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阿尔茨海默病中基于三个基因的诊断标志物

A 3-Gene-Based Diagnostic Signature in Alzheimer's Disease.

作者信息

Wang Huimin, Zhang Yanqiu, Zheng Chengyao, Yang Songqi, Chen Xiuju, Wang Heng, Gao Sheng

机构信息

Department of Neurology, Tianjin NanKai Hospital, Tianjin, China.

Department of Neurology, Tianjin NanKai Hospital, Tianjin, China,

出版信息

Eur Neurol. 2022;85(1):6-13. doi: 10.1159/000518727. Epub 2021 Sep 14.

DOI:10.1159/000518727
PMID:34521086
Abstract

BACKGROUND

Alzheimer's disease (AD) is a chronic neurodegenerative disease. In this study, potential diagnostic biomarkers were identified for AD.

METHODS

All AD samples and healthy samples were collected from 2 datasets in the GEO database, in which differentially expressed genes (DEGs) were analyzed by using the limma package of R language. GO and KEGG pathway enrichment was conducted basing on the DEGs via the clusterProfiler package of R. And, the PPI network construction and gene prediction were performed using the STRING database and Cytoscape. Then, a logistic regression model was constructed to predict the sample type.

RESULTS

Bioinformatic analysis of GEO datasets revealed 2,063 and 108 DEGs in GSE5281 and GSE4226 datasets, separately, and 15 overlapping DEGs were found. GO and KEGG enrichment analysis revealed terms associated with neurodevelopment. Then, we built a logistic regression model based on the hub genes from the PPI network and optimized the model to 3 genes (ALDOA, ENC1, and NFKBIA). The values of area under the curve of the training set GSE5281 and testing set GSE4226 were 0.9647 and 0.7857, respectively, which implied the efficacy of this model.

CONCLUSION

The comprehensive bioinformatic analysis of gene expression in AD patients and the effective logistic regression model built in our study may provide promising research value for diagnostic methods of AD.

摘要

背景

阿尔茨海默病(AD)是一种慢性神经退行性疾病。在本研究中,确定了AD的潜在诊断生物标志物。

方法

从GEO数据库的2个数据集中收集所有AD样本和健康样本,使用R语言的limma软件包分析差异表达基因(DEG)。基于DEG,通过R语言的clusterProfiler软件包进行GO和KEGG通路富集分析。并且,使用STRING数据库和Cytoscape进行蛋白质-蛋白质相互作用(PPI)网络构建和基因预测。然后,构建逻辑回归模型以预测样本类型。

结果

对GEO数据集的生物信息学分析分别在GSE5281和GSE4226数据集中揭示了2063个和108个DEG,并且发现了15个重叠的DEG。GO和KEGG富集分析揭示了与神经发育相关的术语。然后,我们基于PPI网络中的中心基因构建了逻辑回归模型,并将模型优化为3个基因(醛缩酶A(ALDOA)、上皮细胞转化基因1(ENC1)和核因子κB抑制蛋白α(NFKBIA))。训练集GSE5281和测试集GSE4226的曲线下面积值分别为0.9647和0.7857,这表明该模型的有效性。

结论

对AD患者基因表达的综合生物信息学分析以及我们研究中建立的有效逻辑回归模型可能为AD的诊断方法提供有前景的研究价值。

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