Cell Ontology Workshop 2010 May 18-19, 2010 Highseas Conference Center The Jackson Laboratory...
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Transcript of Cell Ontology Workshop 2010 May 18-19, 2010 Highseas Conference Center The Jackson Laboratory...
Cell Ontology Workshop 2010
May 18-19, 2010
Highseas Conference Center
The Jackson Laboratory
Supported by
NHGRI HG002273-09Z
“an ARRA stimulus grant at work”
Workshop Attendees
Thanks to…
• The Jackson Laboratory• TJL Courses & Conferences – Laura Lelansky• Hurley Travel Experts – Beth Partridge
• The Gene Ontology Consortium – Judith Blake, Suzanna Lewis• The International Neuroinformatics Coordinating Facility• National Institute of Allergy and Infectious Diseases• National Human Genome Research Institute
Workshop Goals1) Review and discuss ongoing work on the Cell Ontology.
a. Work on hematopoietic cells
b. Work on nervous system cell types
c. Work to clean up other areas of the CL
2) Decide upon relations to employ and external ontologies to utilize in construction of logical definitions for cross-product terms.
Workshop Goals3) Decide upon how best to reform the high level structure of
the ontology.
4) Organize outreach efforts to import cell type terms from other ontologies and resources.
5) Discuss applications of the Cell Ontology.
6) Plan for the coming year of the grant and long-term support for the CL.
Overview of the Current Cell Ontology
• An ontology of cell types built by biologists for the needs of data annotation and analysis.
• The main branch organizes and enumerates in vivo cell types.
• The Cell Ontology is intended to cover cell types from all of biology.
Overview of the Current Cell Ontology
• An ontology of cell types built by biologists for the needs of data annotation and analysis.– How can we do this better?
• The main branch organizes and enumerates in vivo cell types.
• The Cell Ontology is intended to cover cell types from all of biology.
Overview of the Current Cell Ontology
• An ontology of cell types built by biologists for the needs of data annotation and analysis.– How can we do this better?
• The main branch organizes and enumerates in vivo cell types.– Is there an optimal organization to use?
• The Cell Ontology is intended to cover cell types from all of biology.
Overview of the Current Cell Ontology
• An ontology of cell types built by biologists for the needs of data annotation and analysis.– How can we do this better?
• The main branch organizes and enumerates in vivo cell types.– Is there an optimal organization to use?
• The Cell Ontology is intended to cover cell types from all of biology.– All cell types?– Should some cell types remain in organism-specific anatomy
ontologies and simply refer to more general CL types?
Overview of the Current Cell Ontology
• The Cell Ontology is not a list of specific cell lines, immortal or otherwise, although the Cell Ontology may be used to describe such cells if they correspond to an in vivo cell type.– Two cell line ontologies exist:
• CLKB Cell Line Ontology, (8743 cell lines)• MCCL Cell Line Ontology, (506 cell
lines)
• Nor is the Cell Ontology a list of in vitro methods for preparing cell cultures, although the Cell Ontology may be used to describe the resulting cells if they correspond to an in vivo cell type.
Overview of the Current Cell Ontology
• The Cell Ontology is not a list of specific cell lines, immortal or otherwise, although the Cell Ontology may be used to describe such cells if they correspond to an in vivo cell type.– Two cell line ontologies exist:
• CLKB Cell Line Ontology, http://clkb.ncibi.org/ (8743 cell lines)• MCCL Cell Line Ontology, http://www.molecularconnections.com/home/ontology
(506 cell lines)
– Also the Experimental Factor Ontology has over 530 cell lines.
• Nor is the Cell Ontology a list of in vitro methods for preparing cell cultures, although the Cell Ontology may be used to describe the resulting cells if they correspond to an in vivo cell type.
Overview of the Current Cell Ontology
• The Cell Ontology is not a list of specific cell lines, immortal or otherwise, although the Cell Ontology may be used to describe such cells if they correspond to an in vivo cell type.– Two cell line ontologies exist:
• CLKB Cell Line Ontology, http://clkb.ncibi.org/ (8743 cell lines)• MCCL Cell Line Ontology, http://www.molecularconnections.com/home/ontology
(506 cell lines)
– Also the Experimental Factor Ontology has over 530 cell lines.
• Nor is the Cell Ontology a list of in vitro methods for preparing cell cultures, although the Cell Ontology may be used to describe the resulting cells if they correspond to an in vivo cell type.– Presumably the Ontology for Biomedical Investigations should
provide terms for this type of information.
Overview of the Current Cell Ontology
• CL currently has 1030 cell type terms.
• Majority of terms are arranged in a multiple is_a hierarchy, with high-level categories denoting various cellular qualities.
• The exception is the hematopoietic cells which are arranged as a separate hierarchy with limited multiple inheritance.
• The representation of hematopoietic cells has been enhanced with extensive logical/computable definitions, but that work currently exists in a separate file.
• develops_from is the other major relationship used in the current CL.
Overview of the Current Cell Ontology
Overview of the Current Cell Ontology
Inferred Linksbased on
logical definitions
CL vs. OBO Foundry Principles (2006)
1. The ontology must be open… YES
2. The ontology must be in a shared common syntax… YES
3. The ontology has a unique identifier space… YES
4. The ontology provider has procedures for identifying distinct successive versions… YES
5. The ontology has a clearly specified and clearly delineated content… YES (for cell types in vivo, not for cell lines)
6. The ontologies include textual definitions for all terms… NO, but we are working towards this.
CL vs. OBO Foundry Principles (2006)
7. The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology… YES (more on this later)
8. The ontology is well documented… YES, but could be better.
9. The ontology has a plurality of independent users… YES
10.The ontology will be developed collaboratively with other OBO Foundry members… YES
CL vs. OBO Foundry Principles (2010)
• License: None stated as far as I know• Maintenance in light of scientific advance: Ongoing• Naming conventions: YES• Single Locus of Authority: YES following ARRA grant• Textual definitions (SOP) for all terms, plus equivalent
formal definitions (for at least a substantial number of terms): Ongoing
• All definitions of the genus-differentia form, utilizing (some) cross-products: Ongoing
CL vs. OBO Foundry Principles (2010)
• Single asserted is_a inheritance, with further is_a relations inferred: Ongoing, much work left to do.
• Terms in an ontology should correspond to instances in reality: Will come with restructuring.
• Orthogonality Issues: a few, such as the term “cell” – the term and definition of “cell” belong to CL. Presumably, all other ontologies, including GO CC, should reference the term “cell ; CL:0000000”.
ARRA Grant to Support the Cell Ontology
• An ARRA “stimulus” competitive revision to the main Gene Ontology Consortium grant was awarded to The Jackson Laboratory on September 30, 2009, with a 23 month term until August 31, 2011 for the purpose of revising and extending the Cell Ontology.
• Lawrence Berkeley National Laboratory holds a sub-contract under the grant.
ARRA Grant to Support the Cell Ontology
• Project Leaders
– Alexander Diehl, The Jackson Laboratory (50% effort)
– Christopher Mungall, LBNL (10% effort)
• Curator
– Terrence Meehan, The Jackson Laboratory (100% effort)
• Software Engineer
– Amina Abdulla, LBNL (50% effort)
• Supervising Principal Investigators
– Judith Blake, The Jackson Laboratory
– Suzanna Lewis, LBNL
Aims of the CL Grant
Aim 1: Reforming the structure of CL.• Improve the structure of the CL by providing logical
definitions based on relationships between individual CL terms and terms in external ontologies that provide information about particular qualities of a cell type.
• Use these logical definitions to classify and detect inconsistencies in the ontology.
Aims of the CL Grant
Aim 2: Improving and extending the content of CL.• Provide biologically-based textual definitions for all terms in
the CL in addition to logical definitions.• Work with specific groups of interested researchers on
improving the cell type terms in particular subfields of biology.
• Focus 1: Logical definitions for hematopoietic cells.• Focus 2: Enrich content for neurons.• Focus 3: Catalog developmental cell types and lineage in
order to facilitate stem cell research.
Aims of the CL Grant
• Aim 3: Applying the CL to the GO.• Ensure that all cell types referenced by the GO are in the
CL and that the ontological structure of GO terms that refer to cell types parallels the structure of the CL for those cell types.
• Build mechanisms in the GO annotation process to allow more expressive cell-based GO annotations that specify the cell type in which a gene product is active.
• Improve GO software tools to allow viewing, querying and analyses using cell-based search terms
Two Workshops under CL Grant
• Workshop 1, today and tomorrow– To address general aspects of Cell Ontology
development.
• Workshop 2, late 2010 or early 2011– To address nervous system cell types.– Will coordinate with INCF.– No location set.
Rough Timeline for CL grant
• Year 1 (to August 31, 2010)– Hematopoietic cell logical definitions.– Curate backlog of definitions and cell type requests.– Devise new high-level structure.– Begin restructuring of the rest of ontology with logical
definitions.– Workshop 1.
Rough Timeline for CL grant
• Year 2 (September 1, 2010 to August 31, 2011)– Continue restructuring of ontology with logical
definitions.– Focus on major improvements in the representation of
nervous system cell types.– Workshop 2.– Make improvements to AmiGO for display of CL-linked
GO annotations.
Overview of Grant Progress
• The hematopoietic cells are being restructured as cross-products with logical definitions. This work is about 90% complete, including the writing of a manuscript.
• So far minimal work has been done on most other cell types.– Currently 53 items remain open on CL SourceForge tracker.
(http://sourceforge.net/tracker/?group_id=76834&atid=925065)(thanks to Ceri Van Slyke for clearing some of these)
– Have collected list of another 30 or so cell types to add.– Have provided some definitions and proper is_a parents for a small
number of cell types.
Overview of Grant Progress
• Some groundwork for improving nervous system cell types done:– A set of definitions for nervous system cell types already in the CL
have been created – still need to move into main file.– Alex is representing the CL on the INCF Program on Ontologies for
Neural Structures Representation and Deployment Taskforce.
• Have set up an editors’ file for the CL, cell.edit.obo, and a system for publishing versioned changes to the main cell.obo file.
• Work on hematopoietic cell types has led to improvements to OBO-Edit for handling logical definitions.
Overview of Grant Progress
• Chris Mungall has developed a system for expanding shortcut relation types used in CL to RO-compliant expressions for incorporation into OBO-formatted files and which improves interoperability with OWL versions of the ontology.
• One publication, based on prior work:“Hematopoietic cell types: Prototype for a revised cell ontology.”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.
J Biomed Inform. 2010 Feb 1.PMID: 20123131