Ding Yanjun, Cui Mintian, Qian Jun, Wang Chao, Shen Qi, Ren Hongbiao, Li Liangshuang, Zhang Fengmin, Zhang Ruijie
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Department of Microbiology, WU Lien-Teh Institute, Harbin Medical University, Harbin, China.
Front Genet. 2021 Nov 11;12:758041. doi: 10.3389/fgene.2021.758041. eCollection 2021.
Autoimmune diseases (ADs) are a broad range of diseases in which the immune response to self-antigens causes damage or disorder of tissues, and the genetic susceptibility is regarded as the key etiology of ADs. Accumulating evidence has suggested that there are certain commonalities among different ADs. However, the theoretical research about similarity between ADs is still limited. In this work, we first computed the genetic similarity between 26 ADs based on three measurements: network similarity (NetSim), functional similarity (FunSim), and semantic similarity (SemSim), and systematically identified three significant pairs of similar ADs: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), myasthenia gravis (MG) and autoimmune thyroiditis (AIT), and autoimmune polyendocrinopathies (AP) and uveomeningoencephalitic syndrome (Vogt-Koyanagi-Harada syndrome, VKH). Then we investigated the gene ontology terms and pathways enriched by the three significant AD pairs through functional analysis. By the cluster analysis on the similarity matrix of 26 ADs, we embedded the three significant AD pairs in three different disease clusters respectively, and the ADs of each disease cluster might have high genetic similarity. We also detected the risk genes in common among the ADs which belonged to the same disease cluster. Overall, our findings will provide significant insight in the commonalities of different ADs in genetics, and contribute to the discovery of novel biomarkers and the development of new therapeutic methods for ADs.
自身免疫性疾病（ADs）是一大类疾病，其中针对自身抗原的免疫反应会导致组织损伤或功能紊乱，而遗传易感性被视为ADs的关键病因。越来越多的证据表明，不同的ADs之间存在某些共性。然而，关于ADs之间相似性的理论研究仍然有限。在这项工作中，我们首先基于网络相似性（NetSim）、功能相似性（FunSim）和语义相似性（SemSim）这三种测量方法，计算了26种ADs之间的遗传相似性，并系统地识别出三对显著相似的ADs：类风湿性关节炎（RA）和系统性红斑狼疮（SLE）、重症肌无力（MG）和自身免疫性甲状腺炎（AIT）、自身免疫性多内分泌腺病（AP）和葡萄膜脑膜脑炎综合征（小柳原田综合征，VKH）。然后，我们通过功能分析研究了这三对显著的ADs所富集的基因本体术语和通路。通过对26种ADs的相似性矩阵进行聚类分析，我们将这三对显著的ADs分别嵌入到三个不同的疾病簇中，每个疾病簇中的ADs可能具有较高的遗传相似性。我们还检测了属于同一疾病簇的ADs中共同存在的风险基因。总体而言，我们的研究结果将为不同ADs在遗传学方面的共性提供重要见解，并有助于发现新的生物标志物以及开发针对ADs的新治疗方法。
