© 2000 Oxford University Press
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Olfactory Receptor Database: a sensory chemoreceptor resource Emmanouil Skoufos1,2,*, Luis Marenco1, Prakash M. Nadkarni1, Perry L. Miller1 and Gordon M. Shepherd2 1Center
for Medical Informatics and 2Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06511, USA Received September 29, 1999; Revised and Accepted October 8, 1999
ABSTRACT The Olfactory Receptor Database (ORDB) is a WWWaccessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-proteincoupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has been constructed and is publicly available in a pilot mode. The database schema of ORDB has been changed from traditional relational to EAV/CR (EntityAttribute-Value with Classes and Relationships), which allows the interoperability of ORDB with other related databases as well as the creation of intradatabase associations among objects. This interoperability facilitates users to follow information from odor molecule binding to its putative receptor, to the properties of the neuron expressing the receptor, to a computational model of activity of olfactory bulb neurons. In addition, tools and resources have been added allowing users to access interactive phylogenetic trees and alignments of sensory chemoreceptors. ORDB is available via the WWW at http://ycmi.med.yale.edu/senselab/ordb/ INTRODUCTION The Olfactory Receptor Database (ORDB) (1) is a database containing properties and sequences of the olfactory receptorlike proteins (ORLs), vertebrate G-protein coupled receptors (GPCRs) that are thought to be the largest eukaryotic gene family, including ~1000 different genes in the mouse (2). In the olfactory epithelium, ORLs are thought to bind ~10 000 odor molecules. Until recently, however, there has been very little evidence about OR-ligand specificity (3–6). ORLs are expressed in 25 tissues in addition to olfactory epithelium, suggesting that members of this family of proteins may have functions beyond odor recognition (7). All ORLs, regardless of species
and tissue, share high sequence homology and have common sequence motifs that may be involved in similar signal transduction pathways (7). Putative olfactory receptors, which like the ORLs are GPCRs but have no sequence homology to the vertebrate ORLs, have been identified in Caenorhabditis elegans (8,9) and Drosophila (10,11). In addition, G-protein coupled pheromone receptors have been cloned from a variety of fungi (12), and vomeronasal G-protein coupled putative pheromone receptors have been identified in vertebrates (13,14). When ORDB was created in 1995, the original aim was to aid the cloning, sequencing and classification of the ORLs. The identification of the additional olfactory-related chemoreceptor gene families and the increasing interest in identifying specific ligand–receptor interactions resulted in the broadening of the scope of ORDB to include information about all GPCR sensory chemoreceptor proteins. ORDB is a member of the consortium of the GPCR databases that includes the GPCRDB (15), the GRAP mutant database (16), the mutation analysis of GPCRs database (17) and the GCRDb (18). ORDB contains entrylevel links with the other databases of the consortium when feasible. OVERVIEW OF THE DATABASE Version 4.0 of ORDB contains 812 sensory chemoreceptor entries from 27 species that represent the sequencing efforts of 77 laboratories worldwide. The different classes of GPCR sensory chemoreceptors in the database are: (i) olfactory receptor-like proteins (ORLs), (ii) C.elegans chemoreceptors (CCRs), (iii) vomeronasal receptors (VNRs), (iv) insect olfactory receptors (IORs), (v) fungal pheromone receptors (FPRs) and (vi) taste papilla receptors (TPRs). ORDB contains information about the tissue from which a receptor is cloned, the size (partial or full-length) of clones, chromosomal information, and direct links to the PubMed and/or GenBank records of the ORs. A recently introduced resource area contains original alignments and phylogenetic trees of all the receptor classes and certain tools that are coupled to the database, such as BLAST searching allowing all users to search for similarities between any sequence of their interest and all sequences in the database. OdorDB, a companion database that contains information about odor molecules (the ORL ligands) and their effects in various experimental settings has been released as a pilot beta version. ORDB is implemented using a database structure called EAV/CR (Entity-Attribute-Value with Classes and Relationships),
*To whom correspondence should be addressed. Tel: +1 203 785 3730; Fax: +1 203 785 6990; Email:
[email protected] Present address: Emmanouil Skoufos, 3rd Millennium Inc., 125 Cambridge Park Drive, Cambridge, MA 02140, USA
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Figure 1. ORDB receptor entry screen. A typical ORDB receptor screen is presented. Information includes ORDB sequential name (ORL464), OR type (ORL), organism (mouse), source tissue, chromosome, GenBank accession number, trivial name, source lab, sequencing lab, length of the clone, ligand information, nucleotide and amino acid sequence, type of clone and links to GenBank, PubMed and GPCRDB. Users can retrieve information about like receptors by using the ‘show others’ links or can retrieve information about particular values (e.g., mouse) in all linked databases through ‘bridge screens’ (Fig. 2) accessed by following the underlined link of the value of interest. Users can access any information in the database using the navigation frame on the left.
which has been developed to facilitate the implementation and integration of databases containing heterogeneous data (19). The basic EAV model has been used in a number of databases, including clinical databases, and involves the computer science principle of row modeling. EAV/CR extends the basic paradigm to allow complex data values (classes) and the explicit representation of relationships in the database (19). ORDB INTERFACE AND NAVIGATION ORDB implements frames to present an intuitive interface to the WWW user (Fig. 1). Users have several navigation choices from every page: they can search the database using keywords, search the sequences in the database using BLAST, browse the database records or go to the ORDB tools and resources page (Fig. 1). The flexible EAV/CR architecture of ORDB that is shared with OdorDB and NeuronDB (20), allows for interoperability of these related databases and for retrieval of related data from any of the databases. A receptor entry screen is presented in Figure 1. Users can access information on receptor parameters such as sequencing laboratory, data source, type of sequence, organism, tissue, size of OR clone, and be redirected to PubMed, GenBank and GPCRDB entries for the receptor, as in the previous version (Fig. 1). Furthermore, in this version users can retrieve information from OdorDB about odor molecule properties and from
NeuronDB about neuronal tissue properties. From the receptor entry screen (Fig. 1) users have the option of retrieving all receptor entries in ORDB with the same values in the field by following the ‘show other’ link. For example, in Figure 1, one can see all mouse receptors by following the ‘show other’ link at the ‘Organism’ level. The values themselves are links that direct the users to ‘bridge screens’ (Fig. 2) that contain information about the value in the field from the other related databases. For example, following the ‘olfactory receptor neuron’ link in Figure 1, the user will arrive at the bridge screen presented in Figure 2. This screen contains information about the olfactory receptor neuron in all three databases: the ‘Neuron’ link will direct the user to the NeuronDB entry of the olfactory receptor neuron properties, the ‘Experiments’ link will direct the user to a list of all experimental data in OdorDB that have olfactory receptor neuron as tissue and the ‘Olfactory Receptors’ link will direct the user to all receptors in ORDB that have been cloned from olfactory receptor neurons. Thus, users receive a multi-dimensional wealth of related information regarding a particular object. ORDB RESOURCES AND TOOLS AND FUTURE CONSIDERATIONS With the fourth version of ORDB we are introducing a ‘Resources and Tools’ area to organize the available tools and to provide several resources in response to many user requests.
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Figure 2. ORDB bridge screen. A typical ORDB bridge screen is presented. Through this screen users can retrieve related information about the olfactory receptor neuron in the linked databases: the ‘Neuron’ link will direct the user to the NeuronDB entry of the olfactory receptor neuron properties, the ‘Experiments’ link will direct the user to a list of all experimental data in OdorDB that have olfactory receptor neuron as tissue and the ‘Olfactory Receptors’ link will direct the user to a list of all receptors in ORDB that have olfactory receptor neuron as their source tissue.
The resources available include interactive originally produced alignments and phylogenetic trees of receptors, based on receptor class, which are free to users and which they are encouraged to use in their own research. In the tools and resources area we have included a gateway to BLAST searching (an additional gateway is available through the navigation frame, Fig. 1). Planned resources include: the classification of the ORLs according to the particular motifs present in their sequence (7); the automatic generation of a multi-level descriptor that includes species, ORDB ID (sequential name), laboratory (trivial) name, phylogenetic classification, chromosome information, tissue expressed, fulllength or partial clone and ligand information, which can act as a multi-level, database driven nomenclature of the ORLs; and the automatic generation of a sequential name upon receptor entry by a source laboratory. In the near future OdorDB will be populated with the experimental results of the >10 000 odor molecules. The internal flexibility of the EAV/CR schema, as well as the interoperability introduced between the databases will allow users to make virtual links between specific ORLs and their odor molecule ligands. ACKNOWLEDGEMENTS This work has been supported in part by NIH grant R01 DC02307 (Human Brain Project) and NIH grants G08 LM05583 and TI5 LM07056 from the National Library of Medicine.
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