Reflecting the above considerations, we have taken a two-stage approach to further development of the hematopoietic cells in the Cell Ontology. In the first stage, which is now complete, we revised current terms and added new terms so that all hematopoietic cell type terms now have textual definitions that contain all the necessary details to define the cells logically. These terms have been directly incorporated into the existing ontology. Fig. 2A shows a typical OBO term stanza for one of these new terms, “induced T-regulatory cell.”
We have also separated the hematopoietic terms from the complex hierarchy of the original CL as much as possible, so that the section of the ontology containing these terms represents a true is_a hierarchy. Fig. 1B shows the simplified hierarchy for the cell type “macrophage.” In restructuring the ontology for the hematopoietic cells, we have eliminated the multiple inheritance via the artifactual high-level terms such as “cell by histology.” “cell by nuclear number,” or “cell by function.” Instead, information about cellular qualities is captured in the textual definitions where it is relevant, and is being used to build logical definitions for the cell types in the second stage of the work, as described below.
The version of the CL incorporating the changes in the hematopoietic terms accomplished in this first stage of revision has been given the working name “CL1.5”. (Note this does not refer to the CVS revision number within the cell.obo file itself, but rather the data-version tag.) Within CL1.5 there are many concrete improvements to CL content in the area of hematopoietic cells. We have created many new terms for individual cell types, including over 40 terms for T-lineage cells, over 40 terms for B-lineage cells, several natural killer cell terms, over 30 terms for monocytes and macrophages, and over 30 terms for dendritic cells. Other new terms have been introduced for various hematopoietic progenitor cell types. As discussed above, most of these new terms have been defined by structural criteria (protein expression) sometimes in conjunction with functional or anatomical relationships. An exception to this general rule is that most of the new macrophage terms are defined based on their anatomical location with protein expression criteria added where supported by the literature. All these new and revised terms are present in the publicly available version of the CL (www.obofoundry.org/cgi-bin/detail.cgi?id=cell). We have provided references within the ontology to published articles or textbooks that were used in developing the individual definitions for the majority of hematopoietic terms. For the rest, the term references are to the curators who developed the definitions based on their expert knowledge. All terms in the CL that were revised or developed during the NIAID workshop and its follow-up work have also been given the reference ID GO_REF:0000031, which refers to a brief description of the workshop in a list of references maintained at the GO Consortium web site (www.geneontology.org).
The ontology structure has been improved in important areas such as T cell and B cell development. Lineage relationships via the develops_from relation are now provided for many additional cell types. In general the hematopoietic terms are presented as species neutral, but species-specific information is incorporated in some definitions where necessary and comments have been added to provide clarity to data annotators, especially in cases where certain cell types have no close homologue in another species.
The second stage of development will be the extension of the hematopoietic term definitions into full cross-products as discussed above. The revised definitions provided in the first step will enable this extension in a fairly efficient manner depending upon the availability of the necessary terms in external ontologies. The initial step in this direction was taken by Masci and colleagues, who developed an ontology for dendritic cell types DC–CL, which is based on cross-product principles and is the foundation of the revised dendritic cell terms in CL1.5 [10]. DC–CL terms for types of dendritic cells are based on structural criteria (surface protein expression) with a few cell types also defined by relationships to functions or dispositions. DC–CL utilizes an expanded range of relation types based on those in the OBO Relation Type Ontology (www.obofoundry.org/cgi-bin/detail.cgi?id=relationship) in order to be more expressive about the cellular location and degree of protein expression (e.g. has_plasma_membrane_part, has_high_membrane_amount). We intend to use these relations together with the definitions provided by Masci et al. to provide logical definitions for the hematopoietic terms.
Recently, the Gene Ontology Consortium obtained an ARRA Competitive Revision grant to allow the cross-product/logical definition approach to be extended to the whole of the CL to create version “CL2.0.” As a first step we are developing the hematopoietic terms of CL1.5 into an external mini-ontology, “Hemo-CL,” based on these cross-products. A provisional version of Hemo-CL is available at obo.cvs.sourceforge.net/viewvc/obo/obo/ontology/anatomy/cell_type/hemo_CL.obo. Fig. 2B shows the OBO term stanza for term “induced T-regulatory cell” as it is represented in Hemo-CL. This is illustrated graphically in Fig. 2C. We are working with the curators of the Protein Ontology to ensure that the 600+ protein terms needed for Hemo-CL are found in the Protein Ontology. Completion of the Hemo-CL subontology is expected in 2010.
Reflecting the above considerations, we have taken a two-stage approach to further development of the hematopoietic cells in the Cell Ontology. In the first stage, which is now complete, we revised current terms and added new terms so that all hematopoietic cell type terms now have textual definitions that contain all the necessary details to define the cells logically. These terms have been directly incorporated into the existing ontology. Fig. 2A shows a typical OBO term stanza for one of these new terms, “induced T-regulatory cell.”
We have also separated the hematopoietic terms from the complex hierarchy of the original CL as much as possible, so that the section of the ontology containing these terms represents a true is_a hierarchy. Fig. 1B shows the simplified hierarchy for the cell type “macrophage.” In restructuring the ontology for the hematopoietic cells, we have eliminated the multiple inheritance via the artifactual high-level terms such as “cell by histology.” “cell by nuclear number,” or “cell by function.” Instead, information about cellular qualities is captured in the textual definitions where it is relevant, and is being used to build logical definitions for the cell types in the second stage of the work, as described below.
The version of the CL incorporating the changes in the hematopoietic terms accomplished in this first stage of revision has been given the working name “CL1.5”. (Note this does not refer to the CVS revision number within the cell.obo file itself, but rather the data-version tag.) Within CL1.5 there are many concrete improvements to CL content in the area of hematopoietic cells. We have created many new terms for individual cell types, including over 40 terms for T-lineage cells, over 40 terms for B-lineage cells, several natural killer cell terms, over 30 terms for monocytes and macrophages, and over 30 terms for dendritic cells. Other new terms have been introduced for various hematopoietic progenitor cell types. As discussed above, most of these new terms have been defined by structural criteria (protein expression) sometimes in conjunction with functional or anatomical relationships. An exception to this general rule is that most of the new macrophage terms are defined based on their anatomical location with protein expression criteria added where supported by the literature. All these new and revised terms are present in the publicly available version of the CL (www.obofoundry.org/cgi-bin/detail.cgi?id=cell). We have provided references within the ontology to published articles or textbooks that were used in developing the individual definitions for the majority of hematopoietic terms. For the rest, the term references are to the curators who developed the definitions based on their expert knowledge. All terms in the CL that were revised or developed during the NIAID workshop and its follow-up work have also been given the reference ID GO_REF:0000031, which refers to a brief description of the workshop in a list of references maintained at the GO Consortium web site (www.geneontology.org).
The ontology structure has been improved in important areas such as T cell and B cell development. Lineage relationships via the develops_from relation are now provided for many additional cell types. In general the hematopoietic terms are presented as species neutral, but species-specific information is incorporated in some definitions where necessary and comments have been added to provide clarity to data annotators, especially in cases where certain cell types have no close homologue in another species.
The second stage of development will be the extension of the hematopoietic term definitions into full cross-products as discussed above. The revised definitions provided in the first step will enable this extension in a fairly efficient manner depending upon the availability of the necessary terms in external ontologies. The initial step in this direction was taken by Masci and colleagues, who developed an ontology for dendritic cell types DC–CL, which is based on cross-product principles and is the foundation of the revised dendritic cell terms in CL1.5 [10]. DC–CL terms for types of dendritic cells are based on structural criteria (surface protein expression) with a few cell types also defined by relationships to functions or dispositions. DC–CL utilizes an expanded range of relation types based on those in the OBO Relation Type Ontology (www.obofoundry.org/cgi-bin/detail.cgi?id=relationship) in order to be more expressive about the cellular location and degree of protein expression (e.g. has_plasma_membrane_part, has_high_membrane_amount). We intend to use these relations together with the definitions provided by Masci et al. to provide logical definitions for the hematopoietic terms.
Recently, the Gene Ontology Consortium obtained an ARRA Competitive Revision grant to allow the cross-product/logical definition approach to be extended to the whole of the CL to create version “CL2.0.” As a first step we are developing the hematopoietic terms of CL1.5 into an external mini-ontology, “Hemo-CL,” based on these cross-products. A provisional version of Hemo-CL is available at obo.cvs.sourceforge.net/viewvc/obo/obo/ontology/anatomy/cell_type/hemo_CL.obo. Fig. 2B shows the OBO term stanza for term “induced T-regulatory cell” as it is represented in Hemo-CL. This is illustrated graphically in Fig. 2C. We are working with the curators of the Protein Ontology to ensure that the 600+ protein terms needed for Hemo-CL are found in the Protein Ontology. Completion of the Hemo-CL subontology is expected in 2010.
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