Identification of potential dilated cardiomyopathy-related targets by meta-analysis and co-expression analysis of human RNA-sequencing datasets

Dilated cardiomyopathy (DCM) remains among the most refractory heart diseases because of its complicated pathogenesis, and the key molecules that cause it remain unclear. To elucidate the molecules and upstream pathways critical for DCM pathogenesis, we performed meta-analysis and co-expression anal...

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Published in:Life sciences (1973) 2022-10, Vol.306, p.120807-120807, Article 120807
Main Authors: Yuan, Zixun, Murakoshi, Nobuyuki, Xu, Dongzhu, Tajiri, Kazuko, Okabe, Yuta, Aonuma, Kazuhiro, Murakata, Yoshiko, Li, Siqi, Song, Zonghu, Shimoda, Yuzuno, Mori, Haruka, Aonuma, Kazutaka, Ieda, Masaki
Format: Article
Language:English
Subjects:
cardiomyopathy
Co-expression network
data collection
Dilated cardiomyopathy
gene expression regulation
genes
heart
heart failure
Hub gene
humans
meta-analysis
pathogenesis
protein-protein interactions
RNA
RNA-seq
sequence analysis
transcription (genetics)
Transcriptional regulator
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container_title Life sciences (1973)
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creator Yuan, Zixun
Murakoshi, Nobuyuki
Xu, Dongzhu
Tajiri, Kazuko
Okabe, Yuta
Aonuma, Kazuhiro
Murakata, Yoshiko
Li, Siqi
Song, Zonghu
Shimoda, Yuzuno
Mori, Haruka
Aonuma, Kazutaka
Ieda, Masaki
description Dilated cardiomyopathy (DCM) remains among the most refractory heart diseases because of its complicated pathogenesis, and the key molecules that cause it remain unclear. To elucidate the molecules and upstream pathways critical for DCM pathogenesis, we performed meta-analysis and co-expression analysis of RNA-sequencing (RNA-seq) datasets from publicly available databases. We analyzed three RNA-seq datasets containing comparisons of RNA expression in left ventricles between healthy controls and DCM patients. We extracted differentially expressed genes (DEGs) and clarified upstream regulators of cardiovascular disease-related DEGs by Ingenuity Pathway Analysis (IPA). Weighted Gene Co-expression Network Analysis (WGCNA) and Protein–Protein Interaction (PPI) analysis were also used to identify the hub gene candidates strongly associated with DCM. In total, 406 samples (184 healthy, 222 DCM) were used in this study. Overall, 391 DEGs [absolute fold change (FC) ≥ 1.5; P 
doi_str_mv 10.1016/j.lfs.2022.120807
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To elucidate the molecules and upstream pathways critical for DCM pathogenesis, we performed meta-analysis and co-expression analysis of RNA-sequencing (RNA-seq) datasets from publicly available databases. We analyzed three RNA-seq datasets containing comparisons of RNA expression in left ventricles between healthy controls and DCM patients. We extracted differentially expressed genes (DEGs) and clarified upstream regulators of cardiovascular disease-related DEGs by Ingenuity Pathway Analysis (IPA). Weighted Gene Co-expression Network Analysis (WGCNA) and Protein–Protein Interaction (PPI) analysis were also used to identify the hub gene candidates strongly associated with DCM. In total, 406 samples (184 healthy, 222 DCM) were used in this study. Overall, 391 DEGs [absolute fold change (FC) ≥ 1.5; P &lt; 0.01], including 221 upregulated and 170 downregulated ones in DCM, were extracted. Seven common hub genes (LUM, COL1A2, CXCL10, FMOD, COL3A1, ADAMTS4, MRC1) were finally screened. IPA showed several upstream transcriptional regulators, including activating (NFKBIA, TP73, CALR, NFKB1, KLF4) and inhibiting (CEBPA, PPARGC1A) ones. We further validated increased expression of several common hub genes in the transverse aortic constriction-induced heart failure model. 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IPA showed several upstream transcriptional regulators, including activating (NFKBIA, TP73, CALR, NFKB1, KLF4) and inhibiting (CEBPA, PPARGC1A) ones. We further validated increased expression of several common hub genes in the transverse aortic constriction-induced heart failure model. 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IPA showed several upstream transcriptional regulators, including activating (NFKBIA, TP73, CALR, NFKB1, KLF4) and inhibiting (CEBPA, PPARGC1A) ones. We further validated increased expression of several common hub genes in the transverse aortic constriction-induced heart failure model. In conclusion, meta-analysis and WGCNA using RNA-seq databases of DCM patients identified seven hub genes and seven upstream transcriptional regulators.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.lfs.2022.120807</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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source ScienceDirect Journals
subjects cardiomyopathy
Co-expression network
data collection
Dilated cardiomyopathy
gene expression regulation
genes
heart
heart failure
Hub gene
humans
meta-analysis
pathogenesis
protein-protein interactions
RNA
RNA-seq
sequence analysis
transcription (genetics)
Transcriptional regulator
title Identification of potential dilated cardiomyopathy-related targets by meta-analysis and co-expression analysis of human RNA-sequencing datasets
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