Identification of Significant Immune Related Genes and Pathways in Parkinson’s disease via Bioinformatics Analysis of Single-Cell RNA Sequencing Data
Identification of Significant Immune Related Genes and Pathways in Parkinson’s disease via Bioinformatics Analysis of Single-Cell RNA Sequencing Data
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Original abstract
Abstract Parkinson’s disease (PD) is a neurodegenerative disorder that is predominantly mediated by inflammation and immunity. The aim of this study was to identify key biomarkers of PD and investigate their association with immune-related mechanisms, inflammatory cytokines, chemokines and chemokine receptors (CCRs). PD single-cell RNA sequencing expression data (GSE223138) was downloaded from the GEO database. Differentially expressed gene (DEG) analysis was performed using Seurat. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the DEGs. Protein-protein interaction network and its modules were derived using the Human Integrated Protein-Protein Interaction rEference (HIPPIE) database and visualized using Cytoscape software. Potential biomarker genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). Finally, a miRNA-hub gene regulatory network, TF-hub gene regulatory network, and drug-hub gene interaction network were constructed. We identified 958 DEGs in the discovery phase, consisting of 479 up-regulated genes and 479 down-regulated genes. GO analysis verified that the DEGs were enriched in multicellular organismal process and response to stimulus. REACTOME analysis demonstrated that the DEGs were enriched in hemostasis and immune system. The PPI network analysis identified hub genes with high connectivity: HIST2H2BE, AR, PDGFRA, FHL2, SNCA, HSPD1, LRRK2, DISC1, MDM2 and KCNE3. Furthermore, miRNAs (hsa-miR-595 and hsa-miR-181c-3p) and TFs (POU2F2 and SOX9) revealed key regulatory networks influencing post-transcriptional gene regulation. Drug-hub gene interaction network predicted Mercaptoethanol and Linagliptin as promising therapeutic candidates for PD intervention. In conclusion, this study enhances our understanding of PD pathogenesis by identifying key biomarkers and therapeutic targets, paving the way for future advancements in personalized diagnosis and treatment strategies.