联合气道变应性疾病和阿尔茨海默病共享生物标志物和机制的综合生物信息学分析

IF 1 Q4 GENETICS & HEREDITY
Ken Chen , Yixing Huang , Qimei Bao , Yun Gao , Xudong Zhao , Yin Shi , Xiangdong Cheng , Zu Ye , Yaoshu Teng
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引用次数: 0

摘要

阿尔茨海默病(AD)是痴呆症的主要原因,而联合气道过敏性疾病(UAAD)影响上呼吸道和下呼吸道。流行病学研究表明,患有过敏性疾病的人患AD的风险更高,这暗示了共同的分子机制。本研究旨在确定这两种疾病的关键分子生物标志物,并揭示潜在的机制。AD和UAAD数据来自GEO数据库。加权基因共表达网络分析(WGCNA)鉴定了差异表达的疾病相关基因(DEDRGs)。随后对基因功能进行功能富集分析。采用单样本GSEA (ssGSEA)计算基因集评分。采用LASSO回归建立诊断模型。通过CIBERSORT和ESTIMATE算法预测免疫浸润。机器学习和蛋白质-蛋白质相互作用鉴定了关键基因,并通过RT-qPCR在小鼠模型的气道和脑组织中进行了验证。本研究发现GATA2、SLC39A8和AR是与这两种疾病密切相关的关键基因。诊断模型表现出高性能,RT-qPCR结果证实这些基因在疾病组中共表达水平升高。GATA2已经成为一个关键基因,参与免疫系统激活和JAK-STAT通路。本研究建立了一个包含GATA2、SLC39A8和AR的诊断模型,突出了它们在免疫浸润和疾病进展中的作用,尤其是GATA2。这些发现表明AD和UAAD之间存在共同的机制,为未来的研究和治疗提供了新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Integrated bioinformatics analysis of shared biomarkers and mechanisms in united airway allergic disease and Alzheimer's disease

Integrated bioinformatics analysis of shared biomarkers and mechanisms in united airway allergic disease and Alzheimer's disease
Alzheimer's disease (AD) is a leading cause of dementia, whereas united airway allergic disease (UAAD) affects both the upper and lower airways. Epidemiological studies suggest a higher risk of AD in individuals with allergic diseases, hinting at shared molecular mechanisms. This study aims to identify key molecular biomarkers for both diseases and uncover potential mechanisms. Data for AD and UAAD were obtained from the GEO database. Weighted gene co-expression network analysis (WGCNA) identified differentially expressed disease-related genes (DEDRGs). Functional enrichment analysis was subsequently performed for gene functions. Single-sample GSEA (ssGSEA) was used to calculate gene set scores. LASSO regression was used to establish a diagnostic model. Immune infiltration was predicted via the CIBERSORT and ESTIMATE algorithms. Machine learning and protein-protein interactions identified key genes, which were validated through RT-qPCR in airway and brain tissues from mouse models. This study identified GATA2, SLC39A8, and AR as key genes, which were strongly correlated with both diseases. The diagnostic models demonstrated high performance, and RT-qPCR results confirmed elevated co-expression levels of these genes in the disease groups. GATA2 has emerged as a crucial gene, involved in immune system activation and the JAK-STAT pathway. This study developed a diagnostic model incorporating GATA2, SLC39A8, and AR, highlighting their role in immune infiltration and disease progression, especially GATA2. These findings suggest a shared mechanism between AD and UAAD, offering new targets for future research and therapy.
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来源期刊
Gene Reports
Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍: Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.
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