整合孟德尔随机化和机器学习来识别COPD中与缺氧相关的诊断生物标志物和因果关系。

IF 3.1 3区 医学 Q2 RESPIRATORY SYSTEM
Wenhui Fu, Yangli Liu, Renjie Li, Haiying Jin
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引用次数: 0

摘要

背景:慢性阻塞性肺疾病(Chronic obstructive pulmonary disease, COPD)是一种进行性肺功能下降的疾病,缺氧在其发病过程中起着关键作用。然而,针对COPD中缺氧相关基因(HRGs)的系统研究仍然有限。方法:我们应用机器学习识别hrg相关的诊断性生物标志物,并通过受试者工作特征(ROC)分析评估其性能。采用孟德尔随机化(MR)评估候选基因与COPD之间的因果关系。构建nomogram模型评估临床应用价值,并利用ENCORI数据库建立ceRNA网络。结果:共鉴定出6个基于hrg的诊断性生物标志物,其中SLC2A1具有较强的诊断价值(AUC >.8)。MR分析显示SLC2A1表达与COPD风险有显著的因果关系(OR = 1.32, 95% CI: 1.02 ~ 1.71, P < 0.05)。功能证据表明,SLC2A1促进缺氧诱导的气道上皮细胞代谢重编程。所构建的图具有较好的临床适用性。ceRNA分析强调MALAT1、NEAT1和XIST是潜在的上游调控因子。结论:我们的研究结果确定SLC2A1是COPD的病因和诊断相关基因,为缺氧驱动的疾病机制提供了新的见解,并支持未来的个性化治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrating Mendelian Randomization and Machine Learning to Identify Hypoxia-Related Diagnostic Biomarkers and Causal Relationship in COPD.

Background: Chronic obstructive pulmonary disease (COPD) involves progressive lung function decline, with hypoxia playing a key pathogenic role. However, systematic investigations focusing on hypoxia-related genes (HRGs) in COPD remain limited.

Methods: We applied machine learning to identify HRG-associated diagnostic biomarkers and evaluated their performance via Receiver Operating Characteristic (ROC) analysis. Mendelian randomization (MR) was conducted to assess causal relationships between candidate genes and COPD. A nomogram model was constructed to evaluate clinical utility, and a ceRNA network was developed using ENCORI database.

Results: Six HRG-based diagnostic biomarkers were identified, including SLC2A1, which demonstrated strong diagnostic value (AUC > 0.8). MR analysis revealed a significant causal effect of SLC2A1 expression on COPD risk (OR = 1.32, 95% CI: 1.02-1.71, P < 0.05). Functional evidence suggests SLC2A1 promotes hypoxia-induced metabolic reprogramming in airway epithelial cells. The constructed nomogram showed good clinical applicability. ceRNA analysis highlighted MALAT1, NEAT1, and XIST as potential upstream regulators.

Conclusion: Our findings identify SLC2A1 as a causal and diagnostically relevant gene in COPD, offering novel insight into hypoxia-driven disease mechanisms and supporting future personalized therapeutic strategies.

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来源期刊
CiteScore
4.80
自引率
10.70%
发文量
372
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed journal of therapeutics and pharmacology focusing on concise rapid reporting of clinical studies and reviews in COPD. Special focus will be given to the pathophysiological processes underlying the disease, intervention programs, patient focused education, and self management protocols. This journal is directed at specialists and healthcare professionals
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