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基于单细胞 RNA 测序和 RNA 测序数据的新型脓毒症预后模型鉴定及可能药物应用前景分析。

Identification of a novel sepsis prognosis model and analysis of possible drug application prospects: Based on scRNA-seq and RNA-seq data.

机构信息

Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

出版信息

Front Immunol. 2022 Oct 28;13:888891. doi: 10.3389/fimmu.2022.888891. eCollection 2022.

Abstract

Sepsis is a disease with a high morbidity and mortality rate. At present, there is a lack of ideal biomarker prognostic models for sepsis and promising studies using prognostic models to predict and guide the clinical use of medications. In this study, 71 differentially expressed genes (DEGs) were obtained by analyzing single-cell RNA sequencing (scRNA-seq) and transcriptome RNA-seq data, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were performed on these genes. Then, a prognosis model with CCL5, HBD, IFR2BP2, LTB, and WFDC1 as prognostic signatures was successfully constructed after univariate LASSO regression analysis and multivariate Cox regression analysis. Kaplan-Meier (K-M) survival analysis, receiver operating characteristic (ROC) time curve analysis, internal validation, and principal component analysis (PCA) further validated the model for its high stability and predictive power. Furthermore, based on a risk prediction model, gene set enrichment analysis (GSEA) showed that multiple cellular functions and immune function signaling pathways were significantly different between the high- and low-risk groups. In-depth analysis of the distribution of immune cells in healthy individuals and sepsis patients using scRNA-seq data revealed immunosuppression in sepsis patients and differences in the abundance of immune cells between the high- and low-risk groups. Finally, the genetic targets of immunosuppression-related drugs were used to accurately predict the potential use of clinical agents in high-risk patients with sepsis.

摘要

脓毒症是一种发病率和死亡率都很高的疾病。目前,缺乏理想的脓毒症生物标志物预后模型,有前景的研究使用预后模型来预测和指导药物的临床应用。在这项研究中,通过分析单细胞 RNA 测序 (scRNA-seq) 和转录组 RNA-seq 数据,获得了 71 个差异表达基因 (DEGs),并对这些基因进行了基因本体 (GO) 和京都基因与基因组百科全书 (KEGG) 富集途径分析。然后,通过单因素 LASSO 回归分析和多因素 Cox 回归分析,成功构建了以 CCL5、HBD、IFR2BP2、LTB 和 WFDC1 为预后特征的预后模型。Kaplan-Meier (K-M) 生存分析、受试者工作特征 (ROC) 时间曲线分析、内部验证和主成分分析 (PCA) 进一步验证了该模型具有较高的稳定性和预测能力。此外,基于风险预测模型,基因集富集分析 (GSEA) 显示,高低风险组之间的多个细胞功能和免疫功能信号通路存在显著差异。使用 scRNA-seq 数据深入分析健康个体和脓毒症患者的免疫细胞分布,发现脓毒症患者存在免疫抑制,高低风险组之间免疫细胞的丰度存在差异。最后,使用免疫抑制相关药物的遗传靶点,准确预测高危脓毒症患者临床药物的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6966/9650379/4b85ab7738d0/fimmu-13-888891-g001.jpg

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