Data acquisition: the content provided in GPCR-OKB was extracted from articles published primarily during the past decade, and was recorded in the system in a format as close to the raw experimental data as possible to preserve objectivity. In cases where published evidence varied, the option ‘Evidence Varies’ highlighted the controversy. Thus, only original research papers were annotated; review articles were excluded. The latter, however, were checked to ensure that data from referenced original research articles were included in the GPCR-OKB.
: the GPCR-OKB web application was developed with the Grails web application framework, and supports both browsing and structured searches. Information is stored in XML files that follow the GPCR-OKB XML schema designed in agreement with the GPCR-OKB ontology (Skrabanek et al.
; see http://www.gpcr-okb.org
, The Ontology and Figure 1 in Supplementary Data
for a summary of the types of information captured, and the relationships between them). XML files are versioned with the Subversion version-control system, and can be downloaded directly (see FAQ for download instructions). The GPCR-OKB web application loads these XML files at startup, indexes text fields, and starts serving web pages. The system has been tested with a variety of modern web browsers and has no specific requirements (see FAQ for a list of recommended browsers).
For easy access to detailed information about individual subunits forming a GPCR oligomer, GPCR-OKB is linked to the latest release of the GPCRDB (Horn et al.
). Data are exchanged between GPCRDB and GPCR-OKB in XML format with an agreed-upon XML schema.
: information contained in GPCR-OKB can be browsed starting from any of the following titles: ‘Oligomers’, ‘Protomers’, ‘Methods’, ‘Phenotypic Changes’, ‘In Vivo
Evidence’, ‘Evidence for Physiological Relevance’ and/or ‘All Publications’. For simplicity, the GPCR-OKB only refers to GPCR oligomers, although the majority of published experimental studies cannot discriminate between dimers, tetramers or higher order oligomers. Oligomer names are derived from the names of their constituent protomers, separated by a hyphen, in alphabetic and numerical order, following the recommendations of Ferre et al.
), and with the organism in which they were characterized and the GPCR family name specified. When the same combination of protomers has been studied in different species, the GPCR-OKB lists these combinations as different entries. Tables of data offer an option to download information in a tab delimited format (see ‘Export to TSV’ button at the bottom of each table).
: the ‘Search’ tool at the top right side of each page (see Supplementary Figure 2
) provides keyword searches across different types of information. To search for a certain oligomer, the user specifies the name of the oligomer constituent protomers in the input box. Initially configured to search only ‘Oligomers’, the search tool also allows to search for protomers (only those that are part of stored oligomers), methods, or to restrict oligomer searches to specific types of oligomers. The latter are oligomers (i) with demonstrated phenotypic changes with respect to the constituent protomers (e.g. specific signaling or ligand binding cooperativity events), (ii) with published information about predicted interfaces of dimerization/oligomerization and (iii) with at least one or two of the following conditions satisfied: (a) evidence for physical association in native tissue or primary cells; (b) knowledge of specific functional properties in native tissue; and/or (c) information from knockout animals or RNAi technology. These conditions are NC-IUPHAR recommendations for recognition of a bona fide functional GPCR oligomer, according to a recent report (Pin et al.
: we are aware of at least two databases under development that provide information about GPCR oligomerization, i.e. the GRIP-DB system (Nemoto et al.
) and the gpDB relationship database (Theodoropoulou et al.
). These systems, however, are primarily focused on predicting or storing knowledge pertaining to protein–protein interactions between GPCR subtypes, GPCRs with partner G-proteins and/or GPCRs with effector molecules.