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[在计算机模拟分析中检测与类风湿关节炎及其他自身免疫性疾病相关的共同通路]

[Detecting shared pathways linked to rheumatoid arthritis with other autoimmune diseases in a in silico analysis].

作者信息

Zheng W-Y, Zheng W-X, Hua L

机构信息

College of Biomedical Engineering, Capital Medical University, Beijing, 100069, PR China.

出版信息

Mol Biol (Mosk). 2016 May-Jun;50(3):530-9. doi: 10.7868/S0026898416030149.

Abstract

Pathway-based analysis approach has exploded in use during the last several years. It is successful in recognizing additional biological insight of disease and finding groupings of risk genes that represent disease developing processes. Therefore, shared pathways, with pleiotropic effects, are important for understanding similar pathogenesis and indicating the common genetic origin of certain diseases. Here, we present a pathway analysis to reveal the potential disease associations between RA and three potential RA-related autoimmune diseases: psoriasis, diabetes mellitus, type 1 (T1D) and systemic lupus erythematosus (SLE). First, a comprehensive knowledge mining of public databases is performed to discover risk genes associated with RA, T1D, SLE and psoriasis; then by enrichment test of these genes, disease-related risk pathways are detected to recognize the pathways common for RA and three other diseases. Finally, the underlying disease associations are evaluated with the association rules mining method. In total, we identify multiple RA risk pathways with significant pleiotropic effects, the most unsurprising of which are the immunology related pathways. Meanwhile for the first time we highlight the involvement of the viral myocarditis pathway related to cardiovascular disease (CVD) in autoimmune diseases such as RA, psoriasis, T1D and SLE. Further Association rule mining results validate the strong association between RA and T1D and RA and SLE. It is clear that pleiotropy is a common property of pathways associated with disease traits. We provide novel pathway associations among RA and three autoimmune diseases. These results ascertain that there are shared genetic risk profiles that predispose individuals to autoimmune diseases.

摘要

基于通路的分析方法在过去几年中得到了广泛应用。它成功地识别出了疾病的额外生物学见解,并发现了代表疾病发展过程的风险基因分组。因此,具有多效性的共享通路对于理解相似的发病机制和指明某些疾病的共同遗传起源非常重要。在此,我们进行了一项通路分析,以揭示类风湿性关节炎(RA)与三种潜在的RA相关自身免疫性疾病之间的潜在疾病关联:银屑病、1型糖尿病(T1D)和系统性红斑狼疮(SLE)。首先,对公共数据库进行全面的知识挖掘,以发现与RA、T1D、SLE和银屑病相关的风险基因;然后通过对这些基因的富集测试,检测与疾病相关的风险通路,以识别RA和其他三种疾病共有的通路。最后,使用关联规则挖掘方法评估潜在的疾病关联。我们总共识别出了多个具有显著多效性的RA风险通路,其中最不出人意料的是与免疫相关的通路。同时,我们首次强调了与心血管疾病(CVD)相关的病毒性心肌炎通路在RA、银屑病、T1D和SLE等自身免疫性疾病中的作用。进一步的关联规则挖掘结果验证了RA与T1D以及RA与SLE之间的强关联。显然,多效性是与疾病特征相关通路的共同特性。我们提供了RA与三种自身免疫性疾病之间新的通路关联。这些结果确定了存在使个体易患自身免疫性疾病的共享遗传风险特征。

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