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      Identification of Important Modules and Hub Gene in Chronic Kidney Disease Based on WGCNA

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          Abstract

          Chronic kidney disease (CKD) is an ongoing deterioration of renal function that often progresses to end-stage renal disease. In this study, we aimed to screen and identify potential key genes for CKD using the weighted gene coexpression network (WGCNA) analysis tool. Gene expression data related to CKD were screened from GEO database, and expression datasets of GSE66494 and GSE62792 were obtained. After discrete analysis of samples, WGCNA analysis was performed to construct gene coexpression module, and the correlation between the module and disease was calculated. The modules with a significant correlation with the disease were selected for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Then, the interaction network of related molecules was constructed, and the high score subnetwork was selected, and the candidate key molecules were identified. A total of 882 DEGs were identified in the screening datasets. A subnetwork containing 6 nodes was found with a high score of 12.08, including CEBPZ, IFI16, LYAR, BRIX1, BMS1, and DDX18. DEGs could significantly differentiate CKD and healthy individuals in principal component analysis. In addition, the MEturquiose, MEred, and MEblue in group were significantly correlated with disease in WGCNA. These 6 hub genes were found to significantly discriminate between CKD and healthy controls in the validation dataset, suggesting that they could use these molecules as candidate markers to distinguish CKD from healthy people. Overall, our study indicated that 6 hub genes may play key roles in the occurrence and development of CKD.

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          Most cited references26

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          WGCNA: an R package for weighted correlation network analysis

          Background Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. Results The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. Conclusion The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at .
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            NCBI GEO: archive for functional genomics data sets—update

            The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.
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              K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

              (2002)
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                Author and article information

                Contributors
                Journal
                J Immunol Res
                J Immunol Res
                jir
                Journal of Immunology Research
                Hindawi
                2314-8861
                2314-7156
                2022
                4 May 2022
                : 2022
                : 4615292
                Affiliations
                Clinical Laboratory, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai, China
                Author notes

                Academic Editor: Fu Wang

                Author information
                https://orcid.org/0000-0003-0701-8046
                Article
                10.1155/2022/4615292
                9095404
                35571562
                0e99fd2e-eee5-45b8-83fb-0803f082513a
                Copyright © 2022 Jia Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 March 2022
                : 16 April 2022
                : 18 April 2022
                Funding
                Funded by: Traditional Chinese Medicine Scientific Research Project of Shanghai Hongkou District Health Commission in 2020
                Award ID: HKQ-ZYY-2020-33
                Categories
                Research Article

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