Protein interactions, network pharmacology, and machine learning work together to predict genes linked to

Jia-Lin Chen1,2, Di Xiao1, Yi-Jiang Liu1

  • 1The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, NO.55, Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.

Scientific Reports
|April 29, 2025
PubMed

Insights

Researchers identified CCAAT/Enhancer Binding Protein Delta (CEBPD) as a key gene target for hypertrophic cardiomyopathy (HCM). Lower CEBPD levels in HCM models suggest it could be a therapeutic target, with Abt-751 showing potential as a drug candidate.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Genetics

Background:

  • Hypertrophic cardiomyopathy (HCM) is characterized by ventricular wall thickening, impacting cardiac function.
  • Identifying novel therapeutic targets is crucial for managing HCM.
  • Understanding the molecular mechanisms underlying HCM is essential for developing effective treatments.

Purpose of the Study:

  • To identify novel molecular targets for hypertrophic cardiomyopathy (HCM).
  • To investigate the role of CCAAT/Enhancer Binding Protein Delta (CEBPD) in HCM.
  • To explore potential therapeutic strategies and drug candidates for HCM.

Main Methods:

  • Differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA).
  • Machine learning techniques and protein-protein interaction (PPI) network analysis to identify the most characteristic gene (MCG).
  • Validation of MCG expression in HCM models and molecular docking for drug prediction.

Main Results:

  • Identified 7975 differentially expressed genes (DEGs) and 236 genes in the WGCNA blue module.
  • Screened and validated CCAAT/Enhancer Binding Protein Delta (CEBPD) as the MCG for HCM.
  • Observed reduced CEBPD mRNA and protein levels in HCM animal and cell models; Abt-751 showed high binding affinity to CEBPD.

Conclusions:

  • CEBPD is a novel potential therapeutic target for HCM, likely through mechanisms involving mitochondrial dysfunction.
  • Reduced CEBPD expression in HCM suggests its protective role, making it a target for therapeutic intervention.
  • Abt-751 is a potential drug candidate for HCM treatment, warranting further investigation due to its binding affinity with CEBPD.

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