Employing a synergistic bioinformatics and machine learning framework to elucidate biomarkers associating asthma with pyrimidine metabolism genes.

IF 5.8 2区 医学 Q1 Medicine
Dihui Zhang, Xiaowei Pu, Man Zheng, Guanghui Li, Jia Chen
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引用次数: 0

Abstract

Background: Asthma, a prevalent chronic inflammatory disorder, is shaped by a multifaceted interplay between genetic susceptibilities and environmental exposures. Despite strides in deciphering its pathophysiological landscape, the intricate molecular underpinnings of asthma remain elusive. The focus has increasingly shifted toward the metabolic aberrations accompanying asthma, particularly within the domain of pyrimidine metabolism (PyM)-a critical pathway in nucleotide synthesis and degradation. While the therapeutic relevance of PyM has been recognized across various diseases, its specific contributions to asthma pathology are yet underexplored. This study employs sophisticated bioinformatics approaches to delineate and confirm the involvement of PyM genes (PyMGs) in asthma, aiming to bridge this significant gap in knowledge.

Methods: Employing cutting-edge bioinformatics techniques, this research aimed to elucidate the role of PyMGs in asthma. We conducted a detailed examination of 31 PyMGs to assess their differential expression. Through Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), we explored the biological functions and pathways linked to these genes. We utilized Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) to pinpoint critical hub genes and to ascertain the diagnostic accuracy of eight PyMGs in distinguishing asthma, complemented by an extensive correlation study with the clinical features of the disease. Validation of the gene expressions was performed using datasets GSE76262 and GSE147878.

Results: Our analyses revealed that eleven PyMGs-DHODH, UMPS, NME7, NME1, POLR2B, POLR3B, POLR1C, POLE, ENPP3, RRM2B, TK2-are significantly associated with asthma. These genes play crucial roles in essential biological processes such as RNA splicing, anatomical structure maintenance, and metabolic processes involving purine compounds.

Conclusions: This investigation identifies eleven PyMGs at the core of asthma's pathogenesis, establishing them as potential biomarkers for this disease. Our findings enhance the understanding of asthma's molecular mechanisms and open new avenues for improving diagnostics, monitoring, and progression evaluation. By providing new insights into non-cancerous pathologies, our work introduces a novel perspective and sets the stage for further studies in this field.

采用协同生物信息学和机器学习框架,阐明哮喘与嘧啶代谢基因相关的生物标志物。
背景:哮喘是一种常见的慢性炎症性疾病,是由遗传易感性和环境暴露之间的多方面相互作用形成的。尽管在破译其病理生理结构方面取得了长足进步,但哮喘错综复杂的分子基础仍然难以捉摸。人们越来越关注哮喘伴随的代谢畸变,尤其是嘧啶代谢(PyM)领域--核苷酸合成和降解的关键途径。虽然 PyM 在各种疾病中的治疗意义已得到认可,但其对哮喘病理学的具体贡献尚未得到充分探索。本研究采用先进的生物信息学方法来描述和确认 PyM 基因(PyMGs)参与哮喘的病理过程,旨在弥补这一知识空白:本研究采用最先进的生物信息学技术,旨在阐明 PyMGs 在哮喘中的作用。我们对 31 个 PyMGs 进行了详细研究,以评估它们的差异表达。通过基因组富集分析(Gene Set Enrichment Analysis,GSEA)和基因组变异分析(Gene Set Variation Analysis,GSVA),我们探索了与这些基因相关的生物学功能和通路。我们利用拉索回归(Lasso regression)和支持向量机-递归特征消除(SVM-RFE)来确定关键的枢纽基因,并确定八个 PyMGs 在鉴别哮喘方面的诊断准确性,同时辅以与疾病临床特征的广泛相关性研究。利用数据集 GSE76262 和 GSE147878 对基因表达进行了验证:我们的分析表明,11 个 PyMGs-DHODH、UMPS、NME7、NME1、POLR2B、POLR3B、POLR1C、POLE、ENPP3、RRM2B、TK2 与哮喘显著相关。这些基因在 RNA 剪接、解剖结构维持和涉及嘌呤化合物的代谢过程等重要生物过程中发挥着关键作用:这项研究发现了 11 个处于哮喘发病机制核心的 PyMGs,并将它们确立为该疾病的潜在生物标记物。我们的研究结果加深了人们对哮喘分子机制的了解,为改进诊断、监测和病情发展评估开辟了新途径。通过提供对非癌症病理的新见解,我们的工作引入了一个新的视角,为这一领域的进一步研究奠定了基础。
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来源期刊
Respiratory Research
Respiratory Research RESPIRATORY SYSTEM-
CiteScore
9.70
自引率
1.70%
发文量
314
审稿时长
4-8 weeks
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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