Cell Ontology Progress Report 2010

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STILL UNDER REVISION (12-10-10)

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
    • We have been prototyping the new CL structure using the hematopoeitic cell types as a test case.
    • Started month: 1
    • Estimated duration: 6 months
  • Add formal logical axioms to the CL.
    • We have made the first steps towards adding logical axioms to theCL. The first is the formal definition of the capable_of relation, required for linking cell types to biological processes (for example, Tr1 cells to IL-10 production). The LBL group has created the formal definition in terms of the Basic Formal Ontology (BFO) "disposition" class, and whilst the Jackson group has applied this in the prototype ontology.
    • Started month: 1
    • Estimated duration: 6 months
  • Add logical definitions using other OBO ontologies
    • 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.
    • Started month: 1
    • Estimated duration: 6 months
  • Implement automated reasoner strategy
    • Although we do not estimate commencing this until month 6 we have made some preliminary steps, partially implementing the MIREOT methodology within OBO-Edit. This allows the CL editors at Jackson to select classes from external ontologies and bring in only the subset of those ontologies that pertain to these referenced classes. This improves reasoner performance.
    • Estimated start month: 6
    • Estimated duration: 3 months
  • General software support
    • Support with managing ontology versions in Open Bio-Ontologies repository
    • OBO-Edit bug fixes
    • OBO-Edit tutorials for CL curators


Aim 2: Improving and extending the content of CL

  • We have begun planning for a Cell Ontology workshop, to be held May 18-19, 2009 at the Jackson Laborotory, Bar Harbor, Maine. The workshop will be used for discussion of general issues involved in the revision of the Cell Ontology.
  • We are implementing the cross-product/logical definition formulation of the hematopoietic terms. As part of this work, we are improving definitions for a number of cell types and adding new cell types.
  • We are working to add is_a parents to all terms in the CL.
  • We are preparing definitions for current nervous system terms in the CL that lack them.

Aim 3: Applying the CL to the GO

  • This work is to commence in month 6


Item 2 -- Percent Completion

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

LBL Portion

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 classes can 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 oboedit 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 (http://berkeleybop.org/~cjm/obo2owl/obo-syntax.html), which significantly extends on previous efforts made in 2007, before the OWL2 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.


[Return to 2010 Progress Reports]

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