解码痴呆机制:通过整合生物信息学和机器学习鉴定关键少突胶质细胞相关基因。

IF 3.3 4区 医学 Q3 CHEMISTRY, MEDICINAL
Yan Chen, Hao Wen, Xinyi Qiu, Chen Li, Yinhui Yao, Yazhen Shang
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引用次数: 0

摘要

本研究旨在利用生物信息学分析和机器学习算法阐明痴呆的机制,为其临床管理确定新的治疗靶点。方法:与痴呆相关的基因表达数据集来源于GEO数据库。差异表达基因(DEGs)通过R进行鉴定,关键模块基因通过加权基因共表达网络分析(WGCNA)方法确定。从GeneCards数据库检索少突胶质细胞(OL)相关靶点。使用基因本体和京都基因与基因组百科全书对DEGs、WGCNA和OL的交叉基因进行分析。随后,使用了三种机器学习算法来确定与痴呆中OL相关的核心基因。使用CIBERSORT算法评估22种免疫细胞类型的丰度及其与痴呆相关免疫浸润的相关性。通过定量反转录聚合酶链反应(RT-qPCR)进行验证。结果:通过生物信息学和机器学习技术,鉴定出6个与痴呆相关的核心OL基因,其中C1QA、CD163和TGFB2在痴呆中表达升高。免疫细胞浸润分析表明,多种免疫细胞类型可能参与痴呆的发病机制,RT-qPCR结果证实了生物信息学的发现。讨论:发现的基因可能通过少突胶质细胞功能障碍和神经免疫相互作用参与痴呆发病。值得注意的是,TGFB2和补体相关基因(C1QA, CD163)表明它们参与髓鞘形成缺陷和神经炎症,突出了它们的治疗潜力。结论:TGFB2、C1QA、CD163、ACTG1、WIF1、OPALIN 6个特征基因与痴呆有显著相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Decoding Dementia Mechanisms: Identification of Key Oligodendrocyte-Associated Genes through Integrative Bioinformatics and Machine Learning.

Introduction: This study aims to elucidate the mechanisms underlying Dementia using bioinformatics analysis and machine learning algorithms, to identify novel therapeutic targets for its clinical management.

Methods: Gene expression datasets related to dementia were sourced from the GEO database. Differentially expressed genes (DEGs) were identified using R, and key module genes were determined through the Weighted Gene Co-expression Network Analysis (WGCNA) method. Oligodendrocyte (OL) related targets were retrieved from the GeneCards database. The intersecting genes from DEGs, WGCNA, and OL were analyzed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Subsequently, three machine learning algorithms were employed to pinpoint core genes associated with OL in dementia. The CIBERSORT algorithm was used to evaluate the abundance of 22 immune cell types and their correlation with Dementia-related immune infiltration. Validation was carried out via quantitative reverse transcription polymerase chain reaction (RT-qPCR).

Results: Through bioinformatics and machine learning techniques, six core OL genes associated with Dementia were identified, notably C1QA, CD163, and TGFB2, which showed elevated expression in Dementia. Immune cell infiltration analysis indicated that several immune cell types may contribute to Dementia's pathogenesis, and RT-qPCR results corroborated the bioinformatics findings.

Discussion: The discovered genes may contribute to dementia pathogenesis through oligodendrocyte dysfunction and neuroimmune interactions. Notably, TGFB2 and complement-related genes (C1QA, CD163) suggest involvement in both myelination defects and neuroinflammation, highlighting their therapeutic potential.

Conclusion: The six feature genes: TGFB2, C1QA, CD163, ACTG1, WIF1, and OPALIN are significantly linked to Dementia.

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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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