Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis

ObjectiveThis study aimed to identify candidate gene biomarkers associated with immune infiltration in idiopathic pulmonary fibrosis (IPF) based on machine learning algorithms.MethodsMicroarray datasets of IPF were extracted from the Gene Expression Omnibus (GEO) database to screen for differentiall...

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Main Authors: Yufeng Zhang, Cong Wang, Qingqing Xia, Weilong Jiang, Huizhe Zhang, Ehsan Amiri-Ardekani, Haibing Hua, Yi Cheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2023.1001813/full
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author Yufeng Zhang
Cong Wang
Qingqing Xia
Weilong Jiang
Huizhe Zhang
Ehsan Amiri-Ardekani
Haibing Hua
Yi Cheng
author_facet Yufeng Zhang
Cong Wang
Qingqing Xia
Weilong Jiang
Huizhe Zhang
Ehsan Amiri-Ardekani
Haibing Hua
Yi Cheng
author_sort Yufeng Zhang
collection DOAJ
description ObjectiveThis study aimed to identify candidate gene biomarkers associated with immune infiltration in idiopathic pulmonary fibrosis (IPF) based on machine learning algorithms.MethodsMicroarray datasets of IPF were extracted from the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes (DEGs). The DEGs were subjected to enrichment analysis, and two machine learning algorithms were used to identify candidate genes associated with IPF. These genes were verified in a validation cohort from the GEO database. Receiver operating characteristic (ROC) curves were plotted to assess the predictive value of the IPF-associated genes. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was used to evaluate the proportion of immune cells in IPF and normal tissues. Additionally, the correlation between the expression of IPF-associated genes and the infiltration levels of immune cells was examined.ResultsA total of 302 upregulated and 192 downregulated genes were identified. Functional annotation, pathway enrichment, Disease Ontology and gene set enrichment analyses revealed that the DEGs were related to the extracellular matrix and immune responses. COL3A1, CDH3, CEBPD, and GPIHBP1 were identified as candidate biomarkers using machine learning algorithms, and their predictive value was verified in a validation cohort. Additionally, ROC analysis revealed that the four genes had high predictive accuracy. The infiltration levels of plasma cells, M0 macrophages and resting dendritic cells were higher and those of resting natural killer (NK) cells, M1 macrophages and eosinophils were lower in the lung tissues of patients with IPF than in those of healthy individuals. The expression of the abovementioned genes was correlated with the infiltration levels of plasma cells, M0 macrophages and eosinophils.ConclusionCOL3A1, CDH3, CEBPD, and GPIHBP1 are candidate biomarkers of IPF. Plasma cells, M0 macrophages and eosinophils may be involved in the development of IPF and may serve as immunotherapeutic targets in IPF.
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spelling doaj.art-2d12f7e58e694d089c74316153db9b4a2023-02-13T05:35:57ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-02-011010.3389/fmed.2023.10018131001813Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosisYufeng Zhang0Cong Wang1Qingqing Xia2Weilong Jiang3Huizhe Zhang4Ehsan Amiri-Ardekani5Haibing Hua6Yi Cheng7Department of Pulmonary and Critical Care Medicine, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, Jiangsu, ChinaDepartment of Pulmonary and Critical Care Medicine, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, Jiangsu, ChinaDepartment of Pulmonary and Critical Care Medicine, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, Jiangsu, ChinaDepartment of Pulmonary and Critical Care Medicine, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, Jiangsu, ChinaDepartment of Respiratory Medicine, Yancheng Hospital of Traditional Chinese Medicine, Yancheng Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu, ChinaDepartment of Phytopharmaceuticals (Traditional Pharmacy), Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Gastroenterology, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, Jiangsu, ChinaDepartment of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaObjectiveThis study aimed to identify candidate gene biomarkers associated with immune infiltration in idiopathic pulmonary fibrosis (IPF) based on machine learning algorithms.MethodsMicroarray datasets of IPF were extracted from the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes (DEGs). The DEGs were subjected to enrichment analysis, and two machine learning algorithms were used to identify candidate genes associated with IPF. These genes were verified in a validation cohort from the GEO database. Receiver operating characteristic (ROC) curves were plotted to assess the predictive value of the IPF-associated genes. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was used to evaluate the proportion of immune cells in IPF and normal tissues. Additionally, the correlation between the expression of IPF-associated genes and the infiltration levels of immune cells was examined.ResultsA total of 302 upregulated and 192 downregulated genes were identified. Functional annotation, pathway enrichment, Disease Ontology and gene set enrichment analyses revealed that the DEGs were related to the extracellular matrix and immune responses. COL3A1, CDH3, CEBPD, and GPIHBP1 were identified as candidate biomarkers using machine learning algorithms, and their predictive value was verified in a validation cohort. Additionally, ROC analysis revealed that the four genes had high predictive accuracy. The infiltration levels of plasma cells, M0 macrophages and resting dendritic cells were higher and those of resting natural killer (NK) cells, M1 macrophages and eosinophils were lower in the lung tissues of patients with IPF than in those of healthy individuals. The expression of the abovementioned genes was correlated with the infiltration levels of plasma cells, M0 macrophages and eosinophils.ConclusionCOL3A1, CDH3, CEBPD, and GPIHBP1 are candidate biomarkers of IPF. Plasma cells, M0 macrophages and eosinophils may be involved in the development of IPF and may serve as immunotherapeutic targets in IPF.https://www.frontiersin.org/articles/10.3389/fmed.2023.1001813/fullgene biomarkerimmune infiltrationidiopathic pulmonary fibrosismachine learning algorithmCIBERSORT
spellingShingle Yufeng Zhang
Cong Wang
Qingqing Xia
Weilong Jiang
Huizhe Zhang
Ehsan Amiri-Ardekani
Haibing Hua
Yi Cheng
Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis
Frontiers in Medicine
gene biomarker
immune infiltration
idiopathic pulmonary fibrosis
machine learning algorithm
CIBERSORT
title Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis
title_full Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis
title_fullStr Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis
title_full_unstemmed Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis
title_short Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis
title_sort machine learning based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis
topic gene biomarker
immune infiltration
idiopathic pulmonary fibrosis
machine learning algorithm
CIBERSORT
url https://www.frontiersin.org/articles/10.3389/fmed.2023.1001813/full
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