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Several studies have been done to identify comorbidities of COVID-19. In this work, we developed an analytical bioinformatics framework to reveal COVID-19 comorbidities, their genomic associations, and molecular mechanisms accomplishing transcriptomic analyses of the RNA-seq datasets provided by the Gene Expression Omnibus (GEO) database, where normal and infected tissues were evaluated. Using the framework, we identified 27 COVID-19 correlated diseases out of 7,092 collected diseases. Analyzing clinical and epidemiological research, we noticed that our identified 27 diseases are associated with COVID-19, where hypertension, diabetes, obesity, and lung cancer are observed several times in COVID-19 patients. Therefore, we selected the above four diseases and performed assorted analyses to demonstrate the association between COVID-19 and hypertension, diabetes, obesity, and lung cancer as comorbidities. We investigated genomic associations with the cross-comparative analysis and Jaccard’s similarity index, identifying shared differentially expressed genes (DEGs) and linking DEGs of COVID-19 and the comorbidities, in which we identified hypertension as the most associated illness. We also revealed molecular mechanisms by identifying statistically significant ten pathways and ten ontologies. Moreover, to understand cellular physiology, we did protein-protein interaction (PPI) analyses among the comorbidities and COVID-19. We also used the degree centrality method and identified ten biomarker hub proteins (IL1B, CXCL8, FN1, MMP9, CXCL10, IL1A, IRF7, VWF, CXCL9, and ISG15) that associate COVID-19 with the comorbidities. Finally, we validated our findings by searching the published literature. Thus, our analytical approach elicited interconnections between COVID-19 and the aforementioned comorbidities in terms of remarkable DEGs, pathways, ontologies, PPI, and biomarker hub proteins.

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.

The novel coronavirus (2019-nCoV) has recently emerged, causing COVID-19 outbreaks and significant societal/global disruption. Importantly, COVID-19 infection resembles SARS-like complications. However, the lack of knowledge about the underlying genetic mechanisms of COVID-19 warrants the development of prospective control measures. In this study, we employed whole-genome alignment and digital DNA–DNA hybridization analyses to assess genomic linkage between 2019-nCoV and other coronaviruses. To understand the pathogenetic behavior of 2019-nCoV, we compared gene expression datasets of viral infections closest to 2019-nCoV with four COVID-19 clinical presentations followed by functional enrichment of shared dysregulated genes. Potential chemical antagonists were also identified using protein–chemical interaction analysis. Based on phylogram analysis, the 2019-nCoV was found genetically closest to SARS-CoVs. In addition, we identified 562 upregulated and 738 downregulated genes (adj. P ≤ 0.05) with SARS-CoV infection. Among the dysregulated genes, SARS-CoV shared ≤19 upregulated and ≤22 downregulated genes with each of different COVID-19 complications. Notably, upregulation of BCL6 and PFKFB3 genes was common to SARS-CoV, pneumonia and severe acute respiratory syndrome, while they shared CRIP2, NSG1 and TNFRSF21 genes in downregulation. Besides, 14 genes were common to different SARS-CoV comorbidities that might influence COVID-19 disease. We also observed similarities in pathways that can lead to COVID-19 and SARS-CoV diseases. Finally, protein–chemical interactions suggest cyclosporine, resveratrol and quercetin as promising drug candidates against COVID-19 as well as other SARS-like viral infections. The pathogenetic analyses, along with identified biomarkers, signaling pathways and chemical antagonists, could prove useful for novel drug development in the fight against the current global 2019-nCoV pandemic.

BackgroundThe welding process releases potentially hazardous gases and fumes, mainly composed of metallic oxides, fluorides and silicates. Long term welding fume (WF) inhalation is a recognized health issue that carries a risk of developing chronic health problems, particularly respiratory system diseases (RSDs). Aside from general airway irritation, WF exposure may drive direct cellular responses in the respiratory system which increase risk of RSD, but these are not well understood.MethodsWe developed a quantitative framework to identify gene expression effects of WF exposure that may affect RSD development. We analyzed gene expression microarray data from WF-exposed tissues and RSD-affected tissues, including chronic bronchitis (CB), asthma (AS), pulmonary edema (PE), lung cancer (LC) datasets. We built disease-gene (diseasome) association networks and identified dysregulated signaling and ontological pathways, and protein-protein interaction sub-network using neighborhood-based benchmarking and multilayer network topology.ResultsWe observed many genes with altered expression in WF-exposed tissues were also among differentially expressed genes (DEGs) in RSD tissues; for CB, AS, PE and LC there were 34, 27, 50 and 26 genes respectively. DEG analysis, using disease association networks, pathways, ontological analysis and protein-protein interaction sub-network suggest significant links between WF exposure and the development of CB, AS, PE and LC.ConclusionsOur network-based analysis and investigation of the genetic links of WFs and RSDs confirm a number of genes and gene products are plausible participants in RSD development. Our results are a significant resource to identify causal influences on the development of RSDs, particularly in the context of WF exposure.

Gastric cancer is a cancer in which malignant cell develops in the inner lining of stomach. The mortality risk of gastric cancer increases when several related diseases arise with it as comorbidity. Nowadays, the severities of gastric cancer and its comorbidity is a global health concern. To deal with this issue we implemented a standard analytical approach to identify the genetic profiling of gastric cancer and its comorbidities. For analyzing the genetic profile we used the mRNA-seq and gene expression microarray data from gastric cancer, diabetes, liver cancer, stroke, kidney disease infected tissues and control datasets. We constructed gene disease relationship networks, analyzed pathways, ontologies, protein-protein interaction network of the differentially expressed genes employing neighborhood base benchmarking and multilayer network topology, and finally, we validated our work using two gold benchmark databases (OMIM and dbGAP). We observed that gastric cancer shared 29, 29, 51, and 65 differentially expressed genes with diabetes, liver cancer, stroke, and kidney disease respectively. After analyzing gene expressions, pathways, ontologies and protein-protein interactions, it can be said that there is an association of gastric cancer with diabetes, liver cancer, stroke and kidney disease as comorbidities. This study may be helpful to identify the accurate comorbidities and it can raise awareness about the threatening consequences of gastric cancer among the peoples.

Glioblastoma (GBM) is a common malignant brain tumor which often presents as a comorbidity with central nervous system (CNS) disorders. Both CNS disorders and GBM cells release glutamate and show an abnormality, but differ in cellular behavior. So, their etiology is not well understood, nor is it clear how CNS disorders influence GBM behavior or growth. This led us to employ a quantitative analytical framework to unravel shared differentially expressed genes (DEGs) and cell signaling pathways that could link CNS disorders and GBM using datasets acquired from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA) datasets where normal tissue and disease-affected tissue were examined. After identifying DEGs, we identified disease-gene association networks and signaling pathways and performed gene ontology (GO) analyses as well as hub protein identifications to predict the roles of these DEGs. We expanded our study to determine the significant genes that may play a role in GBM progression and the survival of the GBM patients by exploiting clinical and genetic factors using the Cox Proportional Hazard Model and the Kaplan–Meier estimator. In this study, 177 DEGs with 129 upregulated and 48 downregulated genes were identified. Our findings indicate new ways that CNS disorders may influence the incidence of GBM progression, growth or establishment and may also function as biomarkers for GBM prognosis and potential targets for therapies. Our comparison with gold standard databases also provides further proof to support the connection of our identified biomarkers in the pathology underlying the GBM progression.

Welding generates and releases fumes that are hazardous to human health. Welding fumes (WFs) are a complex mix of metallic oxides, fluorides and silicates that can cause or exacerbate health problems in exposed individuals. In particular, WF inhalation over an extended period carries an increased risk of cancer, but how WFs may influence cancer behaviour or growth is unclear. To address this issue we employed a quantitative analytical framework to identify the gene expression effects of WFs that may affect the subsequent behaviour of the cancers. We examined datasets of transcript analyses made using microarray studies of WF-exposed tissues and of cancers, including datasets from colorectal cancer (CC), prostate cancer (PC), lung cancer (LC) and gastric cancer (GC). We constructed gene-disease association networks, identified signaling and ontological pathways, clustered protein-protein interaction network using multilayer network topology, and analyzed survival function of the significant genes using Cox proportional hazards (Cox PH) model and product-limit (PL) estimator. We observed that WF exposure causes altered expression of many genes (36, 13, 25 and 17 respectively) whose expression are also altered in CC, PC, LC and GC. Gene-disease association networks, signaling and ontological pathways, protein-protein interaction network, and survival functions of the significant genes suggest ways that WFs may influence the progression of CC, PC, LC and GC. This quantitative analytical framework has identified potentially novel mechanisms by which tissue WF exposure may lead to gene expression changes in tissue gene expression that affect cancer behaviour and, thus, cancer progression, growth or establishment.

The Coronavirus Disease 2019 (COVID-19) still tends to propagate and increase the occurrence of COVID-19 across the globe. The clinical and epidemiological analyses indicate the link between COVID-19 and Neurological Diseases (NDs) that drive the progression and severity of NDs. Elucidating why some patients with COVID-19 influence the progression of NDs and patients with NDs who are diagnosed with COVID-19 are becoming increasingly sick, although others are not is unclear. In this research, we investigated how COVID-19 and ND interact and the impact of COVID-19 on the severity of NDs by performing transcriptomic analyses of COVID-19 and NDs samples by developing the pipeline of bioinformatics and network-based approaches. The transcriptomic study identified the contributing genes which are then filtered with cell signaling pathway, gene ontology, protein-protein interactions, transcription factor, and microRNA analysis. Identifying hub-proteins using protein-protein interactions leads to the identification of a therapeutic strategy. Additionally, the incorporation of comorbidity interactions score enhances the identification beyond simply detecting novel biological mechanisms involved in the pathophysiology of COVID-19 and its NDs comorbidities. By computing the semantic similarity between COVID-19 and each of the ND, we have found gene-based maximum semantic score between COVID-19 and Parkinson's disease, the minimum semantic score between COVID-19 and Multiple sclerosis. Similarly, we have found gene ontology-based maximum semantic score between COVID-19 and Huntington disease, minimum semantic score between COVID-19 and Epilepsy disease. Finally, we validated our findings using gold-standard databases and literature searches to determine which genes and pathways had previously been associated with COVID-19 and NDs.

Lung cancer is that kind of disease that can be defined as one of the threating one and has become very challenging these days. In many cases, the cells that carry cancer overlap with each other and its very hard to detect in the initial stage. But fact is, early detection bring solution; it can reduce the death for sure. Throughout the study, we use a technique (GLCM); The Grey Level Cooccurrence for the purpose of extracting the lung images of affected. The detection of abnormal Lung image can be detected by the Support Vector Machine (SVM).

Background Type 2 diabetes (T2D) is an interminable illness that makes many types of genetic dysfunction in the human body, particularly to the nerves, veins, kidneys, liver and uterus. T2D existence in a longer period of time may create the risk of building some comorbidities, however the indication of this risk is inadequately comprehended. To address this issue, we studied the transcriptomic data to recognize the link between T2D and its major comorbidities. Methods We developed a quantitative model to investigate the genetic links between T2D and its significant comorbidities. We analyzed gene expression omnibus (GEO) microarray data from T2D, liver cancer (LC), endometrial cancer (EC), xanthoma (Xa), myocardial infarction (MI), embolic stroke (ES), kidney failure (KF), xerostomia (Xe) and control datasets. We constructed gene-disease association networks (GDN), identified signaling and ontological pathways, formed protein-protein interaction (PPI) network employing neighborhood-based benchmarking and multilayer network topology. Results We observed, T2D shared 22, 15, 18, 21, 12, 14 and 13 differentially expressed genes (DEGs) with LC, EC, Xa, MI, ES, KF, and Xe respectively. DEG investigation, signaling and ontological pathways, and PPI network suggest significant links between T2D and the advancement of LC, EC, Xa, MI, ES, KF, and Xe. Conclusions Our systematic approach to identify the genetic links of T2D with the progression of LC, EC, Xa, MI, ES, KF, and Xe by understanding the causal influences of T2D may be helpful to develop therapeutic strategies for T2D and those comorbidities. This study will also be useful to predict comorbidities occurrence and build human awareness against the dangerous effects of T2D.

BackgroundWelding exposes different types of fumes, gases and radiant energy that can be potentially dangerous for unsafe welder’s health. Welding fumes (WFs) are a significant problem among all those exposed. WFs are a complex mixture of metallic oxides, silicates and fluorides that may result in different health effects. If a welder inhales such fumes in large quantities over a long period of time, there is a risk of various neurodegenerative diseases (NDGDs) development.MethodsWe developed quantitative frameworks to identify the genetic relationship of WFs and NDGDs. We analyzed Gene Expression microarray data from WFs exposed tissues and NDGDs including Parkinson’s disease (PD), Alzheimer’s disease (AD), Lou Gehrig’s disease (LGD), Epilepsy disease (ED), Multiple Sclerosis disease (MSD) datasets. We constructed disease-gene relationship networks and identified dysregulated pathways, ontological path- ways and protein-protein interaction sub-network using multilayer network topology and neighborhood-based benchmarking.ResultsWe observed that WFs shares 18, 16, 13, 19 and 19 differentially expressed genes with PD, AD, LGD, ED and MSD respectively. Gene expression dysregulation along with relationship networks, pathways and ontologic analysis showed that WFs are responsible for the progression of PD, AD, LGD, ED and MSD neurodegenerative diseases.ConclusionOur developed network-based approach to analysis and investigate the genetic effects of welding fumes on PD, AD, LGD, ED and MSD neurodegenerative diseases could be helpful to understand the causal influences of WF exposure for the progression of the NDGDs.

Identification of genes whose regulation of expression is similar in both brain and blood cells could enable monitoring of significant neurological traits and disorders by analysis of blood samples. We thus employed transcriptional analysis of pathologically affected tissues, using agnostic approaches to identify overlapping gene functions and integrating this transcriptomic information with expression quantitative trait loci (eQTL) data. Here, we estimate the correlation of genetic expression in the top-associated cis-eQTLs of brain tissue and blood cells in Parkinson’s (PD).We introduced quantitative frameworks to reveal the complex relationship of various biasing genetic factors in PD, a neurodegenerative disease. We examined gene expression microarray and RNA-Seq datasets from human brain and blood tissues from PD-affected and control individuals. Differentially expressed genes (DEG) were identified for both brain and blood cells to determine common DEG overlaps. Based on neighborhood-based benchmarking and multilayer network topology aproaches we then developed genetic associations of factors with PD.Overlapping DEG sets underwent gene enrichment using pathway analysis and gene ontology methods, which identified candidate common genes and pathways. We identified 12 significantly dysregulated genes shared by brain and blood cells, which were validated using dbGaP (gene SNP-disease linkage) database for gold-standard benchmarking of their significance in disease processes. Ontological and pathway analyses identified significant gene ontology and molecular pathways that indicate PD progression.In sum, we found possible novel links between pathological processes in brain and blood cells by examining cell path-way commonalities, corroborating these associations using well validated datasets. This demonstrates that for brain-related pathologies combining gene expression analysis and blood cell cis-eQTL is a potentially powerful analytical approach. Thus, our methodologies facilitate data-driven approaches that can advance knowledge of disease mechanisms and may enable prediction of neurological dysfunction using blood cell transcript profiling.