Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data

Cardiovascular and cerebrovascular diseases are leading causes of death worldwide, accounting for more than 40% of all deaths in China. Acute myocardial infarction (AMI) is a common cardiovascular disease and traditionally divided into ST-segment (STEMI) and non-ST-segment elevation myocardial infar...

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Autores principales:	Jiaxin Luo, Lin Wu, Dinghui Liu, Zhaojun Xiong, Linli Wang, Xiaoxian Qian, Xiaoqiang Sun
Formato:	article
Lenguaje:	EN
Publicado:	AIMS Press 2021
Materias:	acute myocardial infarction multilayer network single-cell rna-seq data network analysis Biotechnology TP248.13-248.65 Mathematics QA1-939
Acceso en línea:	https://doaj.org/article/9c21982adcb94849ad4298b96c9bb0fe
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spelling	oai:doaj.org-article:9c21982adcb94849ad4298b96c9bb0fe2021-11-23T02:45:53ZGene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data10.3934/mbe.20213861551-0018https://doaj.org/article/9c21982adcb94849ad4298b96c9bb0fe2021-09-01T00:00:00Zhttps://www.aimspress.com/article/doi/10.3934/mbe.2021386?viewType=HTMLhttps://doaj.org/toc/1551-0018Cardiovascular and cerebrovascular diseases are leading causes of death worldwide, accounting for more than 40% of all deaths in China. Acute myocardial infarction (AMI) is a common cardiovascular disease and traditionally divided into ST-segment (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), which are known with different prognoses and treatment strategies. However, key regulatory genes and pathways involved in AMI that may be used as potential biomarker for prognosis are unknown. In this study, we employed both bulk and single-cell RNA-seq to construct gene regulatory networks and cell-cell communication networks. We first constructed weighted gene co-expression networks for differential expressed genes between STEMI and NSTEMI patients based on whole-blood RNA-seq transcriptomics. Network topological attributes (e.g., node degree, betweenness) were analyzed to identify key genes involved in different functional network modules. Furthermore, we used single-cell RNA-seq data to construct multilayer signaling network to infer regulatory mechanisms of the above key genes. PLAUR (receptor for urokinase plasminogen activator) was found to play a vital role in transducing inter-cellular signals from endothelial cells and fibroblast cells to intra-cellular pathways of myocardial cells, leading to gene expression involved in cellular response to hypoxia. Our study sheds lights on identifying molecular biomarkers for diagnosis and prognosis of AMI, and provides candidate key regulatory genes for further experimental validation.Jiaxin LuoLin WuDinghui Liu Zhaojun XiongLinli WangXiaoxian Qian Xiaoqiang SunAIMS Pressarticleacute myocardial infarctionmultilayer networksingle-cell rna-seq datanetwork analysisBiotechnologyTP248.13-248.65MathematicsQA1-939ENMathematical Biosciences and Engineering, Vol 18, Iss 6, Pp 7774-7789 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute myocardial infarction multilayer network single-cell rna-seq data network analysis Biotechnology TP248.13-248.65 Mathematics QA1-939
spellingShingle	acute myocardial infarction multilayer network single-cell rna-seq data network analysis Biotechnology TP248.13-248.65 Mathematics QA1-939 Jiaxin Luo Lin Wu Dinghui Liu Zhaojun Xiong Linli Wang Xiaoxian Qian Xiaoqiang Sun Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data
description	Cardiovascular and cerebrovascular diseases are leading causes of death worldwide, accounting for more than 40% of all deaths in China. Acute myocardial infarction (AMI) is a common cardiovascular disease and traditionally divided into ST-segment (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), which are known with different prognoses and treatment strategies. However, key regulatory genes and pathways involved in AMI that may be used as potential biomarker for prognosis are unknown. In this study, we employed both bulk and single-cell RNA-seq to construct gene regulatory networks and cell-cell communication networks. We first constructed weighted gene co-expression networks for differential expressed genes between STEMI and NSTEMI patients based on whole-blood RNA-seq transcriptomics. Network topological attributes (e.g., node degree, betweenness) were analyzed to identify key genes involved in different functional network modules. Furthermore, we used single-cell RNA-seq data to construct multilayer signaling network to infer regulatory mechanisms of the above key genes. PLAUR (receptor for urokinase plasminogen activator) was found to play a vital role in transducing inter-cellular signals from endothelial cells and fibroblast cells to intra-cellular pathways of myocardial cells, leading to gene expression involved in cellular response to hypoxia. Our study sheds lights on identifying molecular biomarkers for diagnosis and prognosis of AMI, and provides candidate key regulatory genes for further experimental validation.
format	article
author	Jiaxin Luo Lin Wu Dinghui Liu Zhaojun Xiong Linli Wang Xiaoxian Qian Xiaoqiang Sun
author_facet	Jiaxin Luo Lin Wu Dinghui Liu Zhaojun Xiong Linli Wang Xiaoxian Qian Xiaoqiang Sun
author_sort	Jiaxin Luo
title	Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data
title_short	Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data
title_full	Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data
title_fullStr	Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data
title_full_unstemmed	Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data
title_sort	gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell rna-seq data
publisher	AIMS Press
publishDate	2021
url	https://doaj.org/article/9c21982adcb94849ad4298b96c9bb0fe
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_version_	1718417391972515840

Gene regulatory network analysis identifies key genes and regulatory mechanisms involved in acute myocardial infarction using bulk and single cell RNA-seq data

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