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Updated: May 9, 2025

A Knowledge Graph Approach to Elucidate the Role of Organellar Pathways in Disease via Biomedical Reports
Published on: October 13, 2023
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.
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.
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.
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