Cell Ontology Progress Report 2010

Work on the Cell Ontology is funded by an ARRA Competitive Revision to the GO Consortium Grant. This work commenced on September 30, 2009. The project is based at MGI, with sub-contract work at LBNL.

Personnel

• Project Leaders
  • Alexander Diehl, The Jackson Laboratory/University at Buffalo (50% effort)
  • Christopher Mungall, LBNL (10% effort)

• Cell Ontology Curator
  • Terrence Meehan, The Jackson Laboratory (100% effort)

• Programmers
  • Amina Abdulla and Nomi Harris, LBNL (75% effort, split)

• Senior Advisors
  • Judith Blake, The Jackson Laboratory
  • Suzanna Lewis, LBNL

• External Consultants
  • Lindsay Cowell, Duke University
  • Anna Maria Masci, Duke University

Collaborations

• INCF Program on Ontologies for Neuroscience Task Force for Representation and Deployment, identification of nervous system cell types for addition to the CL.
• Ceri van Slyke, ZFIN, addition of fish cell types and other revisions to CL.
• Sirarat Sarntivijai and Oliver He, University of Michigan, development of the Cell Line Ontology.
• The Plant Ontology Consortium, plant cell types.
• David Osumi-Sutherland, Flybase, Drosophila cell types.
• Onard Mejino, Foundation Model of Anatomy, import of FMA cell types
• David Dougall and Richard Scheuermann, UT Southwestern, import of novel hematopoietic cell types identified via flow cytometry
• Helen Parkinson, EBI, assistance in making cell types in CL and the Experimental Factor Ontology compatible and in providing support for experimentally derived cell types in OBI.

Item 1 - Activities

Aim 1: Reforming the Structure of the Cell Ontology

• Devise new structure for the Cell Ontology
  • A new high level structure for the CL was approved at the May 2010 Cell Ontology Workshop. Parts have been implemented, and more will be in 2011.

• Add formal logical axioms to the CL.
  • A system of OWL macro expansions has been developed for CL relations such as "capable_of" that allow for easy conversion to OWL versions that can be more fully reasoned over using Protege reasoners.

• Add logical definitions using other OBO ontologies
  • Extensive computable definitions (AKA "logical definitions" or "cross-products") have been added to terms in the hematopoietic cell branch of the CL, and to some other terms in the CL.
  • We have identified the following ontologies as key to defining cell types:
    • PRO - Protein Ontology
    • GO - Gene Ontology (particularly biological processes such as immune response)
    • PATO - Phenotypic Quality Ontology
    • Uberon - We are also evaluating the use of a general-purpose gross anatomical ontology (Uberon) for certain cell types defined by location in the body.

• Implement automated reasoner strategy
  • This has been an integral part of our ongoing development of the CL.

• General software support
  • Support with managing ontology versions in Open Bio-Ontologies repository
  • OBO-Edit bug fixes

Aim 2: Improving and extending the content of CL

• We held a Cell Ontology workshop, on May 18-19, 2010 at the Jackson Laborotory, Bar Harbor, Maine, and extensively discussed both ontological and biological aspects of CL development.
• A workshop on neurons and nervous system cell types is scheduled for April 12-14, 2011. More information may be found here.
• We have implementing the computable defintion (AKA "logical definition" or "cross-product") formulation of the hematopoietic terms. As part of this work, we have improved definitions for a number of cell types and adding many new cell types.
• A paper, "Logical Development of the Cell Ontology" by Meehan, Masci, Abdulla, Cowell, Blake, Mungal, and Diehl, which described the work on the hematopoietic cells in the CL has been accepted (December 2010) for publication in BMC Biouinformatics.
• We have imported a large number of terms from the FMA into the CL.
• We have added is_a parents to all terms in the CL.
• We have prepared textual and logical definitions for current nervous system terms in the CL that lack them, although these are not yet implemented in cell.obo.
  
  

Aim 3: Applying the CL to the GO

• We are using manual and automated methods to ensure interoperability between the GO and CL for cell types and the logical relationships between them.

Item 2 -- Percent Completion

• Based on current progress towards completion of our aims we are on track, with 60% of the work accomplished.

LBL Contributions to CL development

ONTOLOGY ALIGNMENT AND INTEGRATION: we have supported the JAX ontology editors by providing and executing tools to integrate human cell types represented in the FMA (Foundational Model of Anatomy) into CL. These tools identified generic cell types in common between the two ontologies, and used the Obol toolkit (developed at Berkeley) to identify compositional class expressions for specific cell types (e.g. "smooth muscle cell of jejunum"). These compositional classescan then be integrated automatically, using the cross-species gross anatomy ontology UBERON.

ONTOLOGY EDITOR SUPPORT: we have provided ontology editor support to the JAX editors of the ontology, improving the OBO-Edit ontology editing environment in reponse to curator requests. We have also implemented a variant of the MIREOT (Minimal Information Retrieved for External Ontology Terms) strategy which allows scalable integration across multiple ontologies. We have also devised a build environment for the CL, which allows the easy distribution of multiple versions for different purposes, and uses OWL reasoners to classify and perform logical consistency analysis on the ontology automatically.

ONTOLOGY LANGUAGE SUPPORT: we identified key areas in which the ontology format used by the Gene Ontology was insufficient for representing cell types. Rather than move wholesale to the more expressive OWL (Ontology Web Langauge) formalism, which would have entailed abandoning tools and interoperation with model organism databases, we enhanced obo format using a macro mechanism and implemented a prototype macro expansion engine (http://precedings.nature.com/documents/5292/version/1). This allowed us to have the best of both worlds, and to be able to transition between the oboedit environment, and the Protege4 editors environment, and to use OWL reasoners to classify the ontology.

This work also necessitated creation of a formal specification of obo format and its translation to OWL ([1]), which significantly extends on previous efforts made in 2007, before theOWL2 language was finalized.

Related Publications for 2010

Diehl AD, Augustine AD, Blake JA, Cowell LG, Gold ES, Gondré-Lewis TA, Masci AM, Meehan TF, Morel PA, Nijnik A, Peters B, Pulendran B, Scheuermann RH, Yao QA, Zand MS, Mungall CJ. 2010. Hematopoietic Cell Types: Prototype for a Revised Cell Ontology. J Biomed Inform. doi:10.1016/j.jbi.2010.01.006.

Mungall CJ, Bada M, Berardini TZ, Deegan J, Ireland A, Harris MA, Hill DP, Lomax J. 2010. Cross-product extensions of the Gene Ontology. J Biomed Inform. doi:10.1016/j.jbi.2010.02.002.

Meehan TF, Masci AM, Abdulla A, Cowell LG, Blake JA, Mungall CJ, Diehl AD, 2010, Logical Development of the Cell Ontology, accepted for publication in BMC Bioinformatics.

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