Rat Genome Database

RGD
Content
Description The Rat Genome Database
Organisms Rattus norvegicus (rat)
Contact
Research center Medical College of Wisconsin
Laboratory Human Molecular and Genetics Center
Authors Mary E. Shimoyama, PhD; Howard J. Jacob, PhD
Primary citation PMID 25355511
Access
Website rgd.mcw.edu
Download URL RGD Data Release

The Rat Genome Database (RGD) is the premiere location for rat genomics, genetics, physiology and functional data, as well as data for comparative genomics between rat, human and mouse.[1] RGD is responsible for attaching biological information to the rat genome via structured vocabulary, or ontology, annotations assigned to genes and quantitative trait loci (QTL), and for consolidating rat strain data and making it available to the research community. RGD is working with groups such as the Programs for Genomic Applications[2] at MCW and the National BioResource Project for the Rat (NBPR-Rat) in Japan[3] to collect and make available comprehensive physiologic data for a variety of rat strains. They are also developing a suite of tools for mining and analyzing genomic, physiologic and functional data for the rat, and comparative data for rat, mouse and human.

RGD began as a collaborative effort between leading research institutions involved in rat genetic and genomic research. Its goal, as stated in RFA: HL-99-013, was the establishment of a Rat Genome Database to collect, consolidate, and integrate data generated from ongoing rat genetic and genomic research efforts and make these data widely available to the scientific community. A secondary, but critical goal was to provide curation of mapped positions for quantitative trait loci, known mutations and other phenotypic data.

The rat continues to be extensively used by researchers as a model organism for investigating pharmacology, toxicology, general physiology and the biology and pathophysiology of disease.[4] In recent years, there has been a rapid increase in rat genetic and genomic data. In addition to this, the Rat Genome Database has become a central point for information on the rat for research and now features information on not just genetics and genomics, but physiology and molecular biology as well. There are tools and data pages available for all of these fields that are curated by RGD staff.[5]

Data

RGD's Data page[6] lists eight types of data stored in the database: Genes, QTLs, Markers, Maps, Strains, Ontologies, Sequences and References. Of these, six are actively used and regularly updated. The RGD "Maps" datatype refers to legacy genetic and radiation hybrid maps. This data has been largely supplanted by the rat whole genome sequence. The "Sequences" data type is not a full list of either genomic, transcript or protein sequences, but rather mostly contains PCR primer sequences which define simple sequence length polymorphism (SSLP) and expressed sequence tag (EST) Markers. Such sequences are useful primarily for researchers still using these markers for genotyping their animals and for distinguishing between markers of the same name. The six major data types in RGD are as follows:

Genome Tools

RGD's Genome tools[10] include both software tools developed at RGD and tools from third party sources.

Genome tools developed at RGD

RGD develops web-based tools designed to use the data stored in the RGD database for analyses in rat and across species. These include:

Third party genome tools adapted for use with RGD data

RGD offers several "third party" software tools that have been adapted for use on the website utilizing data stored in the RGD database. These include:

Additional Data and Tools in RGD

Phenotypes and Models Portal

RGD's Phenotypes and Models portal[17] focuses on strains, phenotypes and the rat as a model organism for physiology and disease. The Phenotypes and Models portal has five sections: "Phenotypes", "Strains & Models", "Meet Joe Rat", "PhenoMiner" and "Strain Medical Records".

Diseases

As of July 2015, RGD had nine disease portals[20]

[21]

Disease portals consolidate the data in RGD for a specific disease category and present it in a single group of pages. Genes, QTLs and strains annotated to any disease in the category are listed, with genome-wide views of their locations in rat, human and mouse (see "Genome Viewer" in Genome tools developed at RGD). Additional sections of the portal display data for phenotypes, biological processes and pathways related to the disease category. Pages are also supplied to give users access to information about rat strains used as models for one or more diseases in the category, tools that could be used to analyze the data and additional resources related to the disease category.

Pathways

RGD's Pathway resources[22][23] include an ontology[24] of pathway terms (encompassing not only metabolic pathways but also disease, drug, regulatory and signaling pathways), as well as interactive diagrams of the components and interactions of selected pathways; "Pathway Suites and Suite Networks", i.e. groupings of related pathways which all contribute to a larger process such as glucose homeostasis or gene expression regulation; and Physiological Pathway diagrams which display networks of organs, tissues, cells and molecular pathways at the whole animal or systems level.

Knockouts

Until recently, direct, specific genomic manipulations in the rat were not possible. However, with the rise of technologies such as Zinc finger nuclease- and CRISPR -based mutagenesis techniques, that is no longer the case.[25] Groups producing rat gene knockouts and other types of genetically modified rats include the Human and Molecular Genetics Center at MCW. RGD links to information about the rat strains produced in these studies via pages about the PhysGen Knockout project[26] and the MCW Gene Editing Rat Resource Center (GERRC),[27] accessed from RGD page headers. Funding for both the PhysGenKO project and the GERRC came from the National Heart Lung and Blood Institute (NHLBI). The stated goal of both projects was to produce rats with alterations in one or more specific genes related to the mission of the NHLBI. Genes were nominated by rat researchers. Nominations were adjudicated by an External Advisory Board. In the case of the PhysGenKO project, many of the rats produced by the group were phenotyped using a standardized high-throughput phenotyping protocol and the data is available in RGD's PhenoMiner tool.

RGD Community Outreach and Education

RGD reaches out to the rat research community in a variety of ways including an email forum, a news page, a Facebook page, and regular attendance and presentations at scientific meetings and conferences.[28] Additional educational activities include the production of tutorial videos, both outlining how to use RGD tools and data, and on more general topics such as biomedical ontologies and biological (i.e. gene, QTL and strain) nomenclature. These videos are hosted on a number of online video hosting sites including YouTube.

Funding

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute (NHLBI) on behalf of the NIH. The grant includes some additional funding from the National Human Genome Research Institute (NHGRI). As of July 2015, the principal investigator of the grant was Mary E. Shimoyama, PhD who took over this leadership position from Howard J. Jacob, PhD in early 2015.[29]

Accession numbers and Genome Assembly

As of July 2015, the most current genomic sequence for rat is available under accession numbers AABR07000001-AABR07073554 in the international sequence databases (GenBank, DDBJ and EMBL). The most current assembly is Rnor_6.0. The assembly level is "chromosome" and the genome representation is "full", including a sequence of the Y chromosome (missing from all previous assemblies).[30]

References and External Links

  1. Shimoyama M, De Pons J, Hayman GT, et al. (2015). "The Rat Genome Database 2015: genomic, phenotypic and environmental variations and disease". Nucleic Acids Res. 43 (Database issue): D743–50. doi:10.1093/nar/gku1026. PMC 4383884. PMID 25355511.
  2. PGA. "PhysGen Programs for Genomic Applications". Pga.mcw.edu. Retrieved 2015-07-15.
  3. NBRP-Rat. "The National BioResource Project for the Rat in Japan". anim.med.kyoto-u.ac.jp. Retrieved 2015-07-15.
  4. Aitman TJ, Critser JK, Cuppen E, et al. (2008). "Progress and prospects in rat genetics: a community view". Nat. Genet. 40 (5): 516–22. doi:10.1038/ng.147. PMID 18443588.
  5. RGD. "About RGD - Rat Genome Database". Rgd.mcw.edu. Retrieved 2013-02-17.
  6. "RGD Data - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-08.
  7. 1 2 Laulederkind SJ, Shimoyama M, Hayman GT, et al. (2011). "The Rat Genome Database curation tool suite: a set of optimized software tools enabling efficient acquisition, organization, and presentation of biological data". Database (Oxford) 2011: bar002. doi:10.1093/database/bar002. PMC 3041158. PMID 21321022.
  8. 1 2 Shimoyama M, Hayman GT, Laulederkind SJ, et al. (2009). "The rat genome database curators: who, what, where, why". PLoS Comput. Biol. 5 (11): e1000582. doi:10.1371/journal.pcbi.1000582. PMC 2775909. PMID 19956751.
  9. RGD. "About RGD Ontologies - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-08.
  10. RGD. "Genome Tools - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-08.
  11. Wikimedia. "Overgo (genetics)". wiktionary.org. Retrieved 2015-07-13.
  12. de la Cruz N, Bromberg S, Pasko D, et al. (2005). "The Rat Genome Database (RGD): developments towards a phenome database". Nucleic Acids Res. 33 (Database issue): D485–91. doi:10.1093/nar/gki050. PMC 540004. PMID 15608243.
  13. Stein LD, Mungall C, Shu S, et al. (2002). "The generic genome browser: a building block for a model organism system database". Genome Res. 12 (10): 1599–610. doi:10.1101/gr.403602. PMC 187535. PMID 12368253.
  14. Skinner ME, Uzilov AV, Stein LD, Mungall CJ, Holmes IH (2009). "JBrowse: a next-generation genome browser". Genome Res. 19 (9): 1630–8. doi:10.1101/gr.094607.109. PMC 2752129. PMID 19570905.
  15. Smith RN, Aleksic J, Butano D, et al. (2012). "InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data". Bioinformatics 28 (23): 3163–5. doi:10.1093/bioinformatics/bts577. PMC 3516146. PMID 23023984.
  16. Rachel L, Julie S, Daniela B, et al. (2015). "Cross-organism analysis using InterMine". Genesis. doi:10.1002/dvg.22869. PMID 26097192.
  17. RGD. "Phenotypes & Models - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  18. RGD. "Phenotype Data - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-14.
  19. Laulederkind SJ, Liu W, Smith JR, et al. (2013). "PhenoMiner: quantitative phenotype curation at the rat genome database". Database (Oxford) 2013: bat015. doi:10.1093/database/bat015. PMC 3630803. PMID 23603846.
  20. RGD. "RGD Disease Portals - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  21. Twigger SN, Shimoyama M, Bromberg S, Kwitek AE, Jacob HJ (2007). "The Rat Genome Database, update 2007--easing the path from disease to data and back again". Nucleic Acids Res. 35 (Database issue): D658–62. doi:10.1093/nar/gkl988. PMC 1761441. PMID 17151068.
  22. Petri V, Shimoyama M, Hayman GT, et al. (2011). "The Rat Genome Database pathway portal". Database (Oxford) 2011: bar010. doi:10.1093/database/bar010. PMC 3072770. PMID 21478484.
  23. Hayman GT, Jayaraman P, Petri V, et al. (2013). "The updated RGD Pathway Portal utilizes increased curation efficiency and provides expanded pathway information". Hum. Genomics 7: 4. doi:10.1186/1479-7364-7-4. PMC 3598722. PMID 23379628.
  24. Petri V, Jayaraman P, Tutaj M, et al. (2014). "The pathway ontology - updates and applications". J Biomed Semantics 5 (1): 7. doi:10.1186/2041-1480-5-7. PMC 3922094. PMID 24499703.
  25. Flister MJ, Prokop JW, Lazar J, Shimoyama M, Dwinell M, Geurts A (2015). "2015 Guidelines for Establishing Genetically Modified Rat Models for Cardiovascular Research". J Cardiovasc Transl Res 8 (4): 269–77. doi:10.1007/s12265-015-9626-4. PMID 25920443.
  26. RGD. "PhysGen Knockouts - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  27. RGD. "Gene Editing Rat Resource Center". Rgd.mcw.edu. Retrieved 2015-07-21.
  28. RGD. "Rat Community - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  29. NIH. "Project Information for grant HL64541: Rat Genome Database". nih.gov. Retrieved 2015-07-15.
  30. NIH. "Rnor_6.0 - Assembly - NCBI". nih.gov. Retrieved 2015-07-15.
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