G-Protein Coupled Receptor Oligomerization Knowledge Base (GPCR-OKB) ontology project
G Protein-Coupled Receptors (GPCRs) are a large and diverse family of membrane proteins whose members participate in the regulation of most cellular and physiological processes and therefore represent key pharmacological targets. Although several bioinformatics resources support research on GPCRs, most of them have been designed based on the traditional assumption that monomeric GPCRs constitute the functional receptor unit (Figure 1 below). The increase in the frequency and number of reports about GPCR dimerization/oligomerization and the implication of oligomerization in receptor function makes necessary the ability to store and access information about GPCR dimers/oligomers electronically.
We present here the design blueprint for an information system that can manage the elements of information required to describe comprehensively the phenomena of both homo- and hetero-oligomerization of GPCRs. Specifically, we present the ontology (Figures 2-4 below) that we plan to use for the development of an intuitive and user-friendly GPCR-Oligomerization Knowledge Base (GPCR-OKB). This information system is being designed in close collaboration with experimental colleagues working on GPCR oligomerization, and adopts the list of recommendations recently stipulated by the NC-IUPHAR subcommittee for the recognition and nomenclature of GPCR multimers.
Our long term goal is to disseminate to the scientific community organized, curated, and detailed information about GPCR dimerization/oligomerization, and its related structural context.
Skrabanek L, Murcia M, Bouvier M, Devi L, George SR, Lohse MJ, Milligan G, Neubig R, Palczewski K, Parmentier M, Pin JP, Vriend G, Javitch JA, Campagne F, Filizola M. Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base. BMC Bioinformatics. 2007 May 30;8:177. PMID 17537266
The data in GPCR-OKB is manually curated. Guidelines on how to curate the data for entry into GPCR-OKB are provided here: Media:GPCR-OKB_Curator_Guidelines.pdf
The ontology files (developed in Protege) are below. To download them, use the 'Save as' option in your browser.
- OWL file: Media:GPCR-OKB_11.owl
- Protege project TAR file: Media:GPCR-OKB_11.tar
- Figure 1: Media:GPCRsignaling.tif Traditional and current views of GPCR signaling
- Figure 2: Media:GPCR-OKB11_oligomer.gif UML diagram of Oligomer concept and related classes
- Figure 3: Media:GPCR-OKB11_model.gif UML diagram of modeling-related concepts
- Figure 4: Media:GPCR-OKB11_phenotype.gif UML diagram of phenotype-related concepts
- Figure 5: Media:PhenotypicalChangeExamples11.jpg Examples of phenotypic changes represented in the ontology
Auto-generated documentation: http://phoebus.cs.man.ac.uk:9999/OWL/Presentation?url=http://pbtest.med.cornell.edu/wiki/uploads/1/1a/GPCR-OKB_11.owl
User Interface Mockup
We created a user interface prototype for the GPCR Oligomerization Knowledge Base (GPCR-OKB). The interface was static and contained no actual data. The prototype was meant to convey the breadth of information that would be stored in GPCR-OKB and to help optimize how the information will be presented in the finished system. This mockup has been discontinued now we have released the live application.
Files in the download section are updated as changes are made to the GPCR-OKB ontology. Filenames contain a version number. This number is incremented each time a more recent file is uploaded (unless the change is very minor). UML diagrams in the Figures section are updated concurrently with the OWL ontology.
The GPCR-OKB Web Application obtains its data via XML. The format of this XML is defined by a schema.
The GPCR-OKB Web Application exports Oligomer and Protein data to GPCR-DB via XML. The format of this XML is defined by a schema.
- Published first version of user interface mockup.
- We have included a new class in this ontology, called MeasuredBoolean, which has one field whose allowed values are 'true, false, not_measured'. This is now being used in many of the classes instead of Booleans. We have also added MeasuredVariation, whose values are 'increased, decreased, unchanged, not_tested'.
- To make the UML diagrams printable, have to save the PNG files from ArgoUML as GIFs via Photoshop, using 'Save for Web' and unchecking 'Transparency'.
- Included a tmTopology to the Protein class, with associated SecondaryStructureElement class.
- Shaded UML diagrams to make them more comprehensible.
- Removed MDSimulations concept; Analysis now relates to all simulations and post analysis of the structure.
- Subdivided MethodType into CreationMethod and IdentificationMethod.
- Removed Image concept.
- Cooperativity change to distinguish between changes in affinity and activity.
- Added a new Stoichiometry concept to store the stoichiometric relationship of GPCR proteins to their associated G-proteins.
- Changed subunit to monomer throughout.
- Added a boundMonomer attribute to LigandInducedEffect. The affectedSubunit attribute is now affectedMonomer, and is a Collection.
- Added a cellType attribute to IdentificationStudy, whose type is from the Cell Ontology.
- Removed the isHomodimer attribute from Oligomer.
- Added examples of IdentificationMethod and CreationMethod.
- Replaced all instances of "monomer" with "protomer".
- Removed attributes promotingLigands and inhibitingLigands from Oligomer, as well as isConstitutitvelyFormed.
- Created a new class call LigandEffectOnMeasurement which stores the effect that a ligand has on the measurement made by the method type (in the referring instance of IdentificationStudy).
- Added a comparedWith attribute to PhenotypicChange.
- Changed the name of the PharmacologicalProperty concept to LigandBinding.
- Changed the name of the SignalTransduction concept to Signaling.
- Changed Cooperativity to CrossTalk. Both Signaling and LigandBinding now can have instances of CrossTalk.
- Changed Trafficking to Internalization, removed the isExportedToMembrane attribute, and moved all attributes from LigandInducedEffect into the Internalization concept. Removed the LigandInducedConcept.
- Changed the affectedMonomer attribute in what was LigandInducedEffect (now in Internalization) to readoutProtomer.
- Moved the isDesensitized and isPhosphorylated attributes from what was LigandInducedEffect to Signaling.
- Removed the Stroichiometry concept and included its attributes in MechanismOfActivation.