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      Identification of purity and prognosis‐related gene signature by network analysis and survival analysis in brain lower grade glioma

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          Abstract

          Tumour microenvironment of brain lower grade glioma (LGG) consists of non‐tumour cells including stromal cells and immune cells mainly. These non‐tumour cells dilute the purity of LGG and play pivotal roles in tumour growth and development, thereby affecting patient prognosis. Tumour purity is also associated with molecular subtypes of LGG. In this study, we discovered the most relevant module to purity by weighted gene co‐expression network analysis (WGCNA) and afterwards performed consensus network analysis and survival analysis to filter 61 significant genes related to both purity and prognosis. In turn, we built a simplified model based on the calculation of purity score, and consensus measurement of purity estimation (CPE), with a satisfactory predictive performance by random forest regression. HLA‐E, MSN, GNG‐5, MYL12A, ITGB4, PDPN, AGTRAP, S100A4, PLSCR1, VAMP5 were selected as the most relevant genes correlating to both purity and prognosis. The risk score model based on the 10 genes could moderately predict patients’ overall survival. These 10 genes, respectively, were positively correlated positively to immunosuppressive cells like macrophage M2, but negatively correlated to patient prognosis, which may explain partially the poor prognosis with low‐purity group.

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          clusterProfiler: an R package for comparing biological themes among gene clusters.

          Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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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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              Robust enumeration of cell subsets from tissue expression profiles

              We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA mixtures for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).
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                Author and article information

                Contributors
                lxjneuro@csu.edu.cn
                Journal
                J Cell Mol Med
                J Cell Mol Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                31 August 2020
                October 2020
                : 24
                : 19 ( doiID: 10.1111/jcmm.v24.19 )
                : 11607-11612
                Affiliations
                [ 1 ] Department of Neurosurgery Xiangya Hospital Central South University Changsha P. R. China
                [ 2 ] Xiangya School of Medicine Central South University Changsha P. R. China
                [ 3 ] Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research Xiangya Hospital Central South University Changsha P. R. China
                Author notes
                [*] [* ] Correspondence

                Xuejun Li, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.

                Email: lxjneuro@ 123456csu.edu.cn

                Author information
                https://orcid.org/0000-0003-2943-1931
                Article
                JCMM15805
                10.1111/jcmm.15805
                7576230
                32869484
                f988ecb2-43c9-4588-9d86-d9b7578fd637
                © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 September 2019
                : 30 July 2020
                : 05 August 2020
                Page count
                Figures: 2, Tables: 0, Pages: 6, Words: 2884
                Funding
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81472594 81770781
                Categories
                Short Communication
                Short Communications
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:21.10.2020

                Molecular medicine
                Molecular medicine

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