{"title":"强直性脊柱炎的氧化磷酸化途径:多组学分析和机器学习","authors":"Yuling Chen, Yuan Xu, Shuangyan Cao, Qing Lv, Yuanchun Ye, Jieruo Gu","doi":"10.1111/1756-185X.70175","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, characterized by immune microenvironment dysregulation and elevated cytokines like TNF-α and IL-17. Mitochondrial oxidative phosphorylation (OXPHOS), crucial for immune cell function and survival, is implicated in AS pathogenesis. This study explores OXPHOS-related mechanisms in AS, identifies key genes using machine learning, and highlights potential therapeutic targets for precision medicine.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>Peripheral blood mononuclear cells (PBMCs) bulk transcriptomic and single-cell RNA sequencing (scRNA-seq) data from AS patients were analyzed to investigate the role of the OXPHOS pathway in AS. Weighted gene co-expression network analysis (WGCNA) was performed to identify key gene modules associated with OXPHOS. Machine learning techniques, including support vector machine with recursive feature elimination (SVM-RFE), random forest, and least absolute shrinkage and selection operator (LASSO), were applied to identify significant AS-related genes. Real-time PCR (RT-PCR) was used to quantify gene expression, examine their patterns in specific cell subtypes, and explore their functional implications.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Pathway enrichment analysis identified OXPHOS as a significantly enriched pathway distinguishing AS patients from healthy controls, with high normalized enrichment scores and significant group separation in principal component analysis. ScRNA-seq revealed significantly higher OXPHOS scores in AS patients, especially in dendritic cells (DCs) and monocytes, highlighting cell type-specific dysregulation. WGCNA identified two key gene modules (MEyellow and MEtan) that are closely associated with OXPHOS. Three hub genes—<i>LAMTOR2</i>, <i>APBB1IP</i>, and <i>DGKQ</i>—were screened using machine learning methods and validated by RT-PCR and scRNA-seq. Among them, <i>LAMTOR2</i> was significantly more highly expressed in patients with AS, and functional analyses showed that it plays a role in promoting TH17 cell differentiation, which highlights its potential as a therapeutic target for ankylosing spondylitis.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This multi-omics study provides valuable insights into the complex interplay between OXPHOS and AS. The identified genes, particularly <i>LAMTOR2</i>, serve as potential therapeutic targets, contributing to our understanding of AS mechanisms and paving the way for precision medicine in AS treatment.</p>\n </section>\n </div>","PeriodicalId":14330,"journal":{"name":"International Journal of Rheumatic Diseases","volume":"28 5","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oxidative Phosphorylation Pathway in Ankylosing Spondylitis: Multi-Omics Analysis and Machine Learning\",\"authors\":\"Yuling Chen, Yuan Xu, Shuangyan Cao, Qing Lv, Yuanchun Ye, Jieruo Gu\",\"doi\":\"10.1111/1756-185X.70175\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, characterized by immune microenvironment dysregulation and elevated cytokines like TNF-α and IL-17. Mitochondrial oxidative phosphorylation (OXPHOS), crucial for immune cell function and survival, is implicated in AS pathogenesis. This study explores OXPHOS-related mechanisms in AS, identifies key genes using machine learning, and highlights potential therapeutic targets for precision medicine.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and Methods</h3>\\n \\n <p>Peripheral blood mononuclear cells (PBMCs) bulk transcriptomic and single-cell RNA sequencing (scRNA-seq) data from AS patients were analyzed to investigate the role of the OXPHOS pathway in AS. Weighted gene co-expression network analysis (WGCNA) was performed to identify key gene modules associated with OXPHOS. Machine learning techniques, including support vector machine with recursive feature elimination (SVM-RFE), random forest, and least absolute shrinkage and selection operator (LASSO), were applied to identify significant AS-related genes. Real-time PCR (RT-PCR) was used to quantify gene expression, examine their patterns in specific cell subtypes, and explore their functional implications.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Pathway enrichment analysis identified OXPHOS as a significantly enriched pathway distinguishing AS patients from healthy controls, with high normalized enrichment scores and significant group separation in principal component analysis. ScRNA-seq revealed significantly higher OXPHOS scores in AS patients, especially in dendritic cells (DCs) and monocytes, highlighting cell type-specific dysregulation. WGCNA identified two key gene modules (MEyellow and MEtan) that are closely associated with OXPHOS. Three hub genes—<i>LAMTOR2</i>, <i>APBB1IP</i>, and <i>DGKQ</i>—were screened using machine learning methods and validated by RT-PCR and scRNA-seq. Among them, <i>LAMTOR2</i> was significantly more highly expressed in patients with AS, and functional analyses showed that it plays a role in promoting TH17 cell differentiation, which highlights its potential as a therapeutic target for ankylosing spondylitis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>This multi-omics study provides valuable insights into the complex interplay between OXPHOS and AS. The identified genes, particularly <i>LAMTOR2</i>, serve as potential therapeutic targets, contributing to our understanding of AS mechanisms and paving the way for precision medicine in AS treatment.</p>\\n </section>\\n </div>\",\"PeriodicalId\":14330,\"journal\":{\"name\":\"International Journal of Rheumatic Diseases\",\"volume\":\"28 5\",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Rheumatic Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/1756-185X.70175\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Rheumatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/1756-185X.70175","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Oxidative Phosphorylation Pathway in Ankylosing Spondylitis: Multi-Omics Analysis and Machine Learning
Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, characterized by immune microenvironment dysregulation and elevated cytokines like TNF-α and IL-17. Mitochondrial oxidative phosphorylation (OXPHOS), crucial for immune cell function and survival, is implicated in AS pathogenesis. This study explores OXPHOS-related mechanisms in AS, identifies key genes using machine learning, and highlights potential therapeutic targets for precision medicine.
Materials and Methods
Peripheral blood mononuclear cells (PBMCs) bulk transcriptomic and single-cell RNA sequencing (scRNA-seq) data from AS patients were analyzed to investigate the role of the OXPHOS pathway in AS. Weighted gene co-expression network analysis (WGCNA) was performed to identify key gene modules associated with OXPHOS. Machine learning techniques, including support vector machine with recursive feature elimination (SVM-RFE), random forest, and least absolute shrinkage and selection operator (LASSO), were applied to identify significant AS-related genes. Real-time PCR (RT-PCR) was used to quantify gene expression, examine their patterns in specific cell subtypes, and explore their functional implications.
Results
Pathway enrichment analysis identified OXPHOS as a significantly enriched pathway distinguishing AS patients from healthy controls, with high normalized enrichment scores and significant group separation in principal component analysis. ScRNA-seq revealed significantly higher OXPHOS scores in AS patients, especially in dendritic cells (DCs) and monocytes, highlighting cell type-specific dysregulation. WGCNA identified two key gene modules (MEyellow and MEtan) that are closely associated with OXPHOS. Three hub genes—LAMTOR2, APBB1IP, and DGKQ—were screened using machine learning methods and validated by RT-PCR and scRNA-seq. Among them, LAMTOR2 was significantly more highly expressed in patients with AS, and functional analyses showed that it plays a role in promoting TH17 cell differentiation, which highlights its potential as a therapeutic target for ankylosing spondylitis.
Conclusion
This multi-omics study provides valuable insights into the complex interplay between OXPHOS and AS. The identified genes, particularly LAMTOR2, serve as potential therapeutic targets, contributing to our understanding of AS mechanisms and paving the way for precision medicine in AS treatment.
期刊介绍:
The International Journal of Rheumatic Diseases (formerly APLAR Journal of Rheumatology) is the official journal of the Asia Pacific League of Associations for Rheumatology. The Journal accepts original articles on clinical or experimental research pertinent to the rheumatic diseases, work on connective tissue diseases and other immune and allergic disorders. The acceptance criteria for all papers are the quality and originality of the research and its significance to our readership. Except where otherwise stated, manuscripts are peer reviewed by two anonymous reviewers and the Editor.