Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

Abstract

People with diabetes are more likely to have severe COVID-19 compared to the general population. Moreover, diabetes and COVID-19 demonstrate a certain parallelism in the mechanisms and organ damage. In this work, we applied bioinformatics analysis of associative molecular networks to identify key molecules and pathophysiological processes that determine SARS-CoV-2-induced disorders in patients with diabetes. Using text-mining-based approaches and ANDSystem as a bioinformatics tool, we reconstructed and matched networks related to hyperglycemia, diabetic complications, insulin resistance, and beta cell dysfunction with networks of SARS-CoV-2-targeted proteins. The latter included SARS-CoV-2 entry receptors (ACE2 and DPP4), SARS-CoV-2 entry associated proteases (TMPRSS2, CTSB, and CTSL), and 332 human intracellular proteins interacting with SARS-CoV-2. A number of genes/proteins targeted by SARS-CoV-2 (ACE2, BRD2, COMT, CTSB, CTSL, DNMT1, DPP4, ERP44, F2RL1, GDF15, GPX1, HDAC2, HMOX1, HYOU1, IDE, LOX, NUTF2, PCNT, PLAT, RAB10, RHOA, SCARB1, and SELENOS) were found in the networks of vascular diabetic complications and insulin resistance. According to the Gene Ontology enrichment analysis, the defined molecules are involved in the response to hypoxia, reactive oxygen species metabolism, immune and inflammatory response, regulation of angiogenesis, platelet degranulation, and other processes. The results expand the understanding of the molecular basis of diabetes and COVID-19 comorbidity.

The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients

“…In ARDS due to other causes, higher ang-2 has been linked to the underlying pathogenesis of ARDS 31 . Ang-2 is normally downregulated by angiotensin-converting enzyme 2 (ACE2) 32 . Given that ACE2 is a receptor for SARS-CoV-2 entry in the host cells, leading to downregulation of ACE2 with ensuing endothelial dysfunction 33 , the ratio of ang-2/ang-1 is of particular relevance in COVID-19 induced ARDS.…”

Exploring the shared gene signatures of smoking-related osteoporosis and chronic obstructive pulmonary disease using machine learning algorithms

“…Using gene network analysis, a prior study identified PLAT as a SARS-CoV-2 target and elucidated its potential involvement in COVID-19's inflammatory response, metabolism of reactive oxygen species, and immune response. (Saik and Klimontov, 2022). Wan et al conducted a large-scale genome-wide analysis of two COPD cohorts and obtained DNA methylation data for 27,578 CpG sites in 14,475 genes.…”

Medical Genetics, Genomics and Bioinformatics—2022

“…Studying genetic variants in populations is an important approach applied earlier for diabetes [21]. Olga Saik and Vadim Klimontov [22] considered the challenging problem of COVID-19 complications and comorbidity including diabetes. Using text-mining-based approaches and the ANDSystem [23,24] as a bioinformatics tool, the authors reconstructed and matched networks related to hyperglycemia, diabetic complications, insulin resistance and beta cell dysfunction with networks of SARS-CoV-2-targeted proteins.…”