A co-expression network based molecular characterization of genes responsive for Braak stages in Parkinson's disease

Abstract

The progression of Parkinson's disease (PD) is defined by six Braak stages. We used transcriptome data from PD patients with Braak stage information to understand underlying molecular mechanisms for the progress of the disease. We created networks of genes with continuously decreased/increased co-expression from control group to Braak 5-6 stages. These networks are significantly associated with PD-related mechanisms such as mitochondrial dysfunction and synaptic signalling among others. Applying weighted gene co-expression network analysis (WGCNA) algorithm to the co-expression networks led to more specific modules enriched with neurodegeneration-related disease pathways, seizure, abnormality of coordination, and hypotonia. Furthermore, we showed that one of the co-expression networks is clustered into three major communities with dedicated molecular functions: (i) tubulin folding pathway, gap junction-related mechanisms, neuronal system; (ii) synaptic vesicle, intracellular vesicle, proteasome complex, PD genes; (iii) energy metabolism, mitochondrial mechanisms, oxidative phosphorylation, TCA cycle, PD genes. The co-expression relations we identified in this study as crucial players in the disease progression cover several known PD-associated genes and genes whose products are known to physically interact with alpha-synuclein protein.