The Joint Analysis of Multi-Omics Data Revealed the Methylation-Expression Regulations in Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is one of the most prevalent heart rhythm disorder. The causes of AF include age, male sex, diabetes, hypertension, valve disease, and systolic/diastolic dysfunction. But on molecular level, its mechanisms are largely unknown. In this study, we collected 10 patients with persistent atrial fibrillation, 10 patients with paroxymal atrial fibrillation and 10 healthy individuals and did Methylation EPICBead Chip and RNA sequencing. By analyzing the methylation and gene expression data using machine learning based feature selection method Boruta, we identified the key genes that were strongly associated with AF and found their interconnections. The results suggested that the methylation of KIF15 may regulate the expression of PSMC3, TINAG, and NUDT6. The identified AF associated methylation-expression regulations may help understand the molecular mechanisms of AF from a multi-omics perspective.

[Retracted] Multiomics Analysis of Genetics and Epigenetics Reveals Pathogenesis and Therapeutic Targets for Atrial Fibrillation

“…As a result, we identified 28 differentially expressed and methylated genes for AF. As a recent study, Liu et al identified abnormally expressed PSMC3, TINAG, and NUDT regulated by methylation for AF [ 5 ]. Among 28 differentially expressed and methylated genes, 5 have been reported to be related with AF.…”

“…With the development of next-generation sequencing (NGS) technology, abnormally expressed genes have been shown to be involved in the pathogenesis of AF [ 4 ]. DNA methylation, as one of the main epigenetic modifications, has been confirmed to be related to pathogenesis of AF [ 5 ]. DNA methylation occurs at the global and specific gene promoter level.…”

“…Nevertheless, these genes only partially explain the biological and genetic basis of AF. Only one study identified abnormally expressed genes (PSMC3, TINAG, and NUDT) regulated by methylation for AF based on multiomics analysis [ 5 ]. Herein, our study is aimed at comprehensively analyzing the genetics and epigenetics of AF, which could provide a new insight into underlying molecular mechanisms and provide therapeutic targets for AF.…”

Genetics and Epigenetics of Atrial Fibrillation

“…Emelia’s lab has identified two CpG sites significantly associated with prevalent AF, and five CpGs associated with incident AF, and fourteen previously reported genome-wide significant AF-related SNP were each associated with at least one CpG site; being the most significant association rs6490029 at the CUX2 locus and cg10833066 [ 208 ]. Recently studies have shown that KIF15 methylation may play important role in the pathogenesis of AF through the regulation of the expression of proteasome 26S subunit ATPase 3 ( PSMC3 ), tubulointerstitial nephritis antigen ( TINAG ), and nudix hydrolase 6 ( NUDT6 ) [ 209 ].…”

Multi-Omics Data Analysis of Gene Expressions and Alterations, Cancer-Associated Fibroblast and Immune Infiltrations, Reveals the Onco-Immune Prognostic Relevance of STAT3/CDK2/4/6 in Human Malignancies

“…The use of bioinformatics for the identification of important cancer biomarkers is increasingly becoming a reliable and profitable method [ 26 , 27 ], owing to the availability of multi-omics clinical data including differentially expressed genes, mutation profile, therapeutic response, and survival profile of cancer patients in public databases providing a reliable guideline for the development of appropriate therapeutic intervention [ 12 ]. In addition, network analysis of multi-omics data has also helped our understanding of the epigenetic mechanism of cancer development and facilitated the discovery of epigenetic-based prognostic biomarkers and therapies [ 28 , 29 , 30 , 31 , 32 ]. In this study, we identified STAT3/CDK2/4/6 as an oncogenic prognosticator of cancer-associated fibroblasts and tumor immune infiltrations.…”