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      Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma

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          Abstract

          Background

          The coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma.

          Methods

          Two sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury.

          Results

          We discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein–protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor–gene interactions, DEG–microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes.

          Conclusion

          We identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.

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          Most cited references152

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          STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

          Abstract Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein–protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein–protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
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            Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

            Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.
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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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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                23 September 2022
                2022
                23 September 2022
                : 13
                : 988479
                Affiliations
                [1] 1 Affiliated Cancer Hospital and Institute of Guangzhou Medical University , Guangzhou, China
                [2] 2 Department of Anesthesiology, Zhongshan Hospital, Fudan University , Shanghai, China
                [3] 3 Department of Anesthesiology (High-Tech Branch), The First Affiliated Hospital of Anhui Medical University , Hefei, China
                [4] 4 Department of Anesthesiology, Minhang Hospital, Fudan University , Shanghai, China
                Author notes

                Edited by: Weishan Huang, Louisiana State University, United States

                Reviewed by: Linxiang Yin, Harvard Medical School, United States; Jingqi Zhou, Shanghai Jiao Tong University, China

                *Correspondence: Guojun Qian, qianguojun@ 123456gzhmu.edu.cn ; Hao Fang, drfanghao@ 123456163.com

                †These authors have contributed equally to this work

                This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.988479
                9537444
                36211429
                04a59a13-4b34-43ff-941f-d1a9633d64cc
                Copyright © 2022 Fang, Sun, Chen, Chen, Sun, Kong, Fang and Qian

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 July 2022
                : 30 August 2022
                Page count
                Figures: 9, Tables: 4, Equations: 0, References: 152, Pages: 22, Words: 7195
                Categories
                Immunology
                Original Research

                Immunology
                coronavirus disease 2019,allergic asthma,disease biomarker,hub gene,gene ontology,drug,systems-biology,bioinformatics

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