探讨巨噬细胞相关基因在动脉粥样硬化中的分子功能和免疫相关性

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Chenchen Yu, Haoran Wang, Huiting Xu, Peipei Kang, Jingjing Shao, Hui Zhang
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引用次数: 0

摘要

动脉粥样硬化是一种常见且重要的心血管疾病,传统的诊断和治疗技术往往无法诊断,直到它发展到更严重的阶段。这一挑战阻碍了实施早期发现和干预措施的能力。因此,创造创新和更准确的生物标志物至关重要。该研究首先通过单细胞分析识别巨噬细胞相关基因,研究其功能。随后,各种机器学习方法被用于识别巨噬细胞相关的重要调控基因。此外,还进行了分子对接研究,以评估这些关键标志物与动脉粥样硬化治疗药物的结合亲和力。ImmuCellAI平台还用于评估动脉粥样硬化样本中的免疫细胞评分,帮助检查重要诊断标志物与免疫细胞之间的联系。最后,采用qRT-PCR和Western blot方法对所选关键基因的表达变化进行验证。通过单细胞水平的分析和差异评估,我们发现了58个与巨噬细胞相关的基因表现出差异表达。功能评估表明,这些基因与免疫微环境之间存在很强的相关性。通过聚类分析,我们评估了不同亚组动脉粥样硬化患者对免疫治疗的反应。利用XGBoost、随机森林和GOsemsim算法等技术,我们确定了五个关键的诊断标记。分子对接研究证实,这些重要标记物可作为动脉粥样硬化的潜在药物靶点。最后,我们的实验分析显示,这五种诊断标记在动脉粥样硬化组织中显著过表达。本研究介绍了与动脉粥样硬化中巨噬细胞相关的新诊断指标,并强调了巨噬细胞作为免疫系统相关治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exploring the Molecular Functions and Immune Relevance of Macrophage-Associated Genes in Atherosclerosis

Exploring the Molecular Functions and Immune Relevance of Macrophage-Associated Genes in Atherosclerosis

Atherosclerosis is a common and significant cardiovascular condition that frequently goes undiagnosed by conventional diagnostic and treatment techniques until it reaches a more advanced stage. This challenge impedes the capacity to apply early detection and intervention measures. As a result, the creation of innovative and more accurate biomarkers is critically important. The study first recognizes genes associated with macrophages through single-cell analysis, investigating their functions. Subsequently, various machine learning approaches are utilized to identify significant regulatory genes related to macrophages. In addition, molecular docking studies are performed to evaluate the binding affinity of these crucial markers with therapeutics targeting atherosclerosis. The ImmuCellAI platform is also utilized to assess immune cell scores in atherosclerotic samples, aiding in the examination of connections between vital diagnostic markers and immune cells. Finally, the expression changes of the selected key genes are confirmed using qRT-PCR and Western blot methods. Through analyses at the single-cell level and differential assessments, we discovered 58 genes related to macrophages that exhibited differential expression. Functional evaluations indicated a strong correlation between these genes and the immune microenvironment. By conducting cluster analysis, we assessed how different subgroups of patients with atherosclerosis respond to immunotherapy. Utilizing techniques such as XGBoost, random forest, and the GOsemsim algorithm, we pinpointed five crucial diagnostic markers. Studies on molecular docking validated that these important markers could act as potential drug targets for atherosclerosis. Finally, our experimental analysis revealed a significant overexpression of these five diagnostic markers in tissues affected by atherosclerosis. This research introduces novel diagnostic indicators associated with macrophages in atherosclerosis and emphasizes their potential as targets for therapies related to the immune system.

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来源期刊
Human Mutation
Human Mutation 医学-遗传学
CiteScore
8.40
自引率
5.10%
发文量
190
审稿时长
2 months
期刊介绍: Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.
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