Machine learning analysis of gene expression profiles of pyroptosis-related differentially expressed genes in ischemic stroke revealed potential targets for drug repurposing.

Journal: Scientific reports
PMID:

Abstract

The relationship between ischemic stroke (IS) and pyroptosis centers on the inflammatory response elicited by cerebral tissue damage during an ischemic stroke event. However, an in-depth mechanistic understanding of their connection remains limited. This study aims to comprehensively analyze the gene expression patterns of pyroptosis-related differentially expressed genes (PRDEGs) by employing integrated IS datasets and machine learning techniques. The primary objective was to develop classification models to identify crucial PRDEGs integral to the ischemic stroke process. Leveraging three distinct machine learning algorithms (LASSO, Random Forest, and Support Vector Machine), models were developed to differentiate between the Control and the IS patient samples. Through this approach, a core set of 10 PRDEGs consistently emerged as significant across all three machine learning models. Subsequent analysis of these genes yielded significant insights into their functional relevance and potential therapeutic approaches. In conclusion, this investigation underscores the pivotal role of pyroptosis pathways in ischemic stroke and identifies pertinent targets for therapeutic development and drug repurposing.

Authors

  • Changchun Hei
    Key Laboratory for Craniocerebral Diseases of Ningxia Hui Autonomous Region, Department of Human Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan, China.
  • Xiaowen Li
    State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • Ruochen Wang
    Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, China.
  • Jiahui Peng
    Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, China.
  • Ping Liu
    Department of Cardiology, the Second Hospital of Shandong University, 250033 Jinan, Shandong, China.
  • Xialan Dong
    Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Technology Enterprise (BRITE), College of Health and Sciences, North Carolina Central University, Durham, NC, USA.
  • P Andy Li
    Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Technology Enterprise (BRITE), College of Health and Sciences, North Carolina Central University, Durham, NC, USA.
  • Weifan Zheng
    Biomanufacturing Research Institute and Technology Enterprise (BRITE), NCCU, Durham, NC 27707, United States.
  • Jianguo Niu
    Key Laboratory for Craniocerebral Diseases of Ningxia Hui Autonomous Region, Department of Human Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan, China. niujg@nxmu.edu.cn.
  • Xiao Yang
    Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.