Transcriptome and machine learning analysis of the impact of COVID-19 on mitochondria and multiorgan damage

PLoS One. 2024 Jan 31;19(1):e0297664. doi: 10.1371/journal.pone.0297664. eCollection 2024.

Abstract

The effects of coronavirus disease 2019 (COVID-19) primarily concern the respiratory tract and lungs; however, studies have shown that all organs are susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may involve multiorgan damage from direct viral invasion through angiotensin-converting enzyme 2 (ACE2), through inflammatory cytokine storms, or through other secondary pathways. This study involved the analysis of publicly accessible transcriptome data from the Gene Expression Omnibus (GEO) database for identifying significant differentially expressed genes related to COVID-19 and an investigation relating to the pathways associated with mitochondrial, cardiac, hepatic, and renal toxicity in COVID-19. Significant differentially expressed genes were identified and ranked by statistical approaches, and the genes derived by biological meaning were ranked by feature importance; both were utilized as machine learning features for verification. Sample set selection for machine learning was based on the performance, sample size, imbalanced data state, and overfitting assessment. Machine learning served as a verification tool by facilitating the testing of biological hypotheses by incorporating gene list adjustment. A subsequent in-depth study for gene and pathway network analysis was conducted to explore whether COVID-19 is associated with cardiac, hepatic, and renal impairments via mitochondrial infection. The analysis showed that potential cardiac, hepatic, and renal impairments in COVID-19 are associated with ACE2, inflammatory cytokine storms, and mitochondrial pathways, suggesting potential medical interventions for COVID-19-induced multiorgan damage.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • COVID-19* / genetics
  • Cytokine Release Syndrome
  • Humans
  • Peptidyl-Dipeptidase A / metabolism
  • SARS-CoV-2 / genetics
  • Transcriptome

Substances

  • Angiotensin-Converting Enzyme 2
  • Peptidyl-Dipeptidase A

Grants and funding

This work was supported by the Center for Advanced Computing and Imaging in Biomedicine (NTU-112L900701) from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.