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

Jiaxin Luo; Lin Wu; Dinghui Liu; Zhaojun Xiong; Linli Wang; Xiaoxian Qian; Xiaoqiang Sun; Jiaxin Luo; Lin Wu; Dinghui Liu; Zhaojun Xiong; Linli Wang; Xiaoxian Qian; Xiaoqiang Sun

doi:10.3934/mbe.2021386

Mathematical Biosciences and Engineering

2021, Volume 18, Issue 6: 7774-7789. doi: 10.3934/mbe.2021386

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

1.
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
2.
Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
3.
School of Mathematics, Sun Yat-sen University, Guangzhou 510275, China
^† These authors contributed equally to this study and are co-first authors.

Received: 26 August 2021 Accepted: 06 September 2021 Published: 09 September 2021

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.
- acute myocardial infarction,
- multilayer network,
- Single-cell RNA-seq data,
- network analysis
Citation: 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[J]. Mathematical Biosciences and Engineering, 2021, 18(6): 7774-7789. doi: 10.3934/mbe.2021386

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Abstract

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.

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