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      Comprehensive Analysis of Potential ceRNA Network and Different Degrees of Immune Cell Infiltration in Acute Respiratory Distress Syndrome

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          Abstract

          Acute respiratory distress syndrome (ARDS) is a leading cause of death in critically ill patients due to hypoxemic respiratory failure. The specific pathogenesis underlying ARDS has not been fully elucidated. In this study, we constructed a triple regulatory network involving competing endogenous RNA (ceRNA) to investigate the potential mechanism of ARDS and evaluated the immune cell infiltration patterns in ARDS patients. Overall, we downloaded three microarray datasets that included 60 patients with sepsis-induced ARDS and 79 patients with sepsis alone from the public Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs, including 9 DElncRNAs, 9 DEmiRNAs, and 269 DEmRNAs) by R software. The DEGs were subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional enrichment analysis, and a protein–protein interaction (PPI) network was generated for uncovering interactive relationships among DEmRNAs. Then, a ceRNA network that contained 5 DElncRNAs, 7 DEmiRNAs, and 71 DEmRNAs was established according to the overlapping genes in both DEGs and predicted genes by public databases. Finally, we identified the TUG1/miR-140-5p/NFE2L2 pathway as the hub pathway in the whole network through Cytoscape. In addition, we evaluated the distribution of 22 subtypes of immune cells and recognized three differentially expressed immune cells in patients with sepsis-induced ARDS by “Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)” algorithm, namely, naive B cells, regulatory T cells, and eosinophils. Correlations between differentially expressed immune cells and hub genes in the ceRNA network were also performed. In conclusion, we demonstrated a new potential regulatory mechanism underlying ARDS (the TUG1/miR-140-5p/NFE2L2 ceRNA regulatory pathway), which may help in further exploring the pathogenesis of ARDS.

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          Most cited references69

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          limma powers differential expression analyses for RNA-sequencing and microarray studies

          limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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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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              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
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                01 June 2022
                2022
                : 13
                : 895629
                Affiliations
                Department of Respiratory and Critical Care Medicine , Beijing Anzhen Hospital , Capital Medical University , Beijing, China
                Author notes

                Edited by: Pu-Feng Du, Tianjin University, China

                Reviewed by: Cheng Liang, Shandong Normal University, China

                Qi Zhao, University of Science and Technology Liaoning, China

                *Correspondence: Guangfa Zhu, guangfa_zhu@ 123456ccmu.edu.cn

                This article was submitted to Computational Genomics, a section of the journal Frontiers in Genetics

                Article
                895629
                10.3389/fgene.2022.895629
                9198558
                497935bf-5c3c-4c02-9a2b-5798c1a99c5b
                Copyright © 2022 Hu, Ge, Sun, Ren, Xie and Zhu.

                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
                : 14 March 2022
                : 04 April 2022
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Categories
                Genetics
                Original Research

                Genetics
                acute respiratory distress syndrome—ards,sepsis,immune infiltration,competitive endogenous rna (cerna) network,bioinformatic analysis

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