component • Extend by combining with terms from other vocabularies

  8. chorismate mutase prephenate dehydratase chorismate _ prephenate _ phenylpyruvate H2O CO2 aromatic amino-acid transaminase glutamate oxoglutarate phenylalanine Cross Products • Narrative method: create terms manually as needed phenylalanine biosynthesis

  9. Cross Products • Combinatorial approach: create all combinations of terms (preferably using a script!) phenylalanine biosynthesis • biological process ontology • metabolism, biosynthesis, catabolism, regulation • biochemical ontology • chemicals involved in pathway

  10. Cross Products Demo

  11. Cross Products • Combinatorial method more thorough but may produce unwanted terms • Can also lead to massive term proliferation • Quality of terms (and definitions) depends on source ontologies • May be better to create cross products as a separate ontology or during annotation

  12. Term Decomposition • Parsing of GO terms • Work in progress; Chris Mungall, BDGP http://www.fruitfly.org/~cjm/obol-0.02/doc/obol-doc.html

  13. Term Decomposition • Many GO term names have a regular structure: [compound] binding [anatomical part] morphogenesis regulation of [process] x biosynthesis from y x biosynthesis, z pathway • These GO term strings follow consistent implicit naming rules

  14. Term Decomposition • Formal grammar: a rule system for parsing (decomposing) and generating (composing) sequences of symbols • Using an English language grammar, should be able to parse GO term strings into tokens and generate new GO term strings from these tokens • Definite Clause Grammar used as it can be augmented with additional logical constraints; implemented in Prolog

  15. Term Decomposition negative regulation of nucleotide biosynthesis negative regulation nucleotide biosynthesis modifies negative regulation of nucleotide biosynthesis negative regulation modifies negative regulation of nucleotide biosynthesis nucleotide biosynthesis modifies

  16. Term Decomposition

  17. Term Decomposition • Over 40% of GO terms can be (at least partially) decomposed • These can then be linked to terms from other OBO ontologies - anatomy, biochemistry, cell type, etc. • Missing GO terms and relationships suggested • Can also be used to suggest terms in other OBO ontologies

  18. Term Decomposition • Some standardization required • cytosolvscytosolic • Terms with multiple parses require biological knowledge • smooth muscle contraction vs smooth muscle contraction • Not all OBO ontologies complete • No protein / protein complex ontology

  19. Future GO • Strip out specific instances to leave general concepts in GO • eg. metabolism, differentiation, development • Develop a set of templates for creating composite terms from GO and other OBO ontologies for greater annotation accuracy and flexibility

  20. Future GO negative regulation of eye photoreceptor cell development negative regulation of eye photoreceptor cell development negative regulation of eye photoreceptor cell development negative regulation of eye photoreceptor cell development negative regulation of eye photoreceptor cell development • negative regulation from universal modifier ontology • eye from anatomy ontology • photoreceptor cell from cell type ontology • development from GO process ontology

  21. For more information… • GO • http://www.geneontology.org • OBO • http://obo.sf.net • Term decomposition / OBOL • http://www.fruitfly.org/~cjm/obol-0.02/doc/obol-doc.html

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