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      Identifying of biomarkers associated with gastric cancer based on 11 topological analysis methods of CytoHubba

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          Abstract

          Gastric cancer (GC) is one of the most common types of malignancy. Its potential molecular mechanism has not been clarified. In this study, we aimed to explore potential biomarkers and prognosis-related hub genes associated with GC. The gene chip dataset GSE79973 was downloaded from the GEO datasets and limma package was used to identify the differentially expressed genes (DEGs). A total of 1269 up-regulated and 330 down-regulated genes were identified. The protein-protein interactions (PPI) network of DEGs was constructed by STRING V11 database, and 11 hub genes were selected through intersection of 11 topological analysis methods of CytoHubba in Cytoscape plug-in. All the 11 selected hub genes were found in the module with the highest score from PPI network of all DEGs by the molecular complex detection (MCODE) clustering algorithm. In order to explore the role of the 11 hub genes, we performed GO function and KEGG pathway analysis for them and found that the genes were enriched in a variety of functions and pathways among which cellular senescence, cell cycle, viral carcinogenesis and p53 signaling pathway were the most associated with GC. Kaplan-Meier analysis revealed that 10 out of the 11 hub genes were related to the overall survival of GC patients. Further, seven of the 11 selected hub genes were verified significantly correlated with GC by uni- or multivariable Cox model and LASSO regression analysis including C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1. C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1 may serve as potential prognostic biomarkers and therapeutic targets for GC.

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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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            Cytoscape: a software environment for integrated models of biomolecular interaction networks.

            Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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              STRING v10: protein–protein interaction networks, integrated over the tree of life

              The many functional partnerships and interactions that occur between proteins are at the core of cellular processing and their systematic characterization helps to provide context in molecular systems biology. However, known and predicted interactions are scattered over multiple resources, and the available data exhibit notable differences in terms of quality and completeness. The STRING database (http://string-db.org) aims to provide a critical assessment and integration of protein–protein interactions, including direct (physical) as well as indirect (functional) associations. The new version 10.0 of STRING covers more than 2000 organisms, which has necessitated novel, scalable algorithms for transferring interaction information between organisms. For this purpose, we have introduced hierarchical and self-consistent orthology annotations for all interacting proteins, grouping the proteins into families at various levels of phylogenetic resolution. Further improvements in version 10.0 include a completely redesigned prediction pipeline for inferring protein–protein associations from co-expression data, an API interface for the R computing environment and improved statistical analysis for enrichment tests in user-provided networks.
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                Author and article information

                Contributors
                zhangxu1107@163.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                14 January 2021
                14 January 2021
                2021
                : 11
                : 1331
                Affiliations
                [1 ]GRID grid.263906.8, School of Mathematics and Statistics, , Southwest University, ; Chongqing, 400715 China
                [2 ]Department of Pediatric Respiration, Chongqing Ninth People’s Hospital, Chongqing, 400700 China
                [3 ]GRID grid.440649.b, ISNI 0000 0004 1808 3334, School of Science, , Southwest University of Science and Technology, ; Sichuan, 621000 China
                Article
                79235
                10.1038/s41598-020-79235-9
                7809423
                33446695
                2bf8564e-2f51-4ce2-bd75-aafd707377e9
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 January 2020
                : 2 December 2020
                Funding
                Funded by: the Natural Science Foundation of China
                Award ID: No.11701471
                Award Recipient :
                Funded by: Basic Science and Frontier Technology Research Project of Chongqing
                Award ID: cstc2017jcyjAX0476
                Award Recipient :
                Categories
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                © The Author(s) 2021

                Uncategorized
                computational biology and bioinformatics,mathematics and computing
                Uncategorized
                computational biology and bioinformatics, mathematics and computing

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