Abstract: Background　Coronary heart disease （CHD） is a serious health issue among middle-aged and elderly people.Inflammation and immune response plays a vital role in occurrence，progression and prognosis of CHD.Toll-like receptors （TLRs） are known to mediate innate and acquired immune responses.Previous studies have shown that TLR2 and TLR4 receptor pathways are associated with CHD，while the relationship between TLRs pathways and other TLRs subtypes and CHD remains to be further studied.Objective　To identify the relationship between TLRs pathways and other TLRs subtypes and CHD，so as to identify the role of TLRs signaling pathway in the process of CHD and find new CHD-related protein.This study would provide a new candidate target for the treatment of CHD.Methods　We used the semantic similarity method based on GO database，and performed functional analysis between the gene sets from March 2016 to February 2018.First，we found the relationship of TLRs signaling pathways with CHD and then followed protein-protein interaction network to analyze the function of targeted proteins.Further，we determined the relationship of TLRs subtypes with CHD based on the number of known CHD-related proteins interacting with the tested proteins.Results　Study results showed that the similarity score of immune system was the highest in seven system pathways of KEGG database.Functional similarity score of TLRs signaling pathway gene set and CHD gene set was higher than that of random gene set （P<0.05）．In fourteen immune system pathways，the functional similarity score of TLRs signaling pathway was the highest.We also observed close interaction between TLR10 and disease-related proteins using analysis of protein-protein interaction network besides TLR2 and TLR4.Conclusion　TLRs signaling pathway plays a crucial role in the process of CHD and the TLRs family may be a new target for the prevention and treatment of CHD.TLR10 could be a new CHD-related protein.

Key words: Coronary disease, Toll-like receptors, Computational biology, Semantic similarity method, Protein interaction maps

摘要： 背景　冠心病严重威胁着中老年人的健康，在其发生、发展以及预后过程中炎症和免疫反应起着非常重要的作用。而Toll样受体（TLRs）能够介导天然免疫和获得性免疫反应，已有研究表明TLR2和TLR4信号通路与冠心病关系密切，但整个TLRs信号通路及其他亚型与冠心病的关系还有待进一步研究。目的　研究TLRs信号通路及其亚型与冠心病的关系，以利于深入研究TLRs信号通路与冠心病的关系，发现新的冠心病相关蛋白，为研发治疗冠心病的药物提供新的候选靶点。方法　2016年3月—2018年2月，基于GO数据库，利用语义相似性方法进行基因集合间功能的一致性分析，获得TLRs信号通路与冠心病的关系。利用蛋白互作网分析待测蛋白质的功能，根据与待测蛋白质互作的已知冠心病相关蛋白的数目，确定TLRs各亚型与冠心病的关系。结果　京都基因与基因组百科全书（KEGG）数据库的7类系统信号通路中，免疫系统信号通路的相似性得分最高。TLRs信号通路基因集合与冠心病基因集合功能相似性得分高于随机情况下两个基因集合的功能相似性得分（P<0.05）。14条免疫系统的信号通路中，TLRs信号通路的功能相似性得分最高。通过蛋白互作网的分析，发现除已知的TLR2、TLR4外，TLR10也与冠心病相关蛋白互作密切。结论　TLRs信号通路与冠心病关系密切，而TLRs家族可能是冠心病防治的新靶点，其中TLR10可能是新的冠心病相关蛋白。

关键词: 冠心病, Toll样受体, 计算生物学, 语义相似性, 蛋白质相互作用图