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采用组合生物信息学策略鉴定精神分裂症的潜在生物标志物及其与免疫浸润细胞的相关性。

Identification of potential biomarkers and their correlation with immune infiltration cells in schizophrenia using combinative bioinformatics strategy.

机构信息

Department of Epidemiology and Biostatistics, School of public health, Jilin University, Changchun, 130021, China.

Department of Epidemiology and Biostatistics, School of public health, Jilin University, Changchun, 130021, China.

出版信息

Psychiatry Res. 2022 Aug;314:114658. doi: 10.1016/j.psychres.2022.114658. Epub 2022 May 30.

Abstract

Many studies have identified changes in gene expression in brains of schizophrenia patients and their altered molecular processes, but the findings in different datasets were inconsistent and diverse. Here we performed the most comprehensive analysis of gene expression patterns to explore the underlying mechanisms and the potential biomarkers for early diagnosis in schizophrenia. We focused on 10 gene expression datasets in post-mortem human brain samples of schizophrenia downloaded from gene expression omnibus (GEO) database using the integrated bioinformatics analyses including robust rank aggregation (RRA) algorithm, Weighted gene co-expression network analysis (WGCNA) and CIBERSORT. Machine learning algorithm was used to construct the risk prediction model for early diagnosis of schizophrenia. We identified 15 key genes (SLC1A3, AQP4, GJA1, ALDH1L1, SOX9, SLC4A4, EGR1, NOTCH2, PVALB, ID4, ABCG2, METTL7A, ARC, F3 and EMX2) in schizophrenia by performing multiple bioinformatics analysis algorithms. Moreover, the interesting part of the study is that there is a correlation between the expression of hub genes and the immune infiltrating cells estimated by CIBERSORT. Besides, the risk prediction model was constructed by using both these genes and the immune cells with a high accuracy of 0.83 in the training set, and achieved a high AUC of 0.77 for the test set. Our study identified several potential biomarkers for diagnosis of SCZ based on multiple bioinformatics algorithms, and the constructed risk prediction model using these biomarkers achieved high accuracy. The results provide evidence for an improved understanding of the molecular mechanism of schizophrenia.

摘要

许多研究已经确定了精神分裂症患者大脑中基因表达的变化及其改变的分子过程,但不同数据集的发现并不一致且多种多样。在这里,我们进行了最全面的基因表达模式分析,以探索精神分裂症的潜在机制和早期诊断的潜在生物标志物。我们专注于从基因表达综合数据库(GEO)下载的 10 个人类死后大脑样本的基因表达数据集,使用包括稳健秩聚合(RRA)算法、加权基因共表达网络分析(WGCNA)和 CIBERSORT 在内的综合生物信息学分析。机器学习算法用于构建精神分裂症早期诊断的风险预测模型。我们通过执行多种生物信息学分析算法,确定了 15 个关键基因(SLC1A3、AQP4、GJA1、ALDH1L1、SOX9、SLC4A4、EGR1、NOTCH2、PVALB、ID4、ABCG2、METTL7A、ARC、F3 和 EMX2)在精神分裂症中的作用。此外,研究的有趣之处在于,枢纽基因的表达与 CIBERSORT 估计的免疫浸润细胞之间存在相关性。此外,我们使用这些基因和免疫细胞构建了风险预测模型,在训练集中的准确性高达 0.83,在测试集中的 AUC 达到 0.77。我们的研究基于多种生物信息学算法确定了几个潜在的精神分裂症诊断生物标志物,并且使用这些生物标志物构建的风险预测模型达到了很高的准确性。这些结果为改善对精神分裂症分子机制的理解提供了证据。

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