Integrated multi-omics analysis and machine learning developed diagnostic markers and prognostic model based on Efferocytosis-associated signatures for septic cardiomyopathy

IF 4.5 3区 医学 Q2 IMMUNOLOGY Clinical immunology Pub Date : 2024-06-27 DOI:10.1016/j.clim.2024.110301
Xuelian Li , Shijiu Jiang , Boyuan Wang , Shaolin He , Xiaopeng Guo , Jibin Lin , Yumiao Wei
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Abstract

Septic cardiomyopathy (SCM) is characterized by an abnormal inflammatory response and increased mortality. The role of efferocytosis in SCM is not well understood. We used integrated multi-omics analysis to explore the clinical and genetic roles of efferocytosis in SCM. We identified six module genes (ATP11C, CD36, CEBPB, MAPK3, MAPKAPK2, PECAM1) strongly associated with SCM, leading to an accurate predictive model. Subgroups defined by EFFscore exhibited distinct clinical features and immune infiltration levels. Survival analysis showed that the C1 subtype with a lower EFFscore had better survival outcomes. scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from sepsis patients identified four genes (CEBPB, CD36, PECAM1, MAPKAPK2) associated with high EFFscores, highlighting their role in SCM. Molecular docking confirmed interactions between diagnostic genes and tamibarotene. Experimental validation supported our computational results. In conclusion, our study identifies a novel efferocytosis-related SCM subtype and diagnostic biomarkers, offering new insights for clinical diagnosis and therapy.

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综合多组学分析和机器学习,开发出基于埃弗细胞增多症相关特征的脓毒性心肌病诊断标记和预后模型。
化脓性心肌病(SCM)的特点是炎症反应异常和死亡率升高。流出细胞在 SCM 中的作用尚不十分清楚。我们利用综合多组学分析探索了流出细胞在 SCM 中的临床和遗传作用。我们发现了六个与 SCM 密切相关的模块基因(ATP11C、CD36、CEBPB、MAPK3、MAPKAPK2 和 PECAM1),从而建立了一个准确的预测模型。根据 EFFscore 定义的亚组表现出不同的临床特征和免疫浸润水平。脓毒症患者外周血单核细胞(PBMCs)的 scRNA-seq 分析发现了四个与高 EFFscores 相关的基因(CEBPB、CD36、PECAM1、MAPKAPK2),突显了它们在 SCM 中的作用。分子对接证实了诊断基因与他米巴罗汀之间的相互作用。实验验证支持了我们的计算结果。总之,我们的研究发现了一种新的与流出相关的 SCM 亚型和诊断生物标志物,为临床诊断和治疗提供了新的见解。
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来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
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