Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis

Drug-induced liver injury (DILI) is the most common adverse effect of numerous drugs and a leading cause of drug withdrawal from the market. In recent years, the incidence of DILI has increased. However, diagnosing DILI remains challenging because of the lack of specific biomarkers. Hence, we used m...

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Main Authors: Kaiyue Wang, Lin Zhang, Lixia Li, Yi Wang, Xinqin Zhong, Chunyu Hou, Yuqi Zhang, Congying Sun, Qian Zhou, Xiaoying Wang
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/19/11945
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author Kaiyue Wang
Lin Zhang
Lixia Li
Yi Wang
Xinqin Zhong
Chunyu Hou
Yuqi Zhang
Congying Sun
Qian Zhou
Xiaoying Wang
author_facet Kaiyue Wang
Lin Zhang
Lixia Li
Yi Wang
Xinqin Zhong
Chunyu Hou
Yuqi Zhang
Congying Sun
Qian Zhou
Xiaoying Wang
author_sort Kaiyue Wang
collection DOAJ
description Drug-induced liver injury (DILI) is the most common adverse effect of numerous drugs and a leading cause of drug withdrawal from the market. In recent years, the incidence of DILI has increased. However, diagnosing DILI remains challenging because of the lack of specific biomarkers. Hence, we used machine learning (ML) to mine multiple microarrays and identify useful genes that could contribute to diagnosing DILI. In this prospective study, we screened six eligible microarrays from the Gene Expression Omnibus (GEO) database. First, 21 differentially expressed genes (DEGs) were identified in the training set. Subsequently, a functional enrichment analysis of the DEGs was performed. We then used six ML algorithms to identify potentially useful genes. Based on receiver operating characteristic (ROC), four genes, DDIT3, GADD45A, SLC3A2, and RBM24, were identified. The average values of the area under the curve (AUC) for these four genes were higher than 0.8 in both the training and testing sets. In addition, the results of immune cell correlation analysis showed that these four genes were highly significantly correlated with multiple immune cells. Our study revealed that DDIT3, GADD45A, SLC3A2, and RBM24 could be biomarkers contributing to the identification of patients with DILI.
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spelling doaj.art-266a457c434c49ac928c5973436f64e82023-11-23T20:41:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191194510.3390/ijms231911945Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics AnalysisKaiyue Wang0Lin Zhang1Lixia Li2Yi Wang3Xinqin Zhong4Chunyu Hou5Yuqi Zhang6Congying Sun7Qian Zhou8Xiaoying Wang9Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaCollege of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaDrug-induced liver injury (DILI) is the most common adverse effect of numerous drugs and a leading cause of drug withdrawal from the market. In recent years, the incidence of DILI has increased. However, diagnosing DILI remains challenging because of the lack of specific biomarkers. Hence, we used machine learning (ML) to mine multiple microarrays and identify useful genes that could contribute to diagnosing DILI. In this prospective study, we screened six eligible microarrays from the Gene Expression Omnibus (GEO) database. First, 21 differentially expressed genes (DEGs) were identified in the training set. Subsequently, a functional enrichment analysis of the DEGs was performed. We then used six ML algorithms to identify potentially useful genes. Based on receiver operating characteristic (ROC), four genes, DDIT3, GADD45A, SLC3A2, and RBM24, were identified. The average values of the area under the curve (AUC) for these four genes were higher than 0.8 in both the training and testing sets. In addition, the results of immune cell correlation analysis showed that these four genes were highly significantly correlated with multiple immune cells. Our study revealed that DDIT3, GADD45A, SLC3A2, and RBM24 could be biomarkers contributing to the identification of patients with DILI.https://www.mdpi.com/1422-0067/23/19/11945drug-induced liver injurymachine learningdiagnosisbiomarkermultiple microarrays
spellingShingle Kaiyue Wang
Lin Zhang
Lixia Li
Yi Wang
Xinqin Zhong
Chunyu Hou
Yuqi Zhang
Congying Sun
Qian Zhou
Xiaoying Wang
Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis
International Journal of Molecular Sciences
drug-induced liver injury
machine learning
diagnosis
biomarker
multiple microarrays
title Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis
title_full Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis
title_fullStr Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis
title_full_unstemmed Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis
title_short Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis
title_sort identification of drug induced liver injury biomarkers from multiple microarrays based on machine learning and bioinformatics analysis
topic drug-induced liver injury
machine learning
diagnosis
biomarker
multiple microarrays
url https://www.mdpi.com/1422-0067/23/19/11945
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