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通过单细胞 RNA 测序和荟萃分析鉴定银屑病相关免疫标志物 G3BP2。

Identification of psoriasis-associated immune marker G3BP2 through single-cell RNA sequencing and meta analysis.

机构信息

Department of Dermatology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.

出版信息

Immunology. 2024 Dec;173(4):730-747. doi: 10.1111/imm.13851. Epub 2024 Sep 12.

Abstract

Psoriasis is a chronic skin disease with an increasing prevalence each year. However, the mechanisms underlying its onset and progression remain unclear, and effective therapeutic targets are lacking. Therefore, we employs an innovative approach by combining single-cell RNA sequencing (scRNA-seq) with meta-analysis. This not only elucidates the potential mechanisms of psoriasis at the cellular level but also identifies immunoregulatory marker genes that play a statistically significant role in driving psoriasis progression through comprehensive analysis of multiple datasets. Skin tissue samples from 12 psoriasis patients underwent scRNA-seq, followed by quality control, filtering, PCA dimensionality reduction, and tSNE clustering analysis to identify T cell subtypes and differentially expressed genes (DEGs) in psoriatic skin tissue. Next, three psoriasis datasets were standardised and merged to identify differentially expressed genes (DEGs). Subsequently, weighted gene co-expression network analysis (WGCNA) was applied for clustering analysis of gene co-expression network modules and to assess the correlation between these modules and DEGs. Least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic (ROC) curve analyses were conducted to select disease-specific genes and evaluate their diagnostic value. Single-cell data revealed nine cell types in psoriatic skin tissue, with seven T cell subtypes identified. Intersection analysis identified ADAM8 and G3BP2 as key genes. Through the integration of scRNA-seq and Meta analysis, we identified the immunoregulatory marker gene G3BP2, which is associated with the onset and progression of psoriasis and holds clinical significance. G3BP2 is speculated to promote the development of psoriasis by increasing the proportion of CD8+ T cells.

摘要

银屑病是一种慢性皮肤病,其发病率每年都在增加。然而,其发病和进展的机制尚不清楚,也缺乏有效的治疗靶点。因此,我们采用了一种创新的方法,将单细胞 RNA 测序(scRNA-seq)与荟萃分析相结合。这不仅阐明了银屑病在细胞水平上的潜在机制,还通过对多个数据集的综合分析,确定了在驱动银屑病进展中具有统计学意义的免疫调节标记基因。对 12 名银屑病患者的皮肤组织样本进行 scRNA-seq,然后进行质量控制、过滤、PCA 降维和 tSNE 聚类分析,以鉴定银屑病皮肤组织中的 T 细胞亚群和差异表达基因(DEGs)。接下来,对三个银屑病数据集进行标准化和合并,以鉴定差异表达基因(DEGs)。然后,应用加权基因共表达网络分析(WGCNA)对基因共表达网络模块进行聚类分析,并评估这些模块与 DEGs 的相关性。采用最小绝对收缩和选择算子(LASSO)回归和接收者操作特征(ROC)曲线分析来选择疾病特异性基因,并评估其诊断价值。单细胞数据分析揭示了银屑病皮肤组织中的 9 种细胞类型,其中鉴定出 7 种 T 细胞亚群。交集分析鉴定出 ADAM8 和 G3BP2 为关键基因。通过 scRNA-seq 和 Meta 分析的整合,我们确定了免疫调节标记基因 G3BP2,它与银屑病的发病和进展有关,具有临床意义。推测 G3BP2 通过增加 CD8+T 细胞的比例来促进银屑病的发展。

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