Investigation of key ferroptosis-associated genes and potential therapeutic drugs for asthma based on machine learning and regression models.

Journal: Scientific reports
Published Date:

Abstract

Bronchial asthma is a complex and heterogeneous disease, with ferroptosis, a form of non-apoptotic cell death, contributing to its pathogenesis by inducing airway epithelial damage, inflammatory infiltration, and airway remodeling. Investigating ferroptosis-related characteristic genes and potential therapeutic compounds may enhance asthma management. This study employed differential analysis and machine learning to identify ferroptosis-related characteristic genes in asthma using the GSE179156 dataset and FerrDb V2 database. Immune infiltration analysis explored the associations between these genes and immune cells, while potential small-molecule drugs were screened through the Connectivity Map (CMap) database and evaluated via molecular docking and molecular dynamics simulations. Two ferroptosis-related characteristic genes, AGPS and APELA, were identified, with AGPS upregulated and APELA downregulated in asthma, both significantly correlated with various immune cells. A diagnostic model based on these genes demonstrated high predictive accuracy. Additionally, KU-55933 was identified as a potential small-molecule inhibitor of AGPS, with stable binding confirmed through computational simulations. These findings emphasize the role of ferroptosis-related genes in asthma and propose promising therapeutic candidates, providing novel insights into its diagnosis and treatment.

Authors

  • Yuhang Chen
    School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China,People's Republic of China.
  • Jie Wang
  • Ye Zhang
    Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • Ziwei Zhang
    College of Chemistry, Jilin University, Qianjin Street 2699, Changchun, Jilin, 130012, China. zzw@jlu.edu.cn.
  • Hong Chen
    Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • Jiaojiao Hu
    Department of Integrated Chinese and Western Medicine, Xi'an Children's Hospital, Xi'an, 710003, China.
  • Ke Zhu
    Kaifeng Eye Hospital, Kaifeng, China.
  • Liqun Wu
  • Fangwei Xu
    Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China. 13071182105@163.com.

Keywords

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