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解读烟酰胺代谢和黑色素相关基因在急性心肌梗死中的作用:一种整合生物信息学分析的机器学习方法

Deciphering the role of nicotinamide metabolism and melanin-related genes in acute myocardial infarction: a machine learning approach integrating bioinformatics analysis.

作者信息

Li Jun, Li Chao, Qian Tao

机构信息

Department of Cardiology, Jinhua People's Hospital, Jinhua, Zhejiang 321000, China.

出版信息

Korean J Physiol Pharmacol. 2025 Jul 1;29(4):521-532. doi: 10.4196/kjpp.24.431. Epub 2025 May 26.

Abstract

Acute myocardial infarction (AMI) represents a significant global mortality factor. Alterations in nicotinamide metabolism within the myocardium post-AMI can influence the progression of the condition. Additionally, melanin plays a crucial role in nicotinamide metabolism and exhibits anti-inflammatory properties. Nevertheless, the diagnostic biomarkers for AMI that are based on nicotinamide metabolism and melanin-associated genes remain poorly defined. In this study, the AMI transcriptomic data from the Gene Expression Omnibus were analyzed to identify differentially expressed genes (DEGs) intersecting with nicotinamide metabolism and melatonin-related genes. Machine learning algorithms, including RandomForest, least absolute shrinkage and selection operator, and support vector machine-recursive feature elimination, were applied to select feature genes. Diagnostic markers were further evaluated based on area under the curve from receiver operating characteristic analysis. We identified 14 candidate genes, refined to 4 key genes, with NAMPT and BST1 ultimately selected as diagnostic biomarkers. These were used to classify AMI into two molecular subtypes. Immune landscape analysis revealed increased infiltration of monocytes, neutrophils, macrophages, and parainflammation in AMI. Enrichment analyses showed DEGs were mainly involved in innate immune response and cytokine production. Additionally, hsa-miR-34a-5p and hsa-miR-181b-5p were identified as potential regulators of NAMPT and BST1. In summary, NAMPT and BST1 are promising diagnostic biomarkers associated with nicotinamide metabolism and melatonin in AMI. The molecular subtyping based on these genes will enhance the management and hierarchical treatment of AMI, offering significant implications for clinical diagnosis and therapeutic strategies.

摘要

急性心肌梗死(AMI)是一个重要的全球死亡因素。AMI后心肌内烟酰胺代谢的改变会影响病情的发展。此外,黑色素在烟酰胺代谢中起关键作用,并具有抗炎特性。然而,基于烟酰胺代谢和黑色素相关基因的AMI诊断生物标志物仍不明确。在本研究中,分析了来自基因表达综合数据库的AMI转录组数据,以鉴定与烟酰胺代谢和褪黑素相关基因相交的差异表达基因(DEG)。应用包括随机森林、最小绝对收缩和选择算子以及支持向量机递归特征消除在内的机器学习算法来选择特征基因。基于受试者工作特征分析的曲线下面积进一步评估诊断标志物。我们鉴定出14个候选基因,精炼为4个关键基因,最终选择NAMPT和BST1作为诊断生物标志物。这些基因被用于将AMI分为两种分子亚型。免疫景观分析显示AMI中单核细胞、中性粒细胞、巨噬细胞浸润增加以及副炎症反应。富集分析表明DEG主要参与先天免疫反应和细胞因子产生。此外,hsa-miR-34a-5p和hsa-miR-181b-5p被鉴定为NAMPT和BST1的潜在调节因子。总之,NAMPT和BST1是与AMI中烟酰胺代谢和褪黑素相关的有前景的诊断生物标志物。基于这些基因的分子亚型分类将加强AMI的管理和分层治疗,对临床诊断和治疗策略具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17c7/12198448/b25593ca5a4b/kjpp-29-4-521-f1.jpg

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