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A genomics-based systems approach towards drug repositioning for rheumatoid arthritis

机译:基于基因组学的类风湿关节炎药物重定位系统方法

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摘要

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of synovial joints. RA affects up to 1 % of the population worldwide. Currently, there are no drugs that can cure RA or achieve sustained remission. The unknown cause of the disease represents a significant challenge in the drug development. In this study, we address this challenge by proposing an alternative drug discovery approach that integrates and reasons over genetic interrelationships between RA and other genetic diseases as well as a large amount of higher-level drug treatment data.We first constructed a genetic disease network using disease genetics data from Genome-Wide Association Studies (GWAS). We developed a network-based ranking algorithm to prioritize diseases genetically-related to RA (RA-related diseases). We then developed a drug prioritization algorithm to reposition drugs from RA-related diseases to treat RA.
机译:背景类风湿关节炎(RA)是一种慢性自身免疫性疾病,其特征在于炎症和滑膜关节破坏。 RA影响全球多达1%的人口。当前,尚无可治愈RA或实现持续缓解的药物。疾病的未知原因代表了药物开发中的重大挑战。在这项研究中,我们通过提出一种替代药物发现方法来应对这一挑战,该方法整合了RA和其他遗传疾病之间的遗传相互关系以及大量高级药物治疗数据的原因,并提出了理由。来自全基因组关联研究(GWAS)的疾病遗传学数据。我们开发了一种基于网络的排名算法,以区分与RA遗传相关的疾病(RA相关疾病)的优先级。然后,我们开发了一种药物优先排序算法,以重新定位RA相关疾病中的药物以治疗RA。

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