Novel candidate genes of the PARK7 interactome as mediators of apoptosis and acetylation in multiple sclerosis: An in silico analysis

Background: currently only 4 studies have explored the potential role of PARK7's dysregulation in MS pathophysiology Currently, no study has evaluated the potential role of the PARK7 interactome in MS. Objective: The aim of our study was to assess the differential expression of PARK7 mRNA in peripheral blood mononuclears (PBMCs) donated from MS versus healthy patients using data mining techniques. Methods: The PARK7 interactome data from the GDS3920 profile were scrutinized for differentially expressed genes (DEGs); Gene Enrichment Analysis (GEA) was used to detect significantly enriched biological functions. Results: 27 differentially expressed genes in the MS dataset were detected; 12 of these (NDUFA4, UBA2, TDP2, NPM1, NDUFS3, SUMO1, PIAS2, KIAA0101, RBBP4, NONO, RBBP7 AND HSPA4) are reported for the first time in MS. Stepwise Linear Discriminant Function Analysis constructed a predictive model (Wilk's lambda= 0.176, chi(2) = 45.204, p = 1.5275e(-10)) with 2 variables (TIDP2, RBBP4) that achieved 96.6% accuracy when discriminating between patients and controls. Gene Enrichment Analysis revealed that induction and regulation of programmed / intrinsic cell death represented the most salient Gene Ontology annotations. Cross-validation on systemic lupus erythematosus and ischemic stroke datasets revealed that these functions are unique to the MS dataset. Conclusions: Based on our results, novel potential target genes are revealed; these differentially expressed genes regulate epigenetic and apoptotic pathways that may further elucidate underlying mechanisms of autorreactivity in MS.