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Zhaoyu LIU


Jingfeng WANG


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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.9 P.718-732


Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke

Author(s):  Chiyu LIU, Sixu CHEN, Haifeng ZHANG, Yangxin CHEN, Qingyuan GAO, Zhiteng CHEN, Zhaoyu LIU, Jingfeng WANG

Affiliation(s):  Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; more

Corresponding email(s):   liuzhy98@mail.sysu.edu.cn, dr_wjf@vip.163.com

Key Words:  Cardioembolic stroke, Heart failure, Bioinformatics, Weighted gene co-expression network analysis (WGCNA)

Chiyu LIU, Sixu CHEN, Haifeng ZHANG, Yangxin CHEN, Qingyuan GAO, Zhiteng CHEN, Zhaoyu LIU, Jingfeng WANG. Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke[J]. Journal of Zhejiang University Science B, 2021, 22(9): 718-732.

@article{title="Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke",
author="Chiyu LIU, Sixu CHEN, Haifeng ZHANG, Yangxin CHEN, Qingyuan GAO, Zhiteng CHEN, Zhaoyu LIU, Jingfeng WANG",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke
%A Chiyu LIU
%A Sixu CHEN
%A Haifeng ZHANG
%A Yangxin CHEN
%A Qingyuan GAO
%A Zhiteng CHEN
%A Zhaoyu LIU
%A Jingfeng WANG
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 9
%P 718-732
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000544

T1 - Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke
A1 - Chiyu LIU
A1 - Sixu CHEN
A1 - Haifeng ZHANG
A1 - Yangxin CHEN
A1 - Qingyuan GAO
A1 - Zhiteng CHEN
A1 - Zhaoyu LIU
A1 - Jingfeng WANG
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 9
SP - 718
EP - 732
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000544

This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure (HF)-related stroke. HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus (GEO) database. weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes. Gene Ontology (GO) and pathway enrichment analyses were performed on genes in the key modules. Genes in HF- and stroke-related key modules were intersected to obtain common genes for HF-related stroke, which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke. Key genes were functionally annotated through GO in the Reactome and Cytoscape databases. Finally, key genes were validated in these two datasets and other datasets. HF- and stroke-related datasets each identified two key modules. Functional enrichment analysis indicated that protein ubiquitination, Wnt signaling, and exosomes were involved in both HF- and stroke-related key modules. Additionally, ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke. OTU deubiquitinase with linear linkage specificity (OTULIN) and nuclear factor interleukin 3-regulated (NFIL3) were determined to be the key genes in HF-related stroke. Through functional annotation, OTULIN was involved in protein ubiquitination and Wnt signaling, and NFIL3 was involved in DNA binding and transcription. Importantly, OTULIN and NFIL3 were also validated to be differentially expressed in all HF and stroke groups. Protein ubiquitination, Wnt signaling, and exosomes were involved in HF-related stroke. OTULIN and NFIL3 may play a key role in HF-related stroke through regulating these processes, and thus serve as promising intervention targets.


目的:本研究通过加权基因共表达网络分析(Weighted gene co-expression network analysis,WGCNA)揭示心力衰竭(心衰)相关脑卒中的发病机制,为临床防治心衰相关脑卒中提供关键靶点。
方法:我们从基因表达综合数据库(Gene Expression Omnibus database,GEO)中分别获得心衰和脑卒中相关的芯片数据,并通过WGCNA鉴定各自的关键模块与关键基因。然后我们将二者的关键模块与关键基因取交集后,得到心衰相关脑卒中的关键基因,并利用Reactome和Cytoscape数据库对关键基因进行功能注释。最后在多个数据集中对心衰相关脑卒中的关键基因进行验证。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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