School of Clinical Medicine, Tsinghua University, Beijing 100190, China.
Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 100084, China.
Int J Mol Sci. 2023 Sep 29;24(19):14720. doi: 10.3390/ijms241914720.
Sepsis, a disease caused by severe infection, has a high mortality rate. At present, there is a lack of reliable algorithmic models for biomarker mining and diagnostic model construction for sepsis. Programmed cell death (PCD) has been shown to play a vital role in disease occurrence and progression, and different PCD-related genes have the potential to be targeted for the treatment of sepsis. In this paper, we analyzed PCD-related genes in sepsis. Implicated PCD processes include apoptosis, necroptosis, ferroptosis, pyroptosis, netotic cell death, entotic cell death, lysosome-dependent cell death, parthanatos, autophagy-dependent cell death, oxeiptosis, and alkaliptosis. We screened for diagnostic-related genes and constructed models for diagnosing sepsis using multiple machine-learning models. In addition, the immune landscape of sepsis was analyzed based on the diagnosis-related genes that were obtained. In this paper, 10 diagnosis-related genes were screened for using machine learning algorithms, and diagnostic models were constructed. The diagnostic model was validated in the internal and external test sets, and the Area Under Curve (AUC) reached 0.7951 in the internal test set and 0.9627 in the external test set. Furthermore, we verified the diagnostic gene via a qPCR experiment. The diagnostic-related genes and diagnostic genes obtained in this paper can be utilized as a reference for clinical sepsis diagnosis. The results of this study can act as a reference for the clinical diagnosis of sepsis and for target discovery for potential therapeutic drugs.
脓毒症是一种由严重感染引起的疾病,死亡率很高。目前,缺乏可靠的算法模型来挖掘生物标志物和构建脓毒症诊断模型。程序性细胞死亡(PCD)已被证明在疾病的发生和发展中起着至关重要的作用,不同的与 PCD 相关的基因有可能成为脓毒症治疗的靶点。在本文中,我们分析了脓毒症中的 PCD 相关基因。涉及的 PCD 过程包括细胞凋亡、坏死性凋亡、铁死亡、细胞焦亡、细胞坏死、自噬依赖性细胞死亡、细胞自噬、细胞程序性坏死、细胞内溶酶体依赖的细胞死亡、过氧化物酶体依赖性细胞死亡和碱中毒。我们使用多种机器学习模型筛选了与诊断相关的基因,并构建了用于诊断脓毒症的模型。此外,还基于获得的诊断相关基因分析了脓毒症的免疫景观。本文使用机器学习算法筛选出 10 个诊断相关基因,并构建了诊断模型。该诊断模型在内、外部测试集中进行了验证,内部测试集的 AUC 达到 0.7951,外部测试集的 AUC 达到 0.9627。此外,我们通过 qPCR 实验验证了诊断基因。本文获得的诊断相关基因和诊断基因可作为临床脓毒症诊断的参考。本研究结果可作为脓毒症临床诊断的参考,也可作为潜在治疗药物靶点的发现参考。
Biochim Biophys Acta Mol Basis Dis. 2024-8
Immunopharmacol Immunotoxicol. 2023-12
Front Immunol. 2023