Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning
Yang Zhang,1– 4 Yang Hai,1– 3 Bangguo Song,4 Jing Xu,1– 3 Liangjia Cao,5 Rukeye Yasen,5 Wenjuan Xu,5 Jiaxuan Zhang,5 Jihong Hu6 1Scientific Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 2Key Laboratory of Dunhuang Medicine, Ministry of E...
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Dove Medical Press
2025-02-01
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| author | Zhang Y Hai Y Song B Xu J Cao L Yasen R Xu W Zhang J Hu J |
| author_facet | Zhang Y Hai Y Song B Xu J Cao L Yasen R Xu W Zhang J Hu J |
| author_sort | Zhang Y |
| collection | DOAJ |
| description | Yang Zhang,1– 4 Yang Hai,1– 3 Bangguo Song,4 Jing Xu,1– 3 Liangjia Cao,5 Rukeye Yasen,5 Wenjuan Xu,5 Jiaxuan Zhang,5 Jihong Hu6 1Scientific Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 2Key Laboratory of Dunhuang Medicine, Ministry of Education, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 3Research Center of Traditional Chinese Medicine, Gansu Province, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 4Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 5College of Public Health, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 6Laboratory and Simulation Training Center, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaCorrespondence: Jihong Hu, Laboratory and Simulation Training Center, Gansu University of Chinese Medicine, Chengguan District, Lanzhou, Gansu, 73000, People’s Republic of China, Email hujihonghappy@163.comPurpose: Asthma is one of the most common chronic respiratory diseases affecting children, and there is currently no clear remedy. Immune cells play a key role in childhood asthma. Therefore, a deeper investigation of the correlation between immune cells and childhood asthma could lead to a better understanding of asthma’s origin, the identification of potential treatment targets, and the development of personalized treatment strategies.Patients and Methods: We used a two-sample Mendelian randomization (MR) analysis to investigate the possible causal relationship between childhood asthma and a total of 731 immune cells, including B cell (190), Maturation stages of T cell (79), Monocyte (43), Myeloid cell (64), TBNK (124), Treg (167), and CDC (64). LASSO logistic regression and SVM algorithms were used to identify key genes associated with childhood asthma. Specific signaling pathways associated with these key genes were further explored through gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Subsequently, the four key genes FCGR3A, TCTN3, ALOX5, and IL4R were verified in an established asthma mouse model using quantitative real-time PCR and Western blotting.Results: MR analysis showed that 60 immune cells were associated with childhood asthma, of which 32 were associated with high risk and 28 were associated with low risk. LASSO logistic regression and SVM algorithm identified six key genes that affect childhood asthma as ATF4, FCGR3A, GAS5, MGAT3, TAB1, and TCTN3. In addition, four genes, FCGR3A, TCTN3, ALOX5, and IL4R, were verified through animal experiments.Conclusion: Our findings confirmed that immune cells contribute to childhood asthma, highlighting the importance of key genes in the role of the immune microenvironment in this disease. These insights provide a new path for the exploration of the biological underpinnings of childhood asthma and the development of early intervention therapies.Keywords: childhood asthma, immune cells, Mendelian randomization, biomarker, key genes |
| format | Article |
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| institution | OA Journals |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
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| series | Journal of Inflammation Research |
| spelling | doaj-art-d5bd37fbe6fb4db2b5ce01a58b3877e82025-08-20T02:14:31ZengDove Medical PressJournal of Inflammation Research1178-70312025-02-01Volume 1825832600100407Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine LearningZhang YHai YSong BXu JCao LYasen RXu WZhang JHu JYang Zhang,1– 4 Yang Hai,1– 3 Bangguo Song,4 Jing Xu,1– 3 Liangjia Cao,5 Rukeye Yasen,5 Wenjuan Xu,5 Jiaxuan Zhang,5 Jihong Hu6 1Scientific Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 2Key Laboratory of Dunhuang Medicine, Ministry of Education, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 3Research Center of Traditional Chinese Medicine, Gansu Province, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 4Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 5College of Public Health, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 6Laboratory and Simulation Training Center, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaCorrespondence: Jihong Hu, Laboratory and Simulation Training Center, Gansu University of Chinese Medicine, Chengguan District, Lanzhou, Gansu, 73000, People’s Republic of China, Email hujihonghappy@163.comPurpose: Asthma is one of the most common chronic respiratory diseases affecting children, and there is currently no clear remedy. Immune cells play a key role in childhood asthma. Therefore, a deeper investigation of the correlation between immune cells and childhood asthma could lead to a better understanding of asthma’s origin, the identification of potential treatment targets, and the development of personalized treatment strategies.Patients and Methods: We used a two-sample Mendelian randomization (MR) analysis to investigate the possible causal relationship between childhood asthma and a total of 731 immune cells, including B cell (190), Maturation stages of T cell (79), Monocyte (43), Myeloid cell (64), TBNK (124), Treg (167), and CDC (64). LASSO logistic regression and SVM algorithms were used to identify key genes associated with childhood asthma. Specific signaling pathways associated with these key genes were further explored through gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Subsequently, the four key genes FCGR3A, TCTN3, ALOX5, and IL4R were verified in an established asthma mouse model using quantitative real-time PCR and Western blotting.Results: MR analysis showed that 60 immune cells were associated with childhood asthma, of which 32 were associated with high risk and 28 were associated with low risk. LASSO logistic regression and SVM algorithm identified six key genes that affect childhood asthma as ATF4, FCGR3A, GAS5, MGAT3, TAB1, and TCTN3. In addition, four genes, FCGR3A, TCTN3, ALOX5, and IL4R, were verified through animal experiments.Conclusion: Our findings confirmed that immune cells contribute to childhood asthma, highlighting the importance of key genes in the role of the immune microenvironment in this disease. These insights provide a new path for the exploration of the biological underpinnings of childhood asthma and the development of early intervention therapies.Keywords: childhood asthma, immune cells, Mendelian randomization, biomarker, key geneshttps://www.dovepress.com/screening-and-validation-of-potential-biomarkers-of-immune-cells-in-ch-peer-reviewed-fulltext-article-JIRchildhood asthmaimmune cellsmendelian randomizationbiomarkerkey genes |
| spellingShingle | Zhang Y Hai Y Song B Xu J Cao L Yasen R Xu W Zhang J Hu J Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning Journal of Inflammation Research childhood asthma immune cells mendelian randomization biomarker key genes |
| title | Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning |
| title_full | Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning |
| title_fullStr | Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning |
| title_full_unstemmed | Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning |
| title_short | Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning |
| title_sort | screening and validation of potential biomarkers of immune cells in childhood asthma patients via mendelian randomization and machine learning |
| topic | childhood asthma immune cells mendelian randomization biomarker key genes |
| url | https://www.dovepress.com/screening-and-validation-of-potential-biomarkers-of-immune-cells-in-ch-peer-reviewed-fulltext-article-JIR |
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