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Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder

Major depressive disorder (MDD) is a mental illness with high incidence and complex etiology, that poses a serious threat to human health and increases the socioeconomic burden. Currently, high-accuracy biomarkers for MDD diagnosis are urgently needed. This paper aims to identify novel blood-based d...

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Autores principales: Xie, Yinping, Xiao, Ling, Chen, Lijuan, Zheng, Yage, Zhang, Caixia, Wang, Gaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912210/
https://www.ncbi.nlm.nih.gov/pubmed/33513891
http://dx.doi.org/10.3390/genes12020178
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author Xie, Yinping
Xiao, Ling
Chen, Lijuan
Zheng, Yage
Zhang, Caixia
Wang, Gaohua
author_facet Xie, Yinping
Xiao, Ling
Chen, Lijuan
Zheng, Yage
Zhang, Caixia
Wang, Gaohua
author_sort Xie, Yinping
collection PubMed
description Major depressive disorder (MDD) is a mental illness with high incidence and complex etiology, that poses a serious threat to human health and increases the socioeconomic burden. Currently, high-accuracy biomarkers for MDD diagnosis are urgently needed. This paper aims to identify novel blood-based diagnostic biomarkers for MDD. Whole blood DNA methylation data and gene expression data from the Gene Expression Omnibus database are downloaded. Then, differentially expressed/methylated genes (DEGs/DMGs) are identified. In addition, we made a systematic analysis of the DNA methylation on 5′-C-phosphate-G-3′ (CpGs) in all of the gene regions, as well as different gene regions, and then we defined a “dominant” region. Subsequently, integrated analysis is employed to identify the robust MDD-related blood biomarkers. Finally, a gene expression classifier and a methylation classifier are constructed using the random forest algorithm and the leave-one-out cross-validation method. Our results demonstrate that DEGs are mainly involved in the inflammatory response-associated pathways, while DMGs are primarily concentrated in the neurodevelopment- and neuroplasticity-associated pathways. Our integrated analysis identified 46 hypo-methylated and up-regulated (hypo-up) genes and 71 hyper-methylated and down-regulated (hyper-down) genes. One gene expression classifier and two DNA methylation classifiers, based on the CpGs in all of the regions or in the dominant regions are constructed. The gene expression classifier possessed the best predictive ability, followed by the DNA methylation classifiers, based on the CpGs in both the dominant regions and all of the regions. In summary, the integrated analysis of DNA methylation and gene expression has identified 46 hypo-up genes and 71 hyper-down genes, which could be used as diagnostic biomarkers for MDD.
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spelling pubmed-79122102021-02-28 Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder Xie, Yinping Xiao, Ling Chen, Lijuan Zheng, Yage Zhang, Caixia Wang, Gaohua Genes (Basel) Article Major depressive disorder (MDD) is a mental illness with high incidence and complex etiology, that poses a serious threat to human health and increases the socioeconomic burden. Currently, high-accuracy biomarkers for MDD diagnosis are urgently needed. This paper aims to identify novel blood-based diagnostic biomarkers for MDD. Whole blood DNA methylation data and gene expression data from the Gene Expression Omnibus database are downloaded. Then, differentially expressed/methylated genes (DEGs/DMGs) are identified. In addition, we made a systematic analysis of the DNA methylation on 5′-C-phosphate-G-3′ (CpGs) in all of the gene regions, as well as different gene regions, and then we defined a “dominant” region. Subsequently, integrated analysis is employed to identify the robust MDD-related blood biomarkers. Finally, a gene expression classifier and a methylation classifier are constructed using the random forest algorithm and the leave-one-out cross-validation method. Our results demonstrate that DEGs are mainly involved in the inflammatory response-associated pathways, while DMGs are primarily concentrated in the neurodevelopment- and neuroplasticity-associated pathways. Our integrated analysis identified 46 hypo-methylated and up-regulated (hypo-up) genes and 71 hyper-methylated and down-regulated (hyper-down) genes. One gene expression classifier and two DNA methylation classifiers, based on the CpGs in all of the regions or in the dominant regions are constructed. The gene expression classifier possessed the best predictive ability, followed by the DNA methylation classifiers, based on the CpGs in both the dominant regions and all of the regions. In summary, the integrated analysis of DNA methylation and gene expression has identified 46 hypo-up genes and 71 hyper-down genes, which could be used as diagnostic biomarkers for MDD. MDPI 2021-01-27 /pmc/articles/PMC7912210/ /pubmed/33513891 http://dx.doi.org/10.3390/genes12020178 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xie, Yinping
Xiao, Ling
Chen, Lijuan
Zheng, Yage
Zhang, Caixia
Wang, Gaohua
Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder
title Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder
title_full Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder
title_fullStr Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder
title_full_unstemmed Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder
title_short Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder
title_sort integrated analysis of methylomic and transcriptomic data to identify potential diagnostic biomarkers for major depressive disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912210/
https://www.ncbi.nlm.nih.gov/pubmed/33513891
http://dx.doi.org/10.3390/genes12020178
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