酒精使用障碍和精神分裂症共同表达的核心基因筛选和潜在分子机制分析
Analysis of potentially co-expressed hub genes and molecular mechanism for alcohol use disorders and schizophrenia based on bioinformatics method core gene screening and molecular mechanism analysis
朱有为 1赵容 1苏杭 1钟娜 1江海峰 1杜江 1赵敏1
作者信息
- 1. 200030 上海交通大学医学院附属精神卫生中心
- 折叠
摘要
目的:应用生物信息学方法筛选酒精使用障碍(AUD)和精神分裂症(SCZ)具有共同表达趋势的关键基因和相关分子机制.方法:从基因表达综合数据库下载AUD基因表达数据集GSE161986以及SCZ基因表达数据集GSE53987、GSE17162 和GSE21138.对上述基因表达数据集进行标准化处理并筛选在AUD和SCZ中均存在显著差异表达基因(DEGs).使用注释可视化与综合发现数据库(DA-VID)对筛选到的DEGs进行富集分析,使用相互作用基因的搜索工具数据库(STRING)和Cytoscape软件进行蛋白-蛋白互作(PPI)网络构建并筛选两种疾病共有的关键基因.使用AUD芯片数据集GSE44456 和SCZ芯片数据集GSE87610 对筛选出的潜在核心基因进行验证分析.结果:共筛选出95 个DEGs,表达上调的DEGs主要参与凋亡过程的负调控和NF-kappa B信号通路调控;表达下调的DEGs主要参与化学突触传递和神经活性配体-受体相互作用通路.金属硫蛋白基因(MTIG)、MT2A和微白蛋白基因(PVALB)可能是AUD和SCZ共病以及导致酒精所致精神障碍发病的潜在关键基因.结论:MTIG、MT2A和PVALB表达异常可能在AUD和SCZ共病及酒精所致精神障碍的发病过程中起到关键作用,并可能作为上述相关疾病诊断和治疗的潜在分子靶标.
Abstract
Objective:To investigate the common gene expression characteristic and molecular mechanism of alcohol use disorder(AUD)and schizophrenia(SCZ)using bioinformatics methods.Method:The AUD gene expression dataset GSE161986 as well as SCZ gene expression datasets GSE53987,GSE17162,and GSE21138 were downloaded from Gene Expression Omnibus(GEO)database.Data normalization and Differentially Ex-pressed Genes(DEGs)screening were carried out both in AUD and SCZ datasets.Based on these DEGs,function-al annotation and pathway analysis were performed using the Database for Annotation,Visualization and Integrated Discovery(DAVID).Protein-Protein Interaction(PPI)network construction and key genes screening were ana-lyzed using the Search Tool for the Retrieval of Interacting Genes(STRING)database and Cytoscape software.GSE44456 and GSE87610 were applied for potential core genes validation.Results:A total of 95 DEGs were i-dentified.Functional annotation and pathway analysis indicated that up-regulated DEGs were mainly involved in negative regulation of apoptosis and NF-kappa B signal pathway.Down-regulated DEGs were mainly related to chemical synaptic transmission and neuroactive ligand-receptor interaction pathways.Metallothionein gene(MTIG),MT2A,and parvalbumin(PVALB)may played a key role in the co-occurrence of AUD and SCZ and the pathogenesis of alcohol-induced mental disorders.Conclusion:Aberrant expression of MTIG,MT2A,and PVALB may play a key role in the co-occurrence of AUD and SCZ,as well as the pathogenesis of alcohol-induced mental disorders.These genes may serve as potential molecular targets for the prevention and treatment of these related diseases.
关键词
酒精使用障碍/精神分裂症/差异表达基因/核心基因Key words
alcohol use disorder/schizophrenia/differentially expressed genes/hub genes引用本文复制引用
基金项目
国家自然科学基金(82130041)
国家自然科学基金(82171485)
科技创新2030重大项目(2021ZD0202105)
上海市精神卫生中心"飞翔计划"(2022-FX-01)
出版年
2024
NETL
NSTL
万方数据