OBO Foundry Workshop 2009 Cell Ontology (CL) Preliminary review

Cell Ontology (CL) 19. Versioning – format-version: 1.2 – date: 09:12: :05 – auto-generated-by: OBO-Edit beta51 – default-namespace: cell – remark: $Revision: 1.38 $ Drafted by Jonathan Bard, Michael Ashburner, David States, Seung Y. Rhee, and Pascal Gaudet. Incorporating terms and synonyms from the eVOC cell ontology of Janet Kelso, Win Hide et al. Hematopoietic cell terms revised by Alexander Diehl, MGI, The Jackson Laboratory. Contact Oliver Hofmann, at SANBI, University of the Western Cape.

General CL Attributes 1. Clearly defined domain - naturally-occurring and experimentally-derived cell types from all of the biological kingdoms – eukaryotic, prokaryotic and plant. (Not cell lines) 2. Relevant to biomedical research – yes 3. OBO Foundry principles being followed - for the most part, yes. 13. Openly available – yes. 14. Syntactical correctness - available in.obo format. 18. Uniqueness of all identifiers and preferred terms - terms and identifiers appear to be unique in the OBO Foundry space.

CL Modularity & Interoperability 4. Modular – yes. 5. Interoperation with other ontologies – Not well documented (general problem for OBO ontologies), but yes. Use of CL by other ontologies – The Gene Ontology (GO) is actively using the CL as a source for the re- definition of GO terms as cross-products (~25%-30% of GO annotations are associated with a CL term). – ZFIN and the Infectious Disease Ontology (IDO) are using CL for cross- product term generation. – Gautheret group (William Ritchie) at the Université Paris-Sud used CL to derive a Cell-line ontology. – The Plant Ontology (CSHL) and eVOC (SANBI) appear to be users as well ( Use of other ontologies by CL – The CL is attempting to utilize other OBO Foundry ontologies as appropriate. For example, the CL has begun to use terms from the Protein Ontology in its cell type definition.

Domain Coverage 6.Adequate coverage of defined domain - A wide variety of cell type terms are included. The hematopoietic branch appears to be especially well developed. The domain appears to be well covered.

Outreach 8. Collaborative development through the engagement of relevant domain stakeholders and developers of neighboring ontologies - The development of the CL appears to be in transition. Although this needs to be verified, it appears that the CL development coordinator is transitioning from Oliver Hoffman to Alexander Diehl. As part of this transition, Dr. Diehl has actively engaged the immunology research community to flesh out the hematopoietic cell branch. The end result has been a major improvement in both the content and the structure of this branch. Similar outreach to other relevant communities is encouraged. 9. Tracker for submissions of new terms and errors - yes, through Sourceforge. 10. Help desk and responsiveness - there are 52 requests that remain open at the Sourceforge site. This may reflect the recent transition in development leadership and inadequate funding, but remains a concern none-the-less.

Use 22. Degree to which the ontology is being used in data annotation - this is difficult to assess at the moment (general problem for OBO ontologies). – On one hand, Mouse Genome Informatics has been using the CL in conjunction with the GO for around 5 years, and the GO Consortium is promoting the use of the CL in GO annotation by other MODs. According to Melissa Haendel (Univ. Oregon), 5892 expression and 3384 phenotype annotations use CL terms in the ZFIN database. 32 literature references mention the CL either formally by citation or informally in text. – On the other hand, some resources have been waiting with great anticipation for certain parts of the ontology to be fleshed out. For example, the Immunology Database and Analysis Portal ( is planning on linking the hematopoietic branch of the CL to the output of analytical algorithms being used to identify cell populations in high-dimensional flow cytometry data.

Structure 12. Classification principles stated – no (general problem for OBO ontologies). 21. RO relations used - entire ontology based on is_a and derives_from relations. In general, the relations are properly applied, with some exceptions (see 23 below). 7. Inference support in structure - the ontology does support inferencing based on its structure, but suffers from the challenge of multiple inheritance (see 23 below). 23. Multiple and inconsistent inheritance - in some case, cell branches are defined based on function (e.g. barrier cell), in other cases based on their anatomic location (e.g. circulating cell), and in other cases based on their embryonic origin (e.g. ectodermal cells). This inevitably leads to multiple inheritance.

Multiple & Inconsistent Inheritance

Metadata & Definitions 11. Ontology metadata – some metadata items found on the Sourceforge tracker; the Cell Ontology has a wiki page ( although it has not been heavily used Clarity and precision of definitions - some definitions are missing. The definitions that are found are often derived from relevant reference publications, but many of the current definitions need to be improved. Some of the definitions in the hematopoietic branch are Aristotelian, which has helped in the accuracy of the hierarchy in this branch. 20. Completeness of ontology term metadata - ~30% of terms lack definitions. No other metadata is included.

CL Summary Domain is well delineated and coverage is relatively complete; ontology is open and available in common syntax General problems of incomplete metadata, statement of classification principles and lack of direct funding support. Specific problem of multiple and inconsistent inheritance, lack of term metadata and lack of ongoing curation

Definitions