scholarly journals Identification of Infertility-Associated Topologically Important Genes Using Weighted Co-expression Network Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingni Wu ◽  
Xiaomeng Xia ◽  
Ye Hu ◽  
Xiaoling Fang ◽  
Sandra Orsulic
Keyword(s):  
Network Analysis ◽  
Topological Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Messenger Rnas ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Highly Correlated

Endometriosis has been associated with a high risk of infertility. However, the underlying molecular mechanism of infertility in endometriosis remains poorly understood. In our study, we aimed to discover topologically important genes related to infertility in endometriosis, based on the structure network mining. We used microarray data from the Gene Expression Omnibus (GEO) database to construct a weighted gene co-expression network for fertile and infertile women with endometriosis and to identify gene modules highly correlated with clinical features of infertility in endometriosis. Additionally, the protein–protein interaction network analysis was used to identify the potential 20 hub messenger RNAs (mRNAs) while the network topological analysis was used to identify nine candidate long non-coding RNAs (lncRNAs). Functional annotations of clinically significant modules and lncRNAs revealed that hub genes might be involved in infertility in endometriosis by regulating G protein-coupled receptor signaling (GPCR) activity. Gene Set Enrichment Analysis showed that the phospholipase C-activating GPCR signaling pathway is correlated with infertility in patients with endometriosis. Taken together, our analysis has identified 29 hub genes which might lead to infertility in endometriosis through the regulation of the GPCR network.

Identification of IL-6 as a potential mediator of the myocardial fibrosis that occurs in response to surgery with cardiopulmonary bypass in children with Tetralogy of Fallot

2021 ◽  
pp. 1-7
Author(s):  
Hongtao Liu ◽  
Yun Zhang ◽  
Zhenhai Wu ◽  
Liangqing Zhang
Keyword(s):  
Heart Failure ◽  
Network Analysis ◽  
Myocardial Fibrosis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Gene Correlation ◽  
Cell Expression

Abstract Background: Tetralogy of Fallot is a common CHD. Studies have shown a close link between heart failure and myocardial fibrosis. Interleukin-6 has been suggested to be a post-independent factor of heart failure. This study aimed to explore the relationship between IL-6 and myocardial fibrosis during cardiopulmonary bypass. Material and Methods: We downloaded the expression profile dataset GSE132176 from Gene Expression Omnibus. After normalising the raw data, Gene Set Enrichment Analysis and differential gene expression analysis were performed using R. Further, a weighted gene correlation network analysis and a protein–protein interaction network analysis were used to identify HUB genes. Finally, we downloaded single-cell expression data for HUB genes using PanglaoDB. Results: There were 119 differentially expressed genes in right atrium tissues comparing the post-CPB group with the pre-CPB group. IL-6 was found to be significantly up-regulated in the post-CPB group. Six genes (JUN, FOS, ATF3, EGR1, IL-6, and PTGS2) were identified as HUB genes by a weighted gene correlation network analysis and a protein–protein interaction network analysis. Gene Set Enrichment Analysis showed that IL-6 affects the myocardium during CPB mainly through the JAK/STAT signalling pathway. Finally, we used PanglaoDB data to analyse the single-cell expression of the HUB genes. Conclusion: Our findings suggest that high expression of IL-6 and the activation of the JAK/STAT signalling pathway during CPB maybe the potential mechanism of myocardial fibrosis. We speculate that the high expression of IL-6 might be an important factor leading to heart failure after ToF surgery. We expect that these findings will provide a basis for the development of targeted drugs.

scholarly journals Ten genes are considered as potential biomarkers for the diagnosis of dermatomyositis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260511
Author(s):  
Lu Xiao ◽  
Wei Xiao ◽  
Shudian Lin
Keyword(s):  
Characteristic Curve ◽  
Area Under The Curve ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Type I ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Healthy Control ◽  
Potential Biomarkers

Objective This study aimed to identify the biomarkers and mechanisms for dermatomyositis (DM) progression at the transcriptome level through a combination of microarray and bioinformatic analyses. Method Microarray datasets for skeletal muscle of DM and healthy control (HC) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by using GEO2R. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein–protein interaction network was constructed to identify hub genes. The top 10 hub genes were validated by other GEO datasets. The diagnostic accuracy of the top 10 hub genes for DM was evaluated using the area under the curve of the receiver operating characteristic curve. Result A total of 63 DEGs were identified between 10 DM samples and 9 HC samples. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that DEGs are mostly enriched in response to virus, defense response to virus, and type I interferon signaling pathway. 10 hub genes and 3 gene cluster modules were identified by Cytoscape. The identified hub genes were verified by GSE1551 and GSE11971 datasets and proven to be potential biomarkers for the diagnosis of DM. Conclusion Our work identified 10 valuable genes as potential biomarkers for the diagnosis of DM and explored the potential underlying molecular mechanism of the disease.

scholarly journals Comprehensive Analysis of Pertinent Genes and Pathways in Atrial Fibrillation

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yanzhe Wang ◽  
Wenjuan Cai ◽  
Liya Gu ◽  
Xuefeng Ji ◽  
Qiusheng Shen
Keyword(s):  
Atrial Fibrillation ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Cell Counting ◽  
Ppi Network ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Protein Protein Interaction ◽  
Endothelial Growth Factor

Purpose. Atrial fibrillation (AF) is the most frequent arrhythmia in clinical practice. The pathogenesis of AF is not yet clear. Therefore, exploring the molecular information of AF displays much importance for AF therapy. Methods. The GSE2240 data were acquired from the Gene Expression Omnibus (GEO) database. The R limma software package was used to screen DEGs. Based on the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) databases, we conducted the functions and pathway enrichment analyses. Then, the STRING and Cytoscape software were employed to build Protein-Protein Interaction (PPI) network and screen for hub genes. Finally, we used the Cell Counting Kit-8 (CCK-8) experiment to explore the effect of hub gene knockdown on the proliferation of AF cells. Result. 906 differentially expressed genes (DEGs), including 542 significantly upregulated genes and 364 significantly downregulated genes, were screened in AF. The genes of AF were mainly enriched in vascular endothelial growth factor-activated receptor activity, alanine, regulation of histone deacetylase activity, and HCM. The PPI network constructed of significantly upregulated DEGs contained 404 nodes and 514 edges. Five hub genes, ASPM, DTL, STAT3, ANLN, and CDCA5, were identified through the PPI network. The PPI network constructed by significantly downregulated genes contained 327 nodes and 301 edges. Four hub genes, CDC42, CREB1, AR, and SP1, were identified through this PPI network. The results of CCK-8 experiments proved that knocking down the expression of CDCA5 gene could inhibit the proliferation of H9C2 cells. Conclusion. Bioinformatics analyses revealed the hub genes and key pathways of AF. These genes and pathways provide information for studying the pathogenesis, treatment, and prognosis of AF and have the potential to become biomarkers in AF treatment.

scholarly journals Feature selection with the Fisher score followed by the Maximal Clique Centrality algorithm can accurately identify the hub genes of hepatocellular carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chengzhang Li ◽  
Jiucheng Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Random Forest ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Maximal Clique ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
Fisher Score ◽  
Protein Protein Interaction ◽  
Kaplan Meier

AbstractThis study aimed to select the feature genes of hepatocellular carcinoma (HCC) with the Fisher score algorithm and to identify hub genes with the Maximal Clique Centrality (MCC) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to examine the enrichment of terms. Gene set enrichment analysis (GSEA) was used to identify the classes of genes that are overrepresented. Following the construction of a protein-protein interaction network with the feature genes, hub genes were identified with the MCC algorithm. The Kaplan–Meier plotter was utilized to assess the prognosis of patients based on expression of the hub genes. The feature genes were closely associated with cancer and the cell cycle, as revealed by GO, KEGG and GSEA enrichment analyses. Survival analysis showed that the overexpression of the Fisher score–selected hub genes was associated with decreased survival time (P < 0.05). Weighted gene co-expression network analysis (WGCNA), Lasso, ReliefF and random forest were used for comparison with the Fisher score algorithm. The comparison among these approaches showed that the Fisher score algorithm is superior to the Lasso and ReliefF algorithms in terms of hub gene identification and has similar performance to the WGCNA and random forest algorithms. Our results demonstrated that the Fisher score followed by the application of the MCC algorithm can accurately identify hub genes in HCC.

scholarly journals BPI and KIR6.1 as significant hub genes for vein graft restenosis

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096933
Author(s):  
Yun-peng Bai ◽  
Bo-chen Yao ◽  
Mei Wang ◽  
Xian-kun Liu ◽  
Xiao-long Zhu ◽  
...  
Keyword(s):  
Vein Graft ◽  
Area Under The Curve ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Protein Protein Interaction

Background Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients. Methods This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Gene Expression Omnibus database. A repeatability test for the GSE110398 dataset was performed using R language. This included the identification of differentially expressed genes (DEGs), enrichment analysis via Metascape software, pathway enrichment analysis, and construction of a protein–protein interaction network and a hub gene network. Results Twenty-four DEGs were identified between VGR and control groups. The four most important hub genes ( KIR6.1, PCLP1, EDNRB, and BPI) were identified, and Pearson’s correlation coefficient showed that KIR6.1 and BPI were significantly correlated with VGR. KIR6.1 could also sensitively predict VGR (0.9 < area under the curve ≤1). Conclusion BPI and KIR6.1 were differentially expressed in vessels with and without stenosis after vascular transplantation, suggesting that these genes or their encoded proteins may be involved in the occurrence of VGR.

scholarly journals Transcriptome Research of Key Modules and Hub Genes Associated with Primary Myelofibrosis by Weighted Co-expression Network Analysis.

2020 ◽  
Author(s):  
Weihang Li ◽  
Bin Yuan ◽  
Shilei Zhang ◽  
Ziyi Ding ◽  
Yingjing Zhao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Network Analysis ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Primary Myelofibrosis ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes

Abstract Background: This study aimed to identify novel targets of diagnosis, therapy as well as prognosis for primary myelofibrosis (PMF).Methods: The gene expression profiles of GSE26049 was obtained from GEO dataset, weighted gene co-expression network analysis (WGCNA) was then performed to identify the most related modules with PMF. Subsequently, GO (Gene Ontology), KEGG (Kyoto Encyclopedia Genes and Genomes), GSEA (Gene Set Enrichment Analysis) and PPI (Protein-Protein Interaction) network were conducted to fully understand the detailed information of the green module.Results: Green module was strongly correlated with PMF disease after WGCNA analysis. 20 genes in green module were identified as hub genes responsible for the progression of PMF. Functional annotation and pathway analysis revealed that these hub genes were primarily enriched in erythrocyte differentiation, transcription factor binding, hemoglobin complex, transcription factor complex and cell cycle et al. Of which, EPB42, CALR, SLC4A1 and MPL had the most correlations with PMF.Conclusions: This study elucidated that genes EPB42, CALR, SLC4A1 and MPL were significantly more highly expressed in PMF samples than in normal samples. These four genes may be considered candidate prognostic biomarkers and potential therapeutic targets for early stage of PMF. Meanwhile, EPB42 and SLC4A1 were firstly found to be highly correlated with the progression of PMF.

scholarly journals Identification of Hub Genes and Pathways Associated With Idiopathic Pulmonary Fibrosis via Bioinformatics Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hanxi Wan ◽  
Xinwei Huang ◽  
Peilin Cong ◽  
Mengfan He ◽  
Aiwen Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Ppi Network ◽  
Hub Genes ◽  
Expression Levels ◽  
Protein Protein Interaction

Idiopathic pulmonary fibrosis (IPF) is a progressive disease whose etiology remains unknown. The purpose of this study was to explore hub genes and pathways related to IPF development and prognosis. Multiple gene expression datasets were downloaded from the Gene Expression Omnibus database. Weighted correlation network analysis (WGCNA) was performed and differentially expressed genes (DEGs) identified to investigate Hub modules and genes correlated with IPF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis were performed on selected key genes. In the PPI network and cytoHubba plugin, 11 hub genes were identified, including ASPN, CDH2, COL1A1, COL1A2, COL3A1, COL14A1, CTSK, MMP1, MMP7, POSTN, and SPP1. Correlation between hub genes was displayed and validated. Expression levels of hub genes were verified using quantitative real-time PCR (qRT-PCR). Dysregulated expression of these genes and their crosstalk might impact the development of IPF through modulating IPF-related biological processes and signaling pathways. Among these genes, expression levels of COL1A1, COL3A1, CTSK, MMP1, MMP7, POSTN, and SPP1 were positively correlated with IPF prognosis. The present study provides further insights into individualized treatment and prognosis for IPF.

scholarly journals Investigation of hub gene associated with the infection of Staphylococcus aureus via weighted gene co-expression network analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia-xin Li ◽  
Xun-jie Cao ◽  
Yuan-yi Huang ◽  
Ya-ping Li ◽  
Zi-yuan Yu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Network Analysis ◽  
Roc Curve ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
Hub Gene ◽  
Protein Protein Interaction ◽  
Serious Infection ◽  
Diagnostic Values

Abstract Introduction Staphylococcus aureus is a gram-positive bacterium that causes serious infection. With the increasing resistance of bacteria to current antibiotics, it is necessary to learn more about the molecular mechanism and cellular pathways involved in the Staphylococcus aureus infection. Methods We downloaded the GSE33341 dataset from the GEO database and applied the weighted gene co-expression network analysis (WGCNA), from which we obtained some critical modules. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were applied to illustrate the biological functions of genes in these modules. We constructed the protein-protein interaction (PPI) network by Cytoscape and selected five candidate hub genes. Five potential hub genes were validated in GSE30119 by GraphPad Prism 8.0. The diagnostic values of these genes were calculated and present in the ROC curve based on the GSE13670 dataset. Their gene functions were analyzed by Gene Set Enrichment Analysis (GSEA). Results A co-expression network was built with 5000 genes divided into 11 modules. The genes in green and turquoise modules demonstrated a high correlation. According to the KEGG and GO analyses, genes in the green module were closely related to ubiquitination and autophagy. Subsequently, we picked out the top five hub genes in the green module. And UBB was determined as the hub gene in the GSE30119 dataset. The expression level of UBB, ASB, and MKRN1 could significantly differentiate between Staphylococcus aureus infection and healthy controls based on the ROC curve. The GSEA analysis indicated that lower expression levels of UBB were associated with the P53 signal pathway. Conclusions We identified some hub genes and significant signal enrichment pathways in Staphylococcus aureus infection via bioinformatics analysis, which may facilitate the development of potential clinical therapeutic strategies.

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