Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves multiple systems. SLE is characterized by the production of autoantibodies and inflammatory tissue damage. This study further explored the role of immune-related genes in SLE. We downloaded the expression profiles of GS...

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Main Authors: Su Zhang, Weitao Hu, Yuchao Tang, Hongjie Lin, Xiaoqing Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1557307/full
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author Su Zhang
Weitao Hu
Yuchao Tang
Hongjie Lin
Xiaoqing Chen
author_facet Su Zhang
Weitao Hu
Yuchao Tang
Hongjie Lin
Xiaoqing Chen
author_sort Su Zhang
collection DOAJ
description Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves multiple systems. SLE is characterized by the production of autoantibodies and inflammatory tissue damage. This study further explored the role of immune-related genes in SLE. We downloaded the expression profiles of GSE50772 using the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) in SLE. The DEGs were also analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The gene modules most closely associated with SLE were then derived by Weighted Gene Co-expression Network Analysis (WGCNA). Differentially expressed immune-related genes (DE-IRGs) in SLE were obtained by DEGs, key gene modules and IRGs. The protein–protein interaction (PPI) network was constructed through the STRING database. Three machine learning algorithms were applied to DE-IRGs to screen for hub DE-IRGs. Then, we constructed a diagnostic model. The model was validated by external cohort GSE61635 and peripheral blood mononuclear cells (PBMC) from SLE patients. Immune cell abundance assessment was achieved by CIBERSORT. The hub DE-IRGs and miRNA networks were made accessible through the NetworkAnalyst database. We screened 945 DEGs, which are closely related to the type I interferon pathway and NOD-like receptor signaling pathway. Machine learning identified a total of five hub DE-IRGs (CXCL2, CXCL8, FOS, NFKBIA, CXCR2), and validated in GSE61635 and PBMC from SLE patients. Immune cell abundance analysis showed that the hub genes may be involved in the development of SLE by regulating immune cells (especially neutrophils). In this study, we identified five hub DE-IRGs in SLE and constructed an effective predictive model. These hub genes are closely associated with immune cell in SLE. These may provide new insights into the immune-related pathogenesis of SLE.
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spelling doaj-art-9ec41492011345ac8381605f284837862025-08-20T03:09:48ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-05-011210.3389/fmed.2025.15573071557307Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learningSu Zhang0Weitao Hu1Yuchao Tang2Hongjie Lin3Xiaoqing Chen4Department of Rheumatology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaDepartment of Rheumatology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaSystemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves multiple systems. SLE is characterized by the production of autoantibodies and inflammatory tissue damage. This study further explored the role of immune-related genes in SLE. We downloaded the expression profiles of GSE50772 using the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) in SLE. The DEGs were also analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The gene modules most closely associated with SLE were then derived by Weighted Gene Co-expression Network Analysis (WGCNA). Differentially expressed immune-related genes (DE-IRGs) in SLE were obtained by DEGs, key gene modules and IRGs. The protein–protein interaction (PPI) network was constructed through the STRING database. Three machine learning algorithms were applied to DE-IRGs to screen for hub DE-IRGs. Then, we constructed a diagnostic model. The model was validated by external cohort GSE61635 and peripheral blood mononuclear cells (PBMC) from SLE patients. Immune cell abundance assessment was achieved by CIBERSORT. The hub DE-IRGs and miRNA networks were made accessible through the NetworkAnalyst database. We screened 945 DEGs, which are closely related to the type I interferon pathway and NOD-like receptor signaling pathway. Machine learning identified a total of five hub DE-IRGs (CXCL2, CXCL8, FOS, NFKBIA, CXCR2), and validated in GSE61635 and PBMC from SLE patients. Immune cell abundance analysis showed that the hub genes may be involved in the development of SLE by regulating immune cells (especially neutrophils). In this study, we identified five hub DE-IRGs in SLE and constructed an effective predictive model. These hub genes are closely associated with immune cell in SLE. These may provide new insights into the immune-related pathogenesis of SLE.https://www.frontiersin.org/articles/10.3389/fmed.2025.1557307/fullbioinformaticshub genesimmune cellmachine learningsystemic lupus erythematosus
spellingShingle Su Zhang
Weitao Hu
Yuchao Tang
Hongjie Lin
Xiaoqing Chen
Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning
Frontiers in Medicine
bioinformatics
hub genes
immune cell
machine learning
systemic lupus erythematosus
title Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning
title_full Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning
title_fullStr Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning
title_full_unstemmed Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning
title_short Identification of hub immune-related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning
title_sort identification of hub immune related genes and construction of predictive models for systemic lupus erythematosus by bioinformatics combined with machine learning
topic bioinformatics
hub genes
immune cell
machine learning
systemic lupus erythematosus
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1557307/full
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