Protein interactions, network pharmacology, and machine learning work together to predict genes linked to mitochondrial dysfunction in hypertrophic cardiomyopathy.

Journal: Scientific reports
PMID:

Abstract

This study looked at possible targets for hypertrophic cardiomyopathy (HCM), a condition marked by thickening of the ventricular wall, primarily in the left ventricle. We employed differential gene analysis and weighted gene co-expression network analysis (WGCNA) on samples. We then carried out an enrichment analysis. We also investigated the process of immunological infiltration. We employed six machine learning techniques and two protein-protein interaction (PPI) network gene selection approaches to search for the most characteristic gene (MCG). In the validation ladder, we verified the expression of MCG. Furthermore, we examined the MCG expression levels in HCM animal and cell models. Finally, we performed molecular docking and predicted potential medications for HCM treatment. 7975 differentially expressed genes (DEGs) were found in our study. We also identified 236 genes in the blue module using WGCNA. Screening at the transcriptome and protein levels was used to mine MCG. The final result screened CCAAT/Enhancer Binding Protein Delta (CEBPD) as MCG. We confirmed that MCG expression matched the outcomes of the experimental ladder. The level of CEBPD mRNA and protein was lowered in HCM animal and cellular models. Given that Abt-751 had the highest binding affinity to CEBPD, it might be a projected targeted medication. We found a new target gene for HCM called CEBPD, which is probably going to function by mitochondrial dysfunction. An innovative aim for the management or avoidance of HCM is offered by this analysis. Abt-751 may be a predicted targeted drug for HCM that had the greatest binding affinity with CEBPD.

Authors

  • Jia-Lin Chen
    The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.
  • Di Xiao
    Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Perth, Western Australia, Australia.
  • Yi-Jiang Liu
    The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.
  • Zhan Wang
    Interdisciplinary Research Center of Smart Sensor, Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China.
  • Zhi-Huang Chen
    The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.
  • Rui Li
    Department of Oncology, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, China.
  • Li Li
    Department of Gastric Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
  • Rong-Hai He
    Department of Cardiac Surgery, Xiangan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361100, Fujian, China.
  • Shu-Yan Jiang
    The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.
  • Xin Chen
    University of Nottingham, Nottingham, United Kingdom.
  • Lin-Xi Xu
    The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.
  • Feng-Chun Lu
    Department of General Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, China. fengchun160@fjmu.edu.cn.
  • Jia-Mao Wang
    The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China. 635442665@qq.com.
  • Zhong-Gui Shan
    The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China. szgdoctor@126.com.