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Revising the Cell Ontology

Revising the Cell Ontology. Terrence Meehan, Christopher Mungall , Alexander Diehl The Jackson Laboratory Lawrence Berkeley National Laboratory University at Buffalo School of Medicine and Biomedical Sciences. Background.

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Revising the Cell Ontology

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  1. Revising the Cell Ontology Terrence Meehan, Christopher Mungall, Alexander Diehl The Jackson Laboratory Lawrence Berkeley National Laboratory University at Buffalo School of Medicine and Biomedical Sciences

  2. Background • Cell ontology (CL) is acandidate OBO-Foundry ontology for in vivo cell types • Generalized, species-neutral cell types • Initially developed by Jonathan Bard, Seung Rhee, and Michael Ashburner1 • Project funded to support the Gene Ontology 1Bard et al. Genome Biology, 6:R21 (2005)

  3. Increasing the Utility of the CL • Integrate CL with other ontologies • Logical definitions (cross-products, intersections) • Supply different ontology formats (OBO,OWL) • Enhance content • Promote use to the biomedical research community

  4. Integrating- Ontologies Referenced An improved ontological representation of dendritic cells as a paradigm for all cell types MasciAM, BMC Bioinformatics 2009, 10:70

  5. Melanophage intersection_of: CL:0000864 ! tissue-resident macrophage intersection_of: has_part CHEBI:25179 ! melanin intersection_of: part_of UBERON:0002097 ! skin of body Diehl AD, et al J Biomed Inform. 2011 Meehan et al, BMC Bioinformatics. 2011 image from www.drmihm.com

  6. OBO Reasoner misses Inconsistencies • Contradictory axioms missed by OBO Edit Reasoner • Negation not possible in OBO Reasoners develops_from has_plasma_membrane_part lacks_plasma_membrane_part

  7. Short Cut relations • Expand the logic of OBO relationships • Use features of OWL reasoners • has_plasma_membrane_part • EquivalentTo: has_partsome (GO:’plasma membrane’ and has_part some ?Y) • lacks_plasma_membrane_part • - has_partexactly O (GO:’plasma membrane’ and has_part some ?Y)

  8. Build Process- CL = cell.obo

  9. Enhancing Content- cell types from the FMA • Foundation Model Anatomy (FMA)1 • Ontology of human anatomical structure • Use OBOL- • Parse cell types from ontology • attempt to automatically create logical definitions • succeeded with about 200 • manually added 500 1 A reference ontology for biomedical informatics: the Foundational Model of Anatomy. Rosse C, Mejino JL Jr. J Biomed Inform. 2003 Dec;36(6):478-500

  10. Enhancing Content- A “win-win” for both ontologies • Based metazoan cell types on FMA’sH. sapiens cell types • Improved the higher level structure of CL

  11. Enhancing Content- A “win-win” for both ontologies FMA CL

  12. Referencing the FMA ‘muscle cell’ (CL:0000187) has xref ‘muscle cell’ (FMA:67328) EquivalentTo CL:0000187 part_of some NCBITaxon:9606

  13. Enhancing Content- Making Room Ontology of Biomedical Investigations (OBI) Cell line ontology (CLO) “pruned” away plant cell types Plant ontology

  14. CL collaborating with other groups in the biomedical community • Ontology developers • International Neuroinformatics Coordinating Facility (INCF) • ImmPort • Functional Annotation Of the Mammalian Genomes (FANTOM5)

  15. CL-INCF collaboration Use CL to harmonize representation of cell types described in different nomenclatures Patrick Ray, Joseph Shea

  16. Dr. David Dougall Dr. Scheuermann Group UT Southwestern Medical School

  17. CL and FANTOM5 • Mapping transcriptional start sites using single molecule sequencer (Helicos) • Finding the transcriptional regulatory networks that define every human cell type

  18. Summary • We have improved the content and structure of the CL • Integrating with other OBO ontologies • Continue to reach out to a wider audience

  19. Revising the CL- Thanks! The Jackson Laboratory • Judith Blake • David Hill Lawrence Berkeley National Laboratory • Suzanna Lewis Univ. at Buffalo • Barry Smith • Alan Ruttenberg • Patrick Ray • Joseph Shea INCF • Janis Breeze • JylBoline UT-Southwestern • Richard Scheuermann • David Dougall • Lindsay Cowell Duke • Anna Maria Masci OHSU • Nicole Vasilevsky Developers of the following: • FMA • Gene Ontology • Flybase • UBERON • Cell-Line Ontology • Protein Ontology • Plant Ontology • Ontology of Biomedical Investigations • PATO • Zebrafish Anatomy Ontology • Phenoscape And the participants in our two workshops This work was supported by an NHGRI-funded, ARRA administrative supplement grant HG002273-09Z to the parent grant, HG002273, to the Gene Ontology Consortium and by the INCF

  20. Support Different Ontology versions • Standard form = CL plus MIREOTed terms from other ontologies • Basic form = CL with MIREOTedclasses and references removed • All forms of ontologies are pre-reasoned

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