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 a candidate OBO-Foundry ontology for in vivo cell types Generalized, species-neutral cell types Initially developed by Jonathan Bard, Seung Rhee, and Michael Ashburner 1 Project funded to support the Gene Ontology 1 Bard 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 Masci AM, 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 image from www.drmihm.com Diehl AD, et al J Biomed Inform. 2011 Meehan et al, BMC Bioinformatics. 2011

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

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

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’s H. 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 Plant ontology Cell line ontology (CLO) Ontology of Biomedical Investigations (OBI) “pruned” away plant cell types

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 Jyl Boline 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 OBO FormatOWL RDF/XML Standardhttp://purl.obolibrary.org/obo/ cl.obo http://purl.obolibrary.org/obo/c l.owl Basichttp://purl.obolibrary.org/obo/ cl-basic.obo http://purl.obolibrary.org/obo/c l-basic.owl Standard form = CL plus MIREOTed terms from other ontologies Basic form = CL with MIREOTed classes and references removed All forms of ontologies are pre-reasoned