Bioinformatics and next generation sequencing data analysis to identify key genes and pathways influencing in Parkinson’s disease

Abstract

Parkinson's disease (PD) is the most commonly diagnosed neurodegenerative disorder Identification of novel prognostic and pathogenesis biomarkers plays a pivotal role in the management of the PD. Next generation sequencing (NGS) dataset from the GEO (Gene Expression Omnibus) database were used to identify differentially expressed genes (DEGs) in PD. Gene Ontology (GO) and REACTOME pathway enrichmental analyses were performed to elucidate the functional roles of the DEGs. Protein-protein interaction (PPI), modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were established. The receiver operating characteristic curve (ROC) analysis was used to explore the diagnostic values of hub genes in PD. In total, 957 DEGs were identified, of which 478 were up regulated genes and 479 were down regulated genes. GO and pathway enrichment analysis results revealed that the up regulated genes were mainly enriched in nervous system development, cell junction, transporter activity and neuronal system, whereas down regulated genes were mainly enriched in response to stimulus, cell periphery, identical protein binding and immune system. The top hub genes in the constructed PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were OTUB1, PPP2R1A, AP2M1, PIN1, USP11, CDK2, IQGAP1, NEDD4, VIM and CDK1. Furthermore, ROC analysis showed that hub genes were having good diagnostic values. We identified a series of essential genes along with the pathways that were most closely related with PD initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of PD, shedding light on the potential biomarkers and therapeutic targets.