Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy

Autor: Jianjiao Mo, Xingshou Pan, Yan Liu, Wei Yan, Zhaohe Huang, Xiannan Huang, Liufang Zhou, Li Liu, Meidan Huang, Zhen Zhang, Chengcai Chen, Jianjun Huang, Zhile Li, Baomin Wei, Zhuohua Zhang, Tengfang Lai, Fengzhen He, Qinjiang Wei
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Cardiomyopathy
Dilated
Male
0301 basic medicine
Article Subject
Protein digestion
Heart Ventricles
Computational biology
030204 cardiovascular system & hematology
Biology
Gene mutation
medicine.disease_cause
Polymorphism
Single Nucleotide
Genome
complex mixtures
General Biochemistry
Genetics and Molecular Biology
Transcriptome
Epigenome
03 medical and health sciences
0302 clinical medicine
Exome Sequencing
medicine
Humans
Protein Interaction Maps
cardiovascular diseases
Gene
Exome sequencing
Mutation
General Immunology and Microbiology
Genome
Human
Gene Expression Profiling
Reproducibility of Results
Molecular Sequence Annotation
Genomics
General Medicine
DNA Methylation
Middle Aged
musculoskeletal system
Gene Ontology
030104 developmental biology
cardiovascular system
Medicine
Female
Research Article
Zdroj: BioMed Research International, Vol 2021 (2021)
BioMed Research International
ISSN: 2314-6141
2314-6133
Popis: Objective. Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods. Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results. 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 ( degree = 24 ), GNB3 ( degree = 23 ), QSOX1 ( degree = 21 ), and APOB ( degree = 17 ). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion. Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.
Databáze: OpenAIRE
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