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解析儿童脓毒症的分子分类:将加权基因共表达网络分析(WGCNA)和基于机器学习的分类与免疫特征相结合,以开发先进的诊断模型。

Deciphering the molecular classification of pediatric sepsis: integrating WGCNA and machine learning-based classification with immune signatures for the development of an advanced diagnostic model.

作者信息

Huang Junming, Chen Jinji, Wang Chengbang, Lai Lichuan, Mi Hua, Chen Shaohua

机构信息

Department of Urology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.

Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

出版信息

Front Genet. 2024 Jan 29;15:1294381. doi: 10.3389/fgene.2024.1294381. eCollection 2024.

Abstract

Pediatric sepsis (PS) is a life-threatening infection associated with high mortality rates, necessitating a deeper understanding of its underlying pathological mechanisms. Recently discovered programmed cell death induced by copper has been implicated in various medical conditions, but its potential involvement in PS remains largely unexplored. We first analyzed the expression patterns of cuproptosis-related genes (CRGs) and assessed the immune landscape of PS using the GSE66099 dataset. Subsequently, PS samples were isolated from the same dataset, and consensus clustering was performed based on differentially expressed CRGs. We applied weighted gene co-expression network analysis to identify hub genes associated with PS and cuproptosis. We observed aberrant expression of 27 CRGs and a specific immune landscape in PS samples. Our findings revealed that patients in the GSE66099 dataset could be categorized into two cuproptosis clusters, each characterized by unique immune landscapes and varying functional classifications or enriched pathways. Among the machine learning approaches, Extreme Gradient Boosting demonstrated optimal performance as a diagnostic model for PS. Our study provides valuable insights into the molecular mechanisms underlying PS, highlighting the involvement of cuproptosis-related genes and immune cell infiltration.

摘要

小儿脓毒症(PS)是一种危及生命的感染,死亡率很高,因此有必要更深入地了解其潜在的病理机制。最近发现的由铜诱导的程序性细胞死亡与多种医学病症有关,但其在PS中的潜在作用在很大程度上仍未得到探索。我们首先分析了铜死亡相关基因(CRGs)的表达模式,并使用GSE66099数据集评估了PS的免疫格局。随后,从同一数据集中分离出PS样本,并基于差异表达的CRGs进行共识聚类。我们应用加权基因共表达网络分析来识别与PS和铜死亡相关的枢纽基因。我们观察到PS样本中27个CRGs的异常表达和特定的免疫格局。我们的研究结果表明,GSE66099数据集中的患者可分为两个铜死亡簇,每个簇具有独特的免疫格局和不同的功能分类或富集途径。在机器学习方法中,极端梯度提升作为PS的诊断模型表现出最佳性能。我们的研究为PS的潜在分子机制提供了有价值的见解,突出了铜死亡相关基因和免疫细胞浸润的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c81/10859440/43747ed10a8a/fgene-15-1294381-g001.jpg

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