Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches

ABSTRACTThis study aims to analyze Coronavirus Disease 2019 (COVID-19)-associated copper-death genes using the Gene Expression Omnibus (GEO) dataset and machine learning, exploring their immune microenvironment correlation and underlying mechanisms. Utilizing GEO, we analyzed the GSE217948 dataset w...

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Main Authors: Qi Wang, Zhenzhong Su, Jing Zhang, He Yan, Jie Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Human Vaccines & Immunotherapeutics
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2024.2310359
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author Qi Wang
Zhenzhong Su
Jing Zhang
He Yan
Jie Zhang
author_facet Qi Wang
Zhenzhong Su
Jing Zhang
He Yan
Jie Zhang
author_sort Qi Wang
collection DOAJ
description ABSTRACTThis study aims to analyze Coronavirus Disease 2019 (COVID-19)-associated copper-death genes using the Gene Expression Omnibus (GEO) dataset and machine learning, exploring their immune microenvironment correlation and underlying mechanisms. Utilizing GEO, we analyzed the GSE217948 dataset with control samples. Differential expression analysis identified 16 differentially expressed copper-death genes, and Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) quantified immune cell infiltration. Gene classification yielded two copper-death clusters, with Weighted Gene Co-expression Network Analysis (WGCNA) identifying key module genes. Machine learning models (random forest, Support Vector Machine (SVM), Generalized Linear Model (GLM), eXtreme Gradient Boosting (XGBoost)) selected 6 feature genes validated by the GSE213313 dataset. Ferredoxin 1 (FDX1) emerged as the top gene, corroborated by Area Under the Curve (AUC) analysis. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) revealed enriched pathways in T cell receptor, natural killer cytotoxicity, and Peroxisome Proliferator-Activated Receptor (PPAR). We uncovered differentially expressed copper-death genes and immune infiltration differences, notably CD8 T cells and M0 macrophages. Clustering identified modules with potential implications for COVID-19. Machine learning models effectively predicted COVID-19 risk, with FDX1‘s pivotal role validated. FDX1‘s high expression was associated with immune pathways, suggesting its role in COVID-19 pathogenesis. This comprehensive approach elucidated COVID-19-related copper-death genes, their immune context, and risk prediction potential. FDX1‘s connection to immune pathways offers insights into COVID-19 mechanisms and therapy.
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spelling doaj.art-9cd3a3d78d04422e97ca984380d84bea2024-03-12T04:59:26ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2310359Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approachesQi Wang0Zhenzhong Su1Jing Zhang2He Yan3Jie Zhang4Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of General Gynecology, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, ChinaABSTRACTThis study aims to analyze Coronavirus Disease 2019 (COVID-19)-associated copper-death genes using the Gene Expression Omnibus (GEO) dataset and machine learning, exploring their immune microenvironment correlation and underlying mechanisms. Utilizing GEO, we analyzed the GSE217948 dataset with control samples. Differential expression analysis identified 16 differentially expressed copper-death genes, and Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) quantified immune cell infiltration. Gene classification yielded two copper-death clusters, with Weighted Gene Co-expression Network Analysis (WGCNA) identifying key module genes. Machine learning models (random forest, Support Vector Machine (SVM), Generalized Linear Model (GLM), eXtreme Gradient Boosting (XGBoost)) selected 6 feature genes validated by the GSE213313 dataset. Ferredoxin 1 (FDX1) emerged as the top gene, corroborated by Area Under the Curve (AUC) analysis. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) revealed enriched pathways in T cell receptor, natural killer cytotoxicity, and Peroxisome Proliferator-Activated Receptor (PPAR). We uncovered differentially expressed copper-death genes and immune infiltration differences, notably CD8 T cells and M0 macrophages. Clustering identified modules with potential implications for COVID-19. Machine learning models effectively predicted COVID-19 risk, with FDX1‘s pivotal role validated. FDX1‘s high expression was associated with immune pathways, suggesting its role in COVID-19 pathogenesis. This comprehensive approach elucidated COVID-19-related copper-death genes, their immune context, and risk prediction potential. FDX1‘s connection to immune pathways offers insights into COVID-19 mechanisms and therapy.https://www.tandfonline.com/doi/10.1080/21645515.2024.2310359COVID-19differential expression genesbioinformaticsimmune infiltrationWGCNAmachine learning models
spellingShingle Qi Wang
Zhenzhong Su
Jing Zhang
He Yan
Jie Zhang
Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches
Human Vaccines & Immunotherapeutics
COVID-19
differential expression genes
bioinformatics
immune infiltration
WGCNA
machine learning models
title Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches
title_full Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches
title_fullStr Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches
title_full_unstemmed Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches
title_short Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches
title_sort unraveling the copper death connection decoding covid 19 s immune landscape through advanced bioinformatics and machine learning approaches
topic COVID-19
differential expression genes
bioinformatics
immune infiltration
WGCNA
machine learning models
url https://www.tandfonline.com/doi/10.1080/21645515.2024.2310359
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