Gene Prioritization in Parkinson's Disease Using Human Protein–Protein Interaction Network

Abstract

Parkinson's disease (PD) is the second-most common neurodegenerative disorder, and the actual cause of this disease is still unknown. Identifying the target genes that are associated with disease plays an essential role in the treatment of PD. Various genetic studies have determined the significant target genes for disease progression, although this continues to be challenging in the field of drug designing. In this study, we proposed a network-based approach to identify target genes for PD using gene mutation, gene expression, and gene deletion analysis. The subnetwork of PD genes was constructed from human protein–protein interaction network, and the potential genes were identified using network centrality measures. Two genes, PARK1 and PARK2, were identified as target genes by integrating gene mutation and expression data into the subnetwork. Gene deletion analysis was carried out to determine the significant target, and results revealed that VDAC1 and ATP5C1 genes were crucial for the Parkinson's subnetwork. Thus, findings from the network-based approach will provide additional insight for understanding the disease mechanism of PD. Future enhancement of this study may help in predicting disease biomarkers as well as designing novel compounds in rational drug designing.