Department of Biomedical Engineering, The Rat Genome Database, Medical College of Wisconsin, Milwaukee, WI, USA.
Clinical and Translational Science Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
Mamm Genome. 2022 Mar;33(1):66-80. doi: 10.1007/s00335-021-09932-x. Epub 2021 Nov 5.
Model organism research is essential for discovering the mechanisms of human diseases by defining biologically meaningful gene to disease relationships. The Rat Genome Database (RGD, ( https://rgd.mcw.edu )) is a cross-species knowledgebase and the premier online resource for rat genetic and physiologic data. This rich resource is enhanced by the inclusion and integration of comparative data for human and mouse, as well as other human disease models including chinchilla, dog, bonobo, pig, 13-lined ground squirrel, green monkey, and naked mole-rat. Functional information has been added to records via the assignment of annotations based on sequence similarity to human, rat, and mouse genes. RGD has also imported well-supported cross-species data from external resources. To enable use of these data, RGD has developed a robust infrastructure of standardized ontologies, data formats, and disease- and species-centric portals, complemented with a suite of innovative tools for discovery and analysis. Using examples of single-gene and polygenic human diseases, we illustrate how data from multiple species can help to identify or confirm a gene as involved in a disease and to identify model organisms that can be studied to understand the pathophysiology of a gene or pathway. The ultimate aim of this report is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions.
模式生物研究通过定义具有生物学意义的基因与疾病关系,对于发现人类疾病的机制至关重要。大鼠基因组数据库(RGD,(https://rgd.mcw.edu))是一个跨物种知识库,是大鼠遗传和生理数据的首要在线资源。通过包含和整合人类和小鼠的比较数据以及其他人类疾病模型,如南美栗鼠、狗、倭黑猩猩、猪、13 条纹地松鼠、绿猴和裸鼹鼠,丰富了这一丰富的资源。通过将注释分配给基于与人类、大鼠和小鼠基因的序列相似性的记录,增加了功能信息。RGD 还从外部资源导入了经过充分支持的跨物种数据。为了能够使用这些数据,RGD 开发了一个强大的标准化本体、数据格式和疾病与物种为中心的门户基础设施,并辅以一套用于发现和分析的创新工具。通过单基因和多基因人类疾病的示例,我们说明了来自多个物种的数据如何帮助确定或确认基因是否与疾病有关,并确定可以研究的模型生物,以了解基因或途径的病理生理学。本报告的最终目的是不仅展示 RGD 作为大鼠研究社区核心资源的实用性,还展示其作为生物信息学工具的来源,以支持更广泛的受众,为寻找人类疾病的合适模型提供支持。