Revising the Cell Ontology

Terrence Meehan, Christopher Mungall, Alexander Diehl

The Jackson LaboratoryLawrence Berkeley National LaboratoryUniversity at Buffalo School of Medicine and Biomedical Sciences

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 Ashburner1

•Project funded to support the Gene Ontology

1Bard et al. Genome Biology, 6:R21 (2005)

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

Integrating- Ontologies Referenced

An improved ontological representation of dendritic cells as a paradigm for all cell types Masci AM, BMC Bioinformatics 2009, 10:70

Melanophage

intersection_of: CL:0000864 ! tissue-resident macrophageintersection_of: has_part CHEBI:25179 ! melaninintersection_of: part_of UBERON:0002097 ! skin of body

image from www.drmihm.com

Diehl AD, et al J Biomed Inform. 2011Meehan et al, BMC Bioinformatics. 2011

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

Short Cut relations

has_plasma_membrane_partEquivalentTo: 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

Build Process- CL

= cell.obo

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

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

Enhancing Content- A “win-win” for both ontologies

FMA

CL

Referencing the FMA

‘muscle cell’ (CL:0000187) has xref‘muscle cell’ (FMA:67328)

EquivalentToCL:0000187 part_of some NCBITaxon:9606

Enhancing Content- Making Room

Plant ontology

Cell line ontology (CLO)

Ontology of Biomedical Investigations (OBI)

“pruned” away plant cell types

CL collaborating with other groups in the biomedical community

•Ontology developers•International Neuroinformatics

Coordinating Facility (INCF)•ImmPort•Functional Annotation Of the Mammalian

Genomes (FANTOM5)

CL-INCF collaboration

Use CL to harmonize representation of cell types described in different nomenclatures

Patrick Ray, Joseph Shea

Dr. David Dougall Dr. Scheuermann GroupUT Southwestern Medical School

CL and FANTOM5

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

Summary•We have improved the content and

structure of the CL

•Integrating with other OBO ontologies

•Continue to reach out to a wider audience

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 MasciOHSU• 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

Support Different Ontology versions

OBO Format OWL RDF/XML

Standard

http://purl.obolibrary.org/obo/cl.obo

http://purl.obolibrary.org/obo/cl.owl

Basic http://purl.obolibrary.org/obo/cl-basic.obo

http://purl.obolibrary.org/obo/cl-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