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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Utilizing bioinformatics and machine learning to identify CXCR4 gene-related therapeutic targets in diabetic foot
Hengyan Zhang1, Ye Zhou2, Heguo Yan2
1Department of Dermatology, Zhaotong Hospital of Traditional Chinese Medicine, Zhaotong, Yunnan, China.
Background:
Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus that manifests as chronic, non-healing wounds that have a significant impact on patients quality of life. Identifying key molecular targets associated with DFUs could help develop targeted therapies to promote wound healing and prevent further complications. The CXCR4 gene is known to play a key role in cell migration, immunology response, and tissue repair, and thus may be an important target for DFU treatment.
Methods:
We used the GEO database (Gene Expression Omnibus database) to obtain DFU-related gene expression data, identified differentially expressed genes (DEGs), and performed enrichment analysis to reveal the related biological pathways. Meanwhile, protein-protein interaction (PPI) networks were constructed using STRING to identify core genes. Feature selection methods such as LASSO, SVM-RFE and random forest algorithm were applied to localize possible therapeutic target genes. Finally, We analyzed the molecular pathways of CXCR4 in DFUs by Gene set enrichment analysis (GSEA).
Results:
We identified a total of 751 differential genes, of which 409 genes were significantly upregulated and 342 genes were downregulated in diabetic foot ulcer tissues. Functional enrichment analysis showed that these genes were mainly involved in pathways such as oxidative phosphorylation, phagosome, synaptic vesicle cycle, and pathways of neurodegeneration. We integrated the genes screened by three machine learning models (LASSO, SVM, and Random Forest), and CXCR4 was identified as a key gene with potential therapeutic value in DFUs. Gene set enrichment analysis (GSEA) showed that CXCR4 was closely associated with pathways related to immunology regulation and tissue repair.
Conclusion:
The findings suggest that CXCR4 and its related pathways play an important role in the pathogenesis of DFUs, providing a new perspective on targeted therapy for wound healing in diabetic patients. Further validation of the role of CXCR4 is expected to establish it as an important target in DFU management.
Insights
CXCR4 is a key gene in diabetic foot ulcers (DFUs), impacting wound healing. Targeting CXCR4 offers a new therapeutic approach for DFU treatment and improved patient outcomes.
Area of Science:
- Molecular biology
- Genomics
- Diabetes research
Background:
- Diabetic foot ulcers (DFUs) are chronic, non-healing wounds significantly impacting diabetes mellitus patients' quality of life.
- Identifying molecular targets is crucial for developing effective DFU therapies.
- The CXCR4 gene is implicated in cell migration, immune response, and tissue repair, suggesting its potential role in DFU pathogenesis.
Purpose of the Study:
- To identify key molecular targets for DFU treatment.
- To investigate the role of CXCR4 in the pathogenesis of diabetic foot ulcers.
- To explore CXCR4 as a potential therapeutic target for promoting DFU wound healing.
Main Methods:
- Utilized the Gene Expression Omnibus (GEO) database to obtain DFU gene expression data.
- Identified differentially expressed genes (DEGs) and performed enrichment analysis.
- Employed machine learning models (LASSO, SVM-RFE, Random Forest) and protein-protein interaction networks to identify core therapeutic target genes, including CXCR4.
- Conducted Gene Set Enrichment Analysis (GSEA) to analyze CXCR4's molecular pathways in DFUs.
Main Results:
- Identified 751 differentially expressed genes in DFU tissues, with 409 upregulated and 342 downregulated.
- Functional enrichment analysis revealed involvement in pathways like oxidative phosphorylation and neurodegeneration.
- CXCR4 was identified as a key gene with therapeutic potential through integrated machine learning models.
- GSEA indicated CXCR4's association with immunology regulation and tissue repair pathways.
Conclusions:
- CXCR4 and its associated pathways are integral to DFU pathogenesis.
- Targeting CXCR4 presents a novel therapeutic strategy for DFU wound healing in diabetic patients.
- Further validation of CXCR4's role is essential for its clinical application in DFU management.
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