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通过多种机器学习和分子对接筛选干燥综合征的诊断标志物和潜在治疗药物。

Diagnostic markers and potential therapeutic agents for Sjögren's syndrome screened through multiple machine learning and molecular docking.

机构信息

Department of Rheumatology and Immunology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.

Department of Central Laboratory, Zhengzhou University, Luoyang Central Hospital, Luoyang, China.

出版信息

Clin Exp Immunol. 2023 Jun 5;212(3):224-238. doi: 10.1093/cei/uxad037.

Abstract

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, which mainly damages patients' exocrine glands. Sensitive early diagnostic indicators and effective treatments for pSS are lacking. Using machine learning methods to find diagnostic markers and effective therapeutic ways for pSS is of great significance. In our study, first, 1643 differentially expressed genes (DEGs; 737 were upregulated and 906 were downregulated) were ultimately screened out and analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes based on the datasets from the Gene Expression Omnibus. Then, support vector machine, least absolute shrinkage and selection operator regression, random forest, and weighted correlation network analysis were used to screen out feature genes from DEGs. Subsequently, the intersection of the feature genes was taken to screen 10 genes as hub genes. Meanwhile, the analysis of the diagnostic efficiency of 10 hub genes showed their good diagnostic value for pSS, which was validated through immunohistochemistry on the paraffin sections of the labial gland. Subsequently, a multi-factor regulatory network and correlation analysis of hub genes were performed, and the results showed that ELAVL1 and IGF1R were positively correlated with each other but both negatively correlated with the other seven hub genes. Moreover, several meaningful results were detected through the immune infiltration landscape. Finally, we used molecular docking to screen potential therapeutic compounds of pSS based on the hub genes. We found that the small molecules DB08006, DB08036, and DB15308 had good docking scores with ELAVL1 and IGF1R simultaneously. Our study might provide effective diagnostic biomarkers and new therapeutic ideas for pSS.

摘要

原发性干燥综合征(pSS)是一种慢性炎症性自身免疫性疾病,主要损害患者的外分泌腺。目前缺乏针对 pSS 的敏感早期诊断指标和有效治疗方法。利用机器学习方法寻找 pSS 的诊断标志物和有效治疗方法具有重要意义。在我们的研究中,首先,基于 Gene Expression Omnibus 中的数据集,通过基因本体论和京都基因与基因组百科全书对差异表达基因(DEGs;737 个上调,906 个下调)进行最终筛选和分析。然后,采用支持向量机、最小绝对收缩和选择算子回归、随机森林和加权相关网络分析从 DEGs 中筛选特征基因。随后,取特征基因的交集,筛选出 10 个基因作为枢纽基因。同时,对 10 个枢纽基因的诊断效率分析表明,它们对 pSS 具有良好的诊断价值,通过对唇腺石蜡切片的免疫组化验证了这一点。随后,对枢纽基因进行了多因素调控网络和相关性分析,结果表明,ELAVL1 和 IGF1R 相互之间呈正相关,但与其他七个枢纽基因均呈负相关。此外,通过免疫浸润景观还检测到了一些有意义的结果。最后,我们基于枢纽基因筛选了 pSS 的潜在治疗化合物,通过分子对接发现小分子 DB08006、DB08036 和 DB15308 与 ELAVL1 和 IGF1R 同时具有良好的对接评分。我们的研究可能为 pSS 提供有效的诊断生物标志物和新的治疗思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4adb/10243915/6d5e9425141a/uxad037_fig10.jpg

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