Epigenetic regulation of apoptosis via the PARK7 interactome in peripheral blood mononuclear cells donated by tuberculosis patients vs. healthy controls and the response to treatment: A systems biology approach

Aims: The aims of our study were to determine for the first time differentially expressed genes (DEGs) and enriched molecular pathways involving the PARK7 interactome in PBMCs donated from tuberculosis patients. Methods: Data on a previously reconstructed PARK7 interactome (Vavougios et al., 2017) from datasets GDS4966 (Case-Control) and GDS4781 (Treatment Series) were retrieved from the Gene Expression Omnibus (GEO) repository. Gene Enrichment analysis was performed via the STRING algorithm and the GeneTrail2 software. Results: 17 and 22 PARK7 interactores were determined as DEGs in the active TB vs HD and Treatment Series subset analyses, correspondingly, associated with significantly enriched pathways (FDR <0.05) involving p53 and PTEN mediated, stress responsive apoptosis regulation pathways. The treatment subset was characterized by the emergence of an additional layer of transcriptional regulation mediated by polycomb proteins among others, as well as TLR-mediated and cytokine survival signaling. Finally, the enrichment of a Parkinson's disease signature including PARK7 interactors was determined by its differential regulation both in the exploratory analyses (FDR = 0.024), as well as the confirmatory analyses (FDR = 1.81e-243). Conclusions: Our in silico analysis revealed for the first time the role of PARK7's interactome in regulating the epigenetics of the PBMC lifecycle and Mtb symbiosis.