RGD: A comparative genomics platform
© Henry Stewart Publications 2011
Received: 10 August 2010
Accepted: 10 August 2010
Published: 1 January 2011
The Rat Genome Database (RGD) (http://rgd.mcw.edu) provides a comprehensive platform for comparative genomics and genetics research. RGD houses gene, QTL and polymorphic marker data for rat, mouse and human and provides easy access to data through sophisticated searches, disease portals, interactive pathway diagrams and rat and human genome browsers.
The Rat Genome Database (RGD) (http://rgd.mcw.edu) is recognised as the premier resource for genetic, genomic and phenotype data for the laboratory rat, Rattus norvegicus. Since 1999, RGD has provided a comprehensive catalogue of genes, quantitative trait loci (QTL) and strains, along with software tools to retrieve and display data of interest to investigators using this organism. The disease focus of these researchers often results in the use of multiple model organisms, in addition to clinical studies, in their efforts to elucidate the mechanisms and underlying genetic factors involved in human disease. To meet the needs of such users, RGD focuses its manual curation efforts on the functional, phenotype and pathway data related to specific disease areas and has integrated human and mouse data to create a comprehensive platform for comparative genomics and genetics. Several of these components are highlighted here.
Major data elements in RGD. RGD houses data for rat, human and mouse genes and quantitative trait loci (QTL), rat and human polymorphic markers and rat strains. This table gives the number of each data element for each species contained in the RGD database
Numbers of genes, quantitative trait loci (QTL) and strains in disease portals. Each disease portal has a large number of manually curated rat, mouse and human genes, rat and human QTL and rat strains which have been experimentally shown to be related to the disease category covered by the portal
Cancer portal (breast, prostate, urogenital)
Cardiovascular disease portal
Neurological disease portal
Obesity/metabolic syndrome portal
Phenotype and models portal
GViewer provides users with a genome-wide view of rat genes and QTL retrieved from ontology-based searches. Single-term or Boolean searches across one or more ontologies allow for flexibility and ease of use for those unfamiliar with the ontologies. From the full genome view, users can zoom into a region to see additional details, and can add genes and QTL not retrieved with the initial search. The list of data objects in the display can easily be viewed, or exported for use in other applications. In addition, the GViewer provides links to the rat GBrowse (genome browser) for a closer view of genomic details.
Separate GBrowse applications for rat and human facilitate comparative analyses. The rat GBrowse includes a wealth of genomic data, including: gene models from RGD, the National Center for Biotechnology Information (NCBI) and Ensembl; genomic features such as QTLs, transfer RNAs, expressed sequence tags, and microRNAs; and SNPs from both NCBI's SNP database (dbSNP) and Ensembl. Additional information about each piece of data can be viewed as pop-up 'balloons' by mousing over the display. These balloons also include access to more complete information via links to records at RGD and other databases. Many of these features and data types are also available in RGD's human GBrowse, including human genes and QTLs. The Ensembl SNP track on the human GBrowse gives users the ability to browse through known polymorphisms in their genomic region of interest.
Rat, mouse and human synteny can be displayed in both the rat and human GBrowse tools. Regions of synteny are shown as individual species-specific 'synteny blocks'. Orthologous genes are highlighted by shaded connections between genes in the three species. This makes evolutionary alterations such as differences in gene size and spacing, or areas of sequence inversion, easy to spot.
Navigating between the rat and human genome browsers is simplified by the inclusion of a link from the pop-up balloon for each human orthologue or human synteny block on the rat GBrowse to the same gene or synteny block in the human browser, and vice versa. Users interested in finding QTLs in corresponding regions in the two species, for instance, can use this feature to compare the human QTLs in the regions syntenic to a rat QTL of interest, or rat QTLs in the regions syntenic to a human QTL of interest, with ease. Synteny IDs such as 'ratMatch.1023' and 'humanMatch.1023' group the syntenic regions in all three species and are the same in both the rat and human browsers to aid this type of navigation.
To find polymorphic markers between two or more rat strains, RGD's SNPlotyper tool is ideal. The tool includes SNPs from the STAR SNP consortium, dbSNP, funcSTAR, the CASCAD database and the Wellcome Trust Rat SNP resources. Users choose a region of the genome and strains from a list of 200 included in the tool. SNPlotyper returns both an exportable list of SNPs and their genotypes in each strain, and a haplotype diagram showing alternative alleles as different coloured blocks. This allows users to distinguish polymorphic SNPs and strain-specific haplotype blocks at a glance.
When looking for information on how these SNPs relate to genes or QTLs, researchers can use RatMine, a tool based on the InterMine technology developed by the FlyMine and ModENCODE teams at the Cambridge Systems Biology Centre . RatMine integrates data for genes, QTLs, proteins, SNPs and strains, as well as ontology annotations for these data types. Researchers can build their own queries to extract data of interest, or utilise prebuilt template queries for answers to commonly used questions. Once a query is run, it returns a list of genomic elements that can be saved and used for analyses within RatMine or exported for use in other applications. Lists of genes or proteins, whether derived from a RatMine query or uploaded by the researcher, are viewed on the 'list analysis' page. This provides information about objects in the list, as well as a variety of 'widgets' which automatically perform enrichment analyses for ontology annotations such as disease and pathway, chromosomal locations and publications associated with that group of genes or proteins.
The RGD provides a unique comparative genomics platform for researchers interested in comprehensive rat, mouse and human data. Unique datasets include human QTL, signalling and regulatory pathways and detailed disease data catalogues. In addition, multiple genome tools allow the user to zoom across chromosomes, as well as zoom in to specific gene models, while providing syntenic views of data for easier comparisons. These make RGD an outstanding resource, not only for rat researchers, but also for those using mouse or conducting human studies.
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