Severity of COVID-19 patients with coexistence of asthma and vitamin D deficiency.

Coronavirus disease 2019 (COVID-19)-driven global pandemic triggered innumerable health complications, imposing great challenges in managing other respiratory diseases like asthma. Furthermore, increases in the underlying inflammation involved in the fatality of COVID-19 have been linked with lack of vitamin D. In this research work, we intend to investigate the possible genetic linkage of asthma and vitamin D deficiency with the severity and fatality of COVID-19 using a network-based approach. We identified and analysed 41 and 14 differentially expressed genes (DEGs) of COVID-19 being common with asthma and vitamin D deficiency, respectively, through the comparative differential gene expression analysis and their footprints on signalling pathways. Gene set enrichment analysis for GO terms and signalling pathways reveals key biological activities, including inflammatory response-related pathways (e.g., cytokine- and chemokine-mediated signalling pathways, IL-17, and TNF signalling pathways). Besides, the Protein-Protein Interaction network analysis of those DEGs reveals hub proteins, some of which are reported as inflammatory antiviral interferon-stimulated biomarkers that potentially drive the cytokine storm leading to COVID-19 severity and fatality, and contributes in the early stage of viral replication, respectively. Moreover, the regulatory network analysis found these DEGs associated with antiviral and tumour inhibitory transcription factors and micro-RNAs. Finally, drug-target enrichment analysis yields tetradioxin, estradiol, arsenenous acid, and zinc, which have been reported to be effective in suppressing the pro-inflammatory cytokines production, and other respiratory tract infections. Our results yield shared biomarker-driven key hypotheses followed by network-based analytics, demystifying the mechanistic details of COVID-19 comorbidity of asthma and vitamin D deficiency with their potential therapeutic implications.

Bioinformatics and System Biological Approaches for the Identification of Genetic Risk Factors in the Progression of Cardiovascular Disease.

Background: Cardiovascular disease (CVD) is the combination of coronary heart disease, myocardial infarction, rheumatic heart disease, and peripheral vascular disease of the heart and blood vessels. It is one of the leading deadly diseases that causes one-third of the deaths yearly in the globe. Additionally, the risk factors associated with it make the situation more complex for cardiovascular patients, which lead them towards mortality, but the genetic association between CVD and its risk factors is not clearly explored in the global literature. We addressed this issue and explored the linkage between CVD and its risk factors. Methods: We developed an analytical approach to reveal the risk factors and their linkages with CVD. We used GEO microarray datasets for the CVD and other risk factors in this study. We performed several analyses including gene expression analysis, diseasome analysis, protein-protein interaction (PPI) analysis, and pathway analysis for discovering the relationship between CVD and its risk factors. We also examined the validation of our study using gold benchmark databases OMIM, dbGAP, and DisGeNET. Results: We observed that the number of 32, 17, 53, 70, and 89 differentially expressed genes (DEGs) is overlapped between CVD and its risk factors of hypertension (HTN), type 2 diabetes (T2D), hypercholesterolemia (HCL), obesity, and aging, respectively. We identified 10 major hub proteins (FPR2, TNF, CXCL8, CXCL1, IL1B, VEGFA, CYBB, PTGS2, ITGAX, and CCR5), 12 significant functional pathways, and 11 gene ontological pathways that are associated with CVD. We also found the connection of CVD with its risk factors in the gold benchmark databases. Our experimental outcomes indicate a strong association of CVD with its risk factors of HTN, T2D, HCL, obesity, and aging. Conclusions: Our computational approach explored the genetic association of CVD with its risk factors by identifying the significant DEGs, hub proteins, and signaling and ontological pathways. The outcomes of this study may be further used in the lab-based analysis for developing the effective treatment strategies of CVD.

Effects of Bacille Calmette Guerin (BCG) vaccination during COVID-19 infection.

The coronavirus disease 2019 (COVID-19) is caused by the infection of highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as the novel coronavirus. In most countries, the containment of this virus spread is not controlled, which is driving the pandemic towards a more difficult phase. In this study, we investigated the impact of the Bacille Calmette Guerin (BCG) vaccination on the severity and mortality of COVID-19 by performing transcriptomic analyses of SARS-CoV-2 infected and BCG vaccinated samples in peripheral blood mononuclear cells (PBMC). A set of common differentially expressed genes (DEGs) were identified and seeded into their functional enrichment analyses via Gene Ontology (GO)-based functional terms and pre-annotated molecular pathways databases, and their Protein-Protein Interaction (PPI) network analysis. We further analysed the regulatory elements, possible comorbidities and putative drug candidates for COVID-19 patients who have not been BCG-vaccinated. Differential expression analyses of both BCG-vaccinated and COVID-19 infected samples identified 62 shared DEGs indicating their discordant expression pattern in their respected conditions compared to control. Next, PPI analysis of those DEGs revealed 10 hub genes, namely ITGB2, CXCL8, CXCL1, CCR2, IFNG, CCL4, PTGS2, ADORA3, TLR5 and CD33. Functional enrichment analyses found significantly enriched pathways/GO terms including cytokine activities, lysosome, IL-17 signalling pathway, TNF-signalling pathways. Moreover, a set of identified TFs, miRNAs and potential drug molecules were further investigated to assess their biological involvements in COVID-19 and their therapeutic possibilities. Findings showed significant genetic interactions between BCG vaccination and SARS-CoV-2 infection, suggesting an interesting prospect of the BCG vaccine in relation to the COVID-19 pandemic. We hope it may potentially trigger further research on this critical phenomenon to combat COVID-19 spread.

Identifying molecular insight of synergistic complexities for SARS-CoV-2 infection with pre-existing type 2 diabetes.

The ongoing COVID-19 outbreak, caused by SARS-CoV-2, has posed a massive threat to global public health, especially to people with underlying health conditions. Type 2 diabetes (T2D) is lethal comorbidity of COVID-19. However, its pathogenetic link remains unclear. This research aims to determine the genetic factors and processes contributing to the synergistic severity of SARS-CoV-2 infection among T2D patients through bioinformatics approaches. We analyzed two sets of transcriptomic data of SARS-CoV-2 infection obtained from lung epithelium cells and PBMCs, and two sets of T2D data from pancreatic islet cells and PBMCs to identify the associated differentially expressed genes (DEGs) followed by their functional enrichment analyses in terms of protein-protein interaction (PPI) to detect hub-proteins and associated comorbidities, transcription factors (TFs), microRNAs (miRNAs) as well as the potential drug candidates. In PPI analysis, four potential hub-proteins (i.e., BIRC3, C3, MME, and IL1B) were identified among 25 DEGs shared between the disease pair. Enrichment analyses using the mutually overlapped DEGs revealed the most prevalent GO and cell signalling pathways, including TNF signalling, cytokine-cytokine receptor interaction, and IL-17 signalling, which are related to cytokine activities. Furthermore, as significant TFs, we identified IRF1, KLF11, FOSL1, and CREB3L1 while miRNAs including miR-1-3p, 34a-5p, 16-5p, 155-5p, 20a-5p, and let-7b-5p were found to be noteworthy. The findings illustrated the significant association between COVID-19 and T2D at the molecular level. These genetic determinants can further be explored for their specific roles in disease progression and therapeutic intervention, while significant pathways can also be studied as molecular checkpoints. Finally, the identified drug candidates may be evaluated for their potency to minimize the severity of COVID-19 patients with pre-existing T2D.

Machine learning and network-based models to identify genetic risk factors to the progression and survival of colorectal cancer.

Colorectal cancer (CRC) is one of the most common and lethal malignant lesions. Determining how the identified risk factors drive the formation and development of CRC could be an essential means for effective therapeutic development. Aiming this, we investigated how the altered gene expression resulting from exposure to putative CRC risk factors contribute to prognostic biomarker identification. Differentially expressed genes (DEGs) were first identified for CRC and other eight risk factors. Gene set enrichment analysis (GSEA) through the molecular pathway and gene ontology (GO), as well as protein-protein interaction (PPI) network, were then conducted to predict the functions of these DEGs. Our identified genes were explored through the dbGaP and OMIM databases to compare with the already identified and known prognostic CRC biomarkers. The survival time of CRC patients was also examined using a Cox Proportional Hazard regression-based prognostic model by integrating transcriptome data from The Cancer Genome Atlas (TCGA). In this study, PPI analysis identified 4 sub-networks and 8 hub genes that may be potential therapeutic targets, including CXCL8, ICAM1, SOD2, CXCL2, CCL20, OIP5, BUB1, ASPM and IL1RN. We also identified seven signature genes (PRR5.ARHGAP8, CA7, NEDD4L, GFR2, ARHGAP8, SMTN, OIP5) in independent analysis and among which PRR5. ARHGAP8 was found in both multivariate analyses and in analyses that combined gene expression and clinical information. This approach provides both mechanistic information and, when combined with predictive clinical information, good evidence that the identified genes are significant biomarkers of processes involved in CRC progression and survival.

System biology and bioinformatics pipeline to identify comorbidities risk association: Neurodegenerative disorder case study.

Alzheimer's disease (AD) is the commonest progressive neurodegenerative condition in humans, and is currently incurable. A wide spectrum of comorbidities, including other neurodegenerative diseases, are frequently associated with AD. How AD interacts with those comorbidities can be examined by analysing gene expression patterns in affected tissues using bioinformatics tools. We surveyed public data repositories for available gene expression data on tissue from AD subjects and from people affected by neurodegenerative diseases that are often found as comorbidities with AD. We then utilized large set of gene expression data, cell-related data and other public resources through an analytical process to identify functional disease links. This process incorporated gene set enrichment analysis and utilized semantic similarity to give proximity measures. We identified genes with abnormal expressions that were common to AD and its comorbidities, as well as shared gene ontology terms and molecular pathways. Our methodological pipeline was implemented in the R platform as an open-source package and available at the following link: https://github.com/unchowdhury/AD_comorbidity. The pipeline was thus able to identify factors and pathways that may constitute functional links between AD and these common comorbidities by which they affect each others development and progression. This pipeline can also be useful to identify key pathological factors and therapeutic targets for other diseases and disease interactions.

Network-based computational approach to identify genetic links between cardiomyopathy and its risk factors.

Cardiomyopathy (CMP) is a group of myocardial diseases that progressively impair cardiac function. The mechanisms underlying CMP development are poorly understood, but lifestyle factors are clearly implicated as risk factors. This study aimed to identify molecular biomarkers involved in inflammatory CMP development and progression using a systems biology approach. The authors analysed microarray gene expression datasets from CMP and tissues affected by risk factors including smoking, ageing factors, high body fat, clinical depression status, insulin resistance, high dietary red meat intake, chronic alcohol consumption, obesity, high-calorie diet and high-fat diet. The authors identified differentially expressed genes (DEGs) from each dataset and compared those from CMP and risk factor datasets to identify common DEGs. Gene set enrichment analyses identified metabolic and signalling pathways, including MAPK, RAS signalling and cardiomyopathy pathways. Protein-protein interaction (PPI) network analysis identified protein subnetworks and ten hub proteins (CDK2, ATM, CDT1, NCOR2, HIST1H4A, HIST1H4B, HIST1H4C, HIST1H4D, HIST1H4E and HIST1H4L). Five transcription factors (FOXC1, GATA2, FOXL1, YY1, CREB1) and five miRNAs were also identified in CMP. Thus the authors' approach reveals candidate biomarkers that may enhance understanding of mechanisms underlying CMP and their link to risk factors. Such biomarkers may also be useful to develop new therapeutics for CMP.