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      Identification of pyroptosis-related subtypes and establishment of prognostic model and immune characteristics in asthma

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          Abstract

          Background

          Although studies have shown that cell pyroptosis is involved in the progression of asthma, a systematic analysis of the clinical significance of pyroptosis-related genes (PRGs) cooperating with immune cells in asthma patients is still lacking.

          Methods

          Transcriptome sequencing datasets from patients with different disease courses were used to screen pyroptosis-related differentially expressed genes and perform biological function analysis. Clustering based on K-means unsupervised clustering method is performed to identify pyroptosis-related subtypes in asthma and explore biological functional characteristics of poorly controlled subtypes. Diagnostic markers between subtypes were screened and validated using an asthma mouse model. The infiltration of immune cells in airway epithelium was evaluated based on CIBERSORT, and the correlation between diagnostic markers and immune cells was analyzed. Finally, a risk prediction model was established and experimentally verified using differentially expressed genes between pyroptosis subtypes in combination with asthma control. The cMAP database and molecular docking were utilized to predict potential therapeutic drugs.

          Results

          Nineteen differentially expressed PRGs and two subtypes were identified between patients with mild-to-moderate and severe asthma conditions. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes. Poor control subtypes were closely related to glucocorticoid resistance and airway remodeling. BNIP3 was identified as a diagnostic marker and associated with immune cell infiltration such as, M2 macrophages. The risk prediction model containing four genes has accurate classification efficiency and prediction value. Small molecules obtained from the cMAP database that may have therapeutic effects on asthma are mainly DPP4 inhibitors.

          Conclusion

          Pyroptosis and its mediated immune phenotype are crucial in the occurrence, development, and prognosis of asthma. The predictive models and drugs developed on the basis of PRGs may provide new solutions for the management of asthma.

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          Most cited references57

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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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            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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              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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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                28 July 2022
                2022
                : 13
                : 937832
                Affiliations
                [1] 1 College of Traditional Chinese Medicine, Beijing University of Chinese Medicine , Beijing, China
                [2] 2 National Institute of Traditional Chinese Medicine (TCM) Constitution and Preventive Medicine, Beijing University of Chinese Medicine , Beijing, China
                [3] 3 Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine , Beijing, China
                [4] 4 College of Pharmacy, Shandong University of Traditional Chinese Medicine , Jinan, China
                [5] 5 Department of Clinical Nutrition, Chinese Academy of Medical Sciences - Peking Union Medical College, Peking Union Medical College Hospital , Beijing, China
                [6] 6 College of Traditional Chinese Medicine, Shandong University of Chinese Medicine , Jinan, China
                [7] 7 School of Chinese Medicine, Southern Medical University , Guangzhou, China
                Author notes

                Edited by: Bao-Hui Cheng, Institute of ENT and Shenzhen Key Laboratory of ENT, China

                Reviewed by: Zhe Xing, Zhengzhou University, China; Tao Han, Northern Theater General Hospital, China

                *Correspondence: Ji Wang, doctorwang2009@ 123456126.com ; Xiaoshan Zhao, zhaoxs0609@ 123456163.com

                †These authors have contributed equally to this work

                This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.937832
                9368761
                35967302
                7d0738c0-dfff-418e-9692-205feccd2bb0
                Copyright © 2022 Yang, Wang, Yan, Li, Kong, Zong, Chao, Li, Zhao and Wang

                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
                : 06 May 2022
                : 04 July 2022
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 57, Pages: 15, Words: 5867
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Categories
                Immunology
                Original Research

                Immunology
                pyroptosis-related genes,asthma,prognostic model,immune cell,dpp4
                Immunology
                pyroptosis-related genes, asthma, prognostic model, immune cell, dpp4

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