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

Aims: The aims of our study were a. to determine for the first time differentially expressed genes (DEGs) and enriched biological processes from the PARK7 interactome, in PBMCs donated from active and latent tuberculosis patients and b. to assess a treatment effect, via a systems biology approach.

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 DAVID and GENEmania algorithms.

Results: 21 DEGs were identified from the PARK7 interactome: TALDO1, PRDX5, BAX, PTEN, OTUD7B, STUB1, PARK7, TDP2, MAP3K5, SNCA, NDUFA4, BABAM1, RBBP4, NONO, HDAC2, CASP8, HTRA2, PIAS2, SUMO1, MTRF1, TP53. The Gene Ontology Terms “Acetylation”, “Ubiquitin Like (UBL) Conjugation” and “Promyelocytic leukemia nuclear Bodies (PML-NB)” were determined as significantly enriched (P<0.05) for the Case-Control Study; conversely, 22 DEGS and positive regulation of apoptosis via mitochondrial signaling were the predominant GO annotations in the treatment dataset.

Conclusions: Our in silico analysis reveals for the first time the role of PARK7's interactome in regulating the PBMC lifecycle in tuberculosis via the PARK7 interactome; This network is unique when compared to autoimmune inflammation (Vavougios et al, 2017) and promotes apoptosis via mitochondrial signaling in response to anti-TB treatment. Our results are in line with the emerging role of PARK7 as a regulator of immunity.