scholarly journals Host–Viral Interactions Revealed among Shared Transcriptomics Signatures of ARDS and Thrombosis: A Clue into COVID-19 Pathogenesis

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e403-e412
Author(s):  
Aastha Mishra ◽  
Shankar Chanchal ◽  
Mohammad Z. Ashraf

AbstractSevere novel corona virus disease 2019 (COVID-19) infection is associated with a considerable activation of coagulation pathways, endothelial damage, and subsequent thrombotic microvascular injuries. These consistent observations may have serious implications for the treatment and management of this highly pathogenic disease. As a consequence, the anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of two independently publicly available datasets of ARDS and venous thromboembolism (VTE). Datasets GSE76293 and GSE19151 derived from National Centre for Biotechnology Information–Gene Expression Omnibus (NCBI-GEO) database were used for ARDS and VTE, respectively. Integrative meta-analysis of expression data (INMEX) tool preprocessed the datasets and effect size combination with random effect modeling was used for obtaining differentially expressed genes (DEGs). Network construction was done for hub genes and pathway enrichment analysis. Our meta-analysis identified a total of 1,878 significant DEGs among the datasets, which when subjected to enrichment analysis suggested inflammation–coagulation–hypoxemia convolutions in COVID-19 pathogenesis. The top hub genes of our study such as tumor protein 53 (TP53), lysine acetyltransferase 2B (KAT2B), DExH-box helicase 9 (DHX9), REL-associated protein (RELA), RING-box protein 1 (RBX1), and proteasome 20S subunit beta 2 (PSMB2) gave insights into the genes known to be participating in the host–virus interactions that could pave the way to understand the various strategies deployed by the virus to improve its replication and spreading.

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yaowei Li ◽  
Li Li

Abstract Background Ovarian carcinoma (OC) is a common cause of death among women with gynecological cancer. MicroRNAs (miRNAs) are believed to have vital roles in tumorigenesis of OC. Although miRNAs are broadly recognized in OC, the role of has-miR-182-5p (miR-182) in OC is still not fully elucidated. Methods We evaluated the significance of miR-182 expression in OC by using analysis of a public dataset from the Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we downloaded three mRNA datasets of OC and normal ovarian tissues (NOTs), GSE14407, GSE18520 and GSE36668, from GEO to identify differentially expressed genes (DEGs). Then the targeted genes of hsa-miR-182-5p (TG_miRNA-182-5p) were predicted using miRWALK3.0. Subsequently, we analyzed the gene overlaps integrated between DEGs in OC and predicted target genes of miR-182 by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and the prognostic effects of the hub genes were analyzed. Results A common pattern of up-regulation for miR-182 in OC was found in our review of the literature. A total of 268 DEGs, both OC-related and miR-182-related, were identified, of which 133 genes were discovered from the PPI network. A number of DEGs were enriched in extracellular matrix organization, pathways in cancer, focal adhesion, and ECM-receptor interaction. Two hub genes, MCM3 and GINS2, were significantly associated with worse overall survival of patients with OC. Furthermore, we identified covert miR-182-related genes that might participate in OC by network analysis, such as DCN, AKT3, and TIMP2. The expressions of these genes were all down-regulated and negatively correlated with miR-182 in OC. Conclusions Our study suggests that miR-182 is essential for the biological progression of OC.


2019 ◽  
Vol 41 (6) ◽  
pp. 743-750 ◽  
Author(s):  
Ting-Yu Chen ◽  
Yang Liu ◽  
Liang Chen ◽  
Jie Luo ◽  
Chao Zhang ◽  
...  

Abstract Glioma is the most common brain tumor with high mortality. However, there are still challenges for the timely and accurate diagnosis and effective treatment of the tumor. One hundred and twenty-one samples with grades II, III and IV from the Gene Expression Omnibus database were used to construct gene co-expression networks to identify hub modules closely related to glioma grade, and performed pathway enrichment analysis on genes from significant modules. In gene co-expression network constructed by 2345 differentially expressed genes from 121 gene expression profiles for glioma, we identified the black and blue modules that associated with grading. The module preservation analysis based on 118 samples indicates that the two modules were replicable. Enrichment analysis showed that the extracellular matrix genes were enriched for blue module, while cell division genes were enriched for black module. According to survival analysis, 21 hub genes were significantly up-regulated and one gene was significantly down-regulated. What’s more, IKBIP, SEC24D, and FAM46A are the genes with little attention among the 22 hub genes. In this study, IKBIP, SEC24D, and FAM46A related to glioma were mentioned for the first time to the current knowledge, which might provide a new idea for us to study the disease in the future. IKBIP, SEC24D and FAM46A among the 22 hub genes identified that are related to the malignancy degree of glioma might be used as new biomarkers to improve the diagnosis, treatment and prognosis of glioma.


2020 ◽  
Author(s):  
Qiangwei Chi ◽  
Shizuan Chen ◽  
Shaotang Li

Abstract Background Colon cancer is a common tumor of the digestive tract worldwide. Recent researches have revealed that colon cancer exhibits distinct differences in clinical and biological characteristics depending on the location of the tumor. However, the underlying genetic and molecular mechanism of the differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) are not fully understood. This study aimed to identify molecular potential biomarkers and therapeutic targets for precise treatment of right-sided and left-sided colon cancer using bioinformatics analysis. Methods The gene microarray profile, named GSE44076, from the Gene Expression Omnibus (GEO) public database was downloaded and processed to then select differentially expressed genes (DEGs) on the base of two sample groups of RCC and LCC. Also, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) network construction, module analysis, validation of hub genes, and survival analysis. Results Finally, we obtained 2259 DEGs between RCC and LCC, 1300 of which were upregulated in RCC and 945 of which were upregulated in LCC. The results of GO and KEGG analysis of the DEGs indicated that the biological functions of DEGs in RCC and LCC were significantly different. CTLA4, IL10, IL2RB, IFNG, NCAM1, EGFR, MYC, SRC, CUL3, and NCBP2 were identified from the PPI networks as the hub genes of RCC and LCC. Among the hub genes, the log-rank tests for overall survival (OS) and disease free survival (DFS) were applied. Moreover, all hub genes, except CUL3, had differential expression levels of miRNA between tumor group and normal group. Conclusion These hub genes and pathways identified based on bioinformatics analysis might conduce to explain the differences between RCC and LCC, and most of the hub genes were specific to the malignant tissues. Notably, these hub genes, especially the genes associated with immunotherapy such as CTLA4, might be potential specific targets or prognostic markers for precise treatment of colon cancer.


2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.


2021 ◽  
Author(s):  
Mohib kakar ◽  
Muhammad Mehboob ◽  
Muhammad Akram ◽  
Imran Iqbal ◽  
Hafza Ijaz ◽  
...  

Abstract Objective The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Methods GEO contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server Gene Expression Omnibus. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and Functional Enrichment Analysis was performed to extract rational information from a set of DEGs. The Protein-Protein Relationship Networking search method has been used for extracting genes interacting. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. Results We identified the top 10 hub genes through Cytohubba plugin. These genes include Cell Cycle Regulatory Cyclins and Cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. Conclusion In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarkers studies that could promote selective molecular therapy for HCC.


2021 ◽  
Author(s):  
Chao Zhang ◽  
Feng Xu ◽  
Fang Fang

Abstract Background: Sepsis-associated acute lung injury (ALI) is a potentially lethal complication associated with a poor prognosis and high mortality worldwide, especially in the outbreak of COVID-19. However, the fundamental mechanisms of this complication were still not fully elucidated. Thus, we conducted this study to identify hub genes and biological pathways of sepsis-associated ALI, mainly focus on two pathways of LPS and HMGB1. Methods: Gene expression profile GSE3037 were downloaded from Gene Expression Omnibus (GEO) database, including 8 patients with sepsis-induced acute lung injury, with 8 unstimulated blood neutrophils, 8 LPS- induced neutrophils and 8 HMGB1-induced neutrophils. Differentially expressed genes (DEGs) identifications, Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network constructions were performed to obtain hub genes and relevant biological pathways.Results: We identified 534 and 317 DEGs for LPS- and HMGB1-induced ALI, respectively. The biological pathways involved in LPS- and HMGB1-induced ALI were also identified accordingly. By PPI network analysis, we found that ten hub genes for LPS-induced ALI (CXCL8, TNF, IL6, IL1B, ICAM1, CXCL1, CXCL2, IL1A, IL1RN and CXCL3) and another ten hub genes for HMGB1-induced ALI (CCL20, CXCL2, CXCL1, CCL4, CXCL3, CXCL9, CCL21, CXCR6, KNG1 and SST). Furthermore, by combining analysis, the results revealed that genes of TNF, CCL20, IL1B, NFKBIA, CCL4, PTGS2, TNFAIP3, CXCL2, CXCL1 and CXCL3 were potential biomarkers for sepsis-associated ALI. Conclusions: Our study revealed that ten hub genes associated with sepsis-induced ALI were TNF, CCL20, IL1B, NFKBIA, CCL4, PTGS2, TNFAIP3, CXCL2, CXCL1 and CXCL3, which may serve as genetic biomarkers and be further verified in prospective experimental trials.


2022 ◽  
Vol 2022 ◽  
pp. 1-17
Author(s):  
Md. Rakibul Islam ◽  
Lway Faisal Abdulrazak ◽  
Mohammad Khursheed Alam ◽  
Bikash Kumar Paul ◽  
Kawsar Ahmed ◽  
...  

Background. Medulloblastoma (MB) is the most occurring brain cancer that mostly happens in childhood age. This cancer starts in the cerebellum part of the brain. This study is designed to screen novel and significant biomarkers, which may perform as potential prognostic biomarkers and therapeutic targets in MB. Methods. A total of 103 MB-related samples from three gene expression profiles of GSE22139, GSE37418, and GSE86574 were downloaded from the Gene Expression Omnibus (GEO). Applying the limma package, all three datasets were analyzed, and 1065 mutual DEGs were identified including 408 overexpressed and 657 underexpressed with the minimum cut-off criteria of ∣ log   fold   change ∣ > 1 and P < 0.05 . The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways enrichment analyses were executed to discover the internal functions of the mutual DEGs. The outcomes of enrichment analysis showed that the common DEGs were significantly connected with MB progression and development. The Search Tool for Retrieval of Interacting Genes (STRING) database was used to construct the interaction network, and the network was displayed using the Cytoscape tool and applying connectivity and stress value methods of cytoHubba plugin 35 hub genes were identified from the whole network. Results. Four key clusters were identified using the PEWCC 1.0 method. Additionally, the survival analysis of hub genes was brought out based on clinical information of 612 MB patients. This bioinformatics analysis may help to define the pathogenesis and originate new treatments for MB.


2021 ◽  
Author(s):  
Tian-Ao Xie ◽  
Hou-He Li ◽  
Zu-En Lin ◽  
Xiao-Ye Lin ◽  
Xin Meng ◽  
...  

Abstract Background: The Corona Virus Disease 2019 (COVID-19) pandemic poses a serious public health threat to the survival and health of people all over the world. We analyzed related mRNA data and gene expression profiles of human cell lines infected with SARS-CoV-2 obtained from GEO (GSE148729), using bioinformatics tools. Differentially expressed genes (DEGs) of human cells infected with SARS-CoV-2 were identified.Method: The GSE148729 datasets were downloaded from the Gene Expression Omnibus (GEO) database. To explore the Biological significance of DEGs, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the DEGs was performed. Protein-protein interaction (PPI) networks of the DEGs were constructed by using the STRING database. The hub genes were selected using the Cytoscape Software, and a t-test was performed to validate the hub genes.Result: A total of 1241 DEGs were screened, including 1049 up-regulated genes and 192 down-regulated genes. Besides, 10 hub genes were obtained from the PPI network, among which the expression level of CXCL2, Etv7, and HIST1H2BG was found to be statistically significant.Conclusion: In conclusion, bioinformatics analysis reveals genes and cellular pathways that are significantly altered in SARS-CoV-2 infected cells. This is conducive to further guide the clinical study of SARS-CoV-2 and provides new perspectives for vaccine development.


2021 ◽  
Author(s):  
Mohib kakar ◽  
Muhammad Mehboob ◽  
Muhammad Akram ◽  
Imran Iqbal ◽  
Hafza Ijaz ◽  
...  

Abstract The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Gene Expression Omnibus (GEO) contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server GEO. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and functional enrichment analysis was performed to extract rational information from a set of DEGs. The protein-protein relationship networking search method was used for extracting interacting genes. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. We identified the top 10 hub genes through Cytohubba plugin. These genes include cell cycle regulatory cyclins and cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarker studies that could promote selective molecular therapy for HCC.


2020 ◽  
Author(s):  
Weijia Lu ◽  
Yunyu Wu ◽  
CanXiong Lu ◽  
Ting Zhu ◽  
ZhongLu Ren ◽  
...  

Abstract Objective MicroRNAs (MiRNAs) is considered to play an important role in the occurrence and development of ovarian cancer(OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated. Methods Through the analysis of public data sets in Gene Expression Omnibus (GEO) database and literature review, the significance of miR-30a expression in OC is evaluated. Three mRNA datasets of OC and normal ovarian tissue, GSE14407, GSE18520 and GSE36668, were downloaded from GEO to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape, and the effect of HUB gene on the prognosis of OC was analyzed. Results A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1 ,MAPK10, Tp53 and the high expression of YKT ,NSF were related to poor prognosis of OC.


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