Journal: Basic Research in Cardiology
Article Title: Indirect epigenetic testing identifies a diagnostic signature of cardiomyocyte DNA methylation in heart failure
doi: 10.1007/s00395-022-00954-3
Figure Lengend Snippet: DNA methylation changes detected in the indirect cardiomyocyte test. A MDS plot of top-10,000 CpG probes within the Illumina ® HumanMethylation450k array performed on inducible pluripotent stem cell (iPSC)-derived cardiomyocytes exposed to plasma from patients with end-stage heart failure (DCM; n = 13) relative to plasma from healthy (CON; n = 10) patients. B Volcano plot illustrating the robustness of CpG methylation differences, plotting (- log 10 [ P value]) as a function of percent difference in methylation (%) in DCM vs. CON, probes P < 0.05 and |methylation %|> 5 are highlighted in yellow. Labelled are the 10 most-robustly hyper-methylated and hypo-methylated CpG probes by % methylation. C Distribution of differential methylation via three-dimensional contour plot of differentially methylated CpG probes (DMPs)* categorized according to their presence within genomic (Promoter, 5’ UTR, Body, Exon–Intron boundary, or 3’ UTR) and CpG (Shelf, Shore, and Island) regions. Bar graph depicting the number of DMPs within each genomic region. D proportional distribution of CpG Island-associated DMPs. E Heatmap and hierarchical clustering of DMPs according to each genomic region. *DMPs defined via P < 0.05
Article Snippet: Human inducible pluripotent stem cells (iPSC-CMs) were treated with plasma from either DCM ( n = 13) or healthy ( n = 10) subjects for 48 h. Samples were then analyzed for cell size using InCell Analyzer and submitted for methylation analysis with the Illumina TM Beadchip HumanMethylation450k (m450k) Array platform.
Techniques: DNA Methylation Assay, Derivative Assay, Clinical Proteomics, CpG Methylation Assay, Methylation
![Cardiac DNA methylation in cardiac biopsies. A Multidimensional scaling (MDS) of top-10,000 CpG probes within the Illumina ® HumanMethylation450k array performed on cardiac left ventricle samples from patients with end-stage heart failure (DCM) or non-failing donor control hearts (CON). The two principal components that account from the largest variance in DNA methylation were used to generate a scatterplot, flanked by density plots of each principal component. B Volcano plot illustrating the robustness of CpG methylation differences, plotting (– log 10 [ P value]) as a function of percent difference in methylation (%) in DCM vs. CON, probes exceeding P < 0.05 and |methylation %|> 5 highlighted in yellow. Labelled are the 10 most-robustly hyper-methylated and hypo-methylated CpG probes by % methylation. C Distribution of differential methylation via three-dimensional contour plot of differentially methylated CpG probes (DMPs)* categorized according to their presence within genomic (Promoter, 5’ UTR, Body, Exon–Intron boundary, or 3’ UTR) and CpG (Shelf, Shore, and Island) regions. Bar graph depicting the number of DMPs within each genomic region. D proportional distribution of CpG Island-associated DMPs. E Heatmap and hierarchical clustering of DMPs according to each genomic region. * P < 0.05](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_7651/pmc10027651/pmc10027651__395_2022_954_Fig3_HTML.jpg)
![DNA methylation changes detected in the indirect cardiomyocyte test. A MDS plot of top-10,000 CpG probes within the Illumina ® HumanMethylation450k array performed on inducible pluripotent stem cell (iPSC)-derived cardiomyocytes exposed to plasma from patients with end-stage heart failure (DCM; n = 13) relative to plasma from healthy (CON; n = 10) patients. B Volcano plot illustrating the robustness of CpG methylation differences, plotting (- log 10 [ P value]) as a function of percent difference in methylation (%) in DCM vs. CON, probes P < 0.05 and |methylation %|> 5 are highlighted in yellow. Labelled are the 10 most-robustly hyper-methylated and hypo-methylated CpG probes by % methylation. C Distribution of differential methylation via three-dimensional contour plot of differentially methylated CpG probes (DMPs)* categorized according to their presence within genomic (Promoter, 5’ UTR, Body, Exon–Intron boundary, or 3’ UTR) and CpG (Shelf, Shore, and Island) regions. Bar graph depicting the number of DMPs within each genomic region. D proportional distribution of CpG Island-associated DMPs. E Heatmap and hierarchical clustering of DMPs according to each genomic region. *DMPs defined via P < 0.05](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_7651/pmc10027651/pmc10027651__395_2022_954_Fig4_HTML.jpg)
