Related Experiment Video
Updated: May 11, 2026
Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
Published on: March 22, 2017
Detection of differentially methylated gene promoters in failing and nonfailing human left ventricle myocardium using
Christopher A Koczor1, Eva K Lee, Rebecca A Torres
1Department of Pathology, Emory University, Atlanta, Georgia, USA.
Insights
This study reveals key DNA methylation and gene expression changes in human dilated cardiomyopathy (DCM). Computational analysis identified novel gene promoters crucial for classifying DCM, offering new insights into heart failure development.
Area of Science:
- Genomics
- Epigenetics
- Cardiovascular Research
Background:
- Dilated cardiomyopathy (DCM) involves heart failure and altered gene expression.
- Epigenetic modifications, particularly DNA methylation, are suspected contributors to DCM pathogenesis.
- Extensive study of DNA methylation in human DCM is limited.
Purpose of the Study:
- To investigate DNA methylation and gene expression changes in human DCM.
- To identify specific gene promoters associated with DCM using computational analysis.
- To define a set of differentially methylated genes relevant to DCM classification.
Main Methods:
- Analysis of DNA methylation and gene expression in human DCM and control left ventricle samples.
- Utilized expression microarrays to identify differentially expressed genes.
- Employed two computational methods (subtractive analysis and a two-stage approach) for DNA methylation analysis of gene promoters.
Main Results:
- Identified 393 overexpressed and 349 underexpressed genes in DCM.
- Subtractive analysis revealed 158 gene promoters with methylation changes correlating to expression changes.
- Two-stage computational analysis identified 51 hypermethylated and six hypomethylated promoters with high accuracy.
- Four genes (AURKB, BTNL9, CLDN5, TK1) showed differential methylation and expression changes by both methods.
Conclusions:
- Rigorous computational analysis of microarray data can define clinically relevant DNA methylation and expression changes in DCM.
- The identified genes (AURKB, BTNL9, CLDN5, TK1) represent novel targets for DCM research.
- These findings contribute to a better understanding of the molecular mechanisms underlying DCM.
Abstract:
Human dilated cardiomyopathy (DCM) is characterized by congestive heart failure and altered myocardial gene expression. Epigenetic changes, including DNA methylation, are implicated in the development of DCM but have not been studied extensively. Clinical human DCM and nonfailing control left ventricle samples were individually analyzed for DNA methylation and expressional changes. Expression microarrays were used to identify 393 overexpressed and 349 underexpressed genes in DCM (GEO accession number: GSE43435). Gene promoter microarrays were utilized for DNA methylation analysis, and the resulting data were analyzed by two different computational methods. In the first method, we utilized subtractive analysis of DNA methylation peak data to identify 158 gene promoters exhibiting DNA methylation changes that correlated with expression changes. In the second method, a two-stage approach combined a particle swarm optimization feature selection algorithm and a discriminant analysis via mixed integer programming classifier to identify differentially methylated gene promoters. This analysis identified 51 hypermethylated promoters and six hypomethylated promoters in DCM with 100% cross-validation accuracy in the group assignment. Generation of a composite list of genes identified by subtractive analysis and two-stage computation analysis revealed four genes that exhibited differential DNA methylation by both methods in addition to altered gene expression. Computationally identified genes (AURKB, BTNL9, CLDN5, and TK1) define a central set of differentially methylated gene promoters that are important in classifying DCM. These genes have no previously reported role in DCM. This study documents that rigorous computational analysis applied to microarray analysis of healthy and diseased human heart samples helps to define clinically relevant DNA methylation and expressional changes in DCM.
