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

George D Vavougios; Sotirios G Zarogiannis; Karen A Krogfelt; George Stamoulis; Konstantinos I Gourgoulianis

doi:10.1016/j.tube.2020.101938

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

Tuberculosis (Edinb). 2020 Jul:123:101938. doi: 10.1016/j.tube.2020.101938. Epub 2020 May 31.

Authors

George D Vavougios¹, Sotirios G Zarogiannis², Karen A Krogfelt³, George Stamoulis⁴, Konstantinos I Gourgoulianis⁵

Affiliations

¹ Department of Neurology, Athens Naval Hospital, Deinokratous 70, 115 21, Athens, Greece; Department of Electrical and Computer Engineering, 37 Glavani - 28th October Street, Deligiorgi Building, 4th floor, 382 21, Volos, Greece. Electronic address: dantevavougios@hotmail.com.
² Department of Pleural Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Mezourlo, 41500, Larisa, Greece.
³ Department of Science and Environment, Molecular and Medical Biology, Roskilde University, Universitetsvej 1, 28A.1, DK-4000, Roskilde, Denmark.
⁴ Department of Electrical and Computer Engineering, 37 Glavani - 28th October Street, Deligiorgi Building, 4th floor, 382 21, Volos, Greece.
⁵ Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Mezourlo, 41110, Larisa, Greece.

PMID: 32741527
DOI: 10.1016/j.tube.2020.101938

Abstract

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.

Keywords: Mycobacteria; Parkinson's; Pathway; Systems; Tuberculosis; biology; d; enrichment; isease.

MeSH terms

Apoptosis*
Case-Control Studies
Cross-Sectional Studies
Databases, Genetic
Epigenesis, Genetic*
Gene Expression Profiling
Gene Regulatory Networks
Host-Pathogen Interactions
Humans
Leukocytes, Mononuclear / enzymology*
Leukocytes, Mononuclear / microbiology
Leukocytes, Mononuclear / pathology
Longitudinal Studies
Mycobacterium tuberculosis / pathogenicity*
Protein Deglycase DJ-1 / genetics*
Protein Deglycase DJ-1 / metabolism
Protein Interaction Maps
Signal Transduction
Systems Biology*
Transcription, Genetic
Transcriptome
Tuberculosis / blood
Tuberculosis / enzymology*
Tuberculosis / genetics
Tuberculosis / microbiology

Substances

PARK7 protein, human
Protein Deglycase DJ-1