Rat Genome Database

Last updated
RGD
Content
DescriptionThe Rat Genome Database
Organisms Rattus norvegicus (rat)
Contact
Research center Medical College of Wisconsin & Biomedical Engineering
LaboratoryAnne E. Kwitek
AuthorsYsabel Chen & the RGD Team
Primary citation PMID   31713623
Access
Website rgd.mcw.edu
Download URL RGD Data Release

The Rat Genome Database (RGD) is a database of rat genomics, genetics, physiology and functional data, as well as data for comparative genomics between rat, human and mouse. [1] [2] 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. 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, human, and five other species.

Contents

RGD began as a collaborative effort between research institutions involved in rat genetic and genomic research. Its goal, as stated in the National Institutes of Health’s Request for Grant Application: HL-99-013, is the establishment of a Rat Genome Database to collect, consolidate, and integrate data generated from ongoing rat genetic and genomic research efforts and make this data widely available to the scientific community. A secondary, but critical goal is 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. [3] 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. [4]

Data

RGD’s data consists of manual annotations from RGD researchers as well as imported annotations from a variety of different sources. RGD also exports their own annotations to share with others.

RGD's Data page [5] 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 [9] 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

Phenotypes and Models Portal

RGD's Phenotypes and Models portal [13] focuses on strains, phenotypes and the rat as a model organism for physiology and disease.

Common NameScientific NameModel For
Chinchilla Chinchilla lanigera
  • The physiology, development, and function of the auditory system
  • The pathobiology of infections and development of vaccines
Thirteen-lined Ground Squirrel Ictidomys tridecemlineatus
  • Retinal function, metabolism, hypoxia/reperfusion, and longevity
Domestic Dog Canis lupus familiaris
  • Cancer, heart disease, autoimmune disorders, allergies, thyroid disease, cataracts, epilepsy, hip dysplasia, blindness, deafness, and more
Bonobo Pan paniscus
  • Cardiovascular disorders
Pig Sus scrofa
  • Renal function, vascular structure, obesity, cardiovascular disease, endocrinology, alcoholism, diabetes, nephropathy, and organ transplantation
Green Monkey Chlorocebus sabaeus
  • Neurodegeneration, diabetes and other metabolic syndromes
  • HIV transmission and AIDS
Naked Mole Rat Heterocephalus glaber
  • Biogerontology, aging and cancer resistance

Disease Portals

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. Further, access to the RGD's Multi-Ontology Enrichment Tool (MOET) is available at the bottom of the individual disease portals.

As of May 2021, RGD has fifteen disease portals: [16] [17]

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 [18] [19] include a Pathway Ontology [20] of pathway terms (developed and maintained at RGD, 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. Included on the diagram pages are a description, lists of pathway gene members and additional elements, tables of disease, pathway and phenotype annotations made to pathway member genes, associated references and an ontology path diagram. 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 are presented, as well as 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. [21] 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 [22] and the MCW Gene Editing Rat Resource Center (GERRC), [23] 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 is 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.

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, a Twitter account, and regular attendance and presentations at scientific meetings and conferences. [24] 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 can be viewed on several online video hosting sites including YouTube.

Funding

RGD is funded by grant R01HL64541 from the National Heart, Lung, and Blood Institute (NHLBI) on behalf of the National Institutes of Health (NIH). The principal investigator of the grant is Anne E. Kwitek, who was appointed to this leadership position from Mary E. Shimoyama, in March 2020. Melinda R Dwinell is Co-Investigator. [25]

New Genome Assembly

The new genome rat assembly, mRatBN7.2, was generated by the Darwin Tree of Life Project at the Wellcome Sanger Institute and has been accepted into the Genome Reference Consortium. mRatBN7.2 was derived from a male BN/NHsdMcwi rat that is a direct descendant of the female BN rat previously sequenced. The new BN rat reference genome was created using a variety of technologies including PacBio long reads, 10X linked reads, Bionano maps and Arima Hi-C. Its contiguity is similar to the human or mouse reference assemblies. It is available at NCBI’s GenBank and at RefSeq, and it will be made the primary assembly at RGD in the near future. [26]

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References

  1. ↑ Smith, Jennifer R.; Hayman, G. Thomas; Wang, Shur-Jen; Laulederkind, Stanley J. F.; Hoffman, Matthew J.; Kaldunski, Mary L.; Tutaj, Monika; Thota, Jyothi; Nalabolu, Harika S.; Ellanki, Santoshi L. R.; Tutaj, Marek A. (2020-01-08). "The Year of the Rat: The Rat Genome Database at 20: a multi-species knowledgebase and analysis platform". Nucleic Acids Research. 48 (D1): D731–D742. doi:10.1093/nar/gkz1041. ISSN   1362-4962. PMC   7145519 . PMID   31713623.
  2. ↑ 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.
  3. ↑ 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. S2CID   22522876.
  4. ↑ RGD. "About RGD - Rat Genome Database". Rgd.mcw.edu. Retrieved 2013-02-17.
  5. ↑ "RGD Data - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-08.
  6. 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.
  7. 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. Bibcode:2009PLSCB...5E0582S. doi: 10.1371/journal.pcbi.1000582 . PMC   2775909 . PMID   19956751.
  8. ↑ RGD. "About RGD Ontologies - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-08.
  9. ↑ RGD. "Genome Tools - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-08.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ Rachel L, Julie S, Daniela B, et al. (2015). "Cross-organism analysis using InterMine". Genesis. 53 (8): 547–60. doi:10.1002/dvg.22869. PMC   4545681 . PMID   26097192.
  13. ↑ RGD. "Phenotypes & Models - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  14. ↑ 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.
  15. ↑ RGD. "Phenotype Data - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-14.
  16. ↑ RGD. "RGD Disease Portals - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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 (1): 4. doi: 10.1186/1479-7364-7-4 . PMC   3598722 . PMID   23379628.
  20. ↑ 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.
  21. ↑ 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. PMC   4475456 . PMID   25920443.
  22. ↑ RGD. "PhysGen Knockouts - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  23. ↑ RGD. "Gene Editing Rat Resource Center". Rgd.mcw.edu. Retrieved 2015-07-21.
  24. ↑ RGD. "Rat Community - Rat Genome Database". Rgd.mcw.edu. Retrieved 2015-07-15.
  25. ↑ NIH. "Project Information for grant HL64541: Rat Genome Database". nih.gov. Retrieved 2015-07-15.
  26. ↑ NIH. "Rnor_6.0 - Assembly - NCBI". nih.gov. Retrieved 2015-07-15.
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