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Fig. 3 | Genome Biology

Fig. 3

From: Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1

Fig. 3

Comparison between the DNA methylation changes during physiological aging and in Sotos. a Left: barplot showing the total number of differentially methylated positions (DMPs) found during physiological aging and in Sotos syndrome. CpG sites that increase their methylation levels with age in our healthy population or those that are elevated in Sotos patients (when compared with a control) are displayed in red. Conversely, those CpG sites that decrease their methylation levels are displayed in blue. Right: a table that represents the intersection between the aging (aDMPs) and the Sotos DMPs. The subset resulting from the intersection between the hypomethylated DMPs in aging and Sotos is called the “Hypo-Hypo DMPs” subset (N = 1728). b Enrichment for the categorical (epi) genomic features considered when comparing the different genome-wide subsets of differentially methylated positions (DMPs) in aging and Sotos against a control (see the “Methods” section). The y-axis represents the odds ratio (OR), the error bars show the 95% confidence interval for the OR estimate and the color of the points codes for -log10(p value) obtained after testing for enrichment using Fisher’s exact test. An OR > 1 shows that the given feature is enriched in the subset of DMPs considered, whilst an OR < 1 shows that it is found less than expected. In gray: features that did not reach significance using a significance level of α = 0.01 after Bonferroni correction. c Boxplots showing the distributions of the “normalised RNA expression” (NRE) when comparing the different genome-wide subsets of differentially methylated positions (DMPs) in aging and Sotos against a control (see the “Methods” section). NRE represents normalized mean transcript abundance in a window of ± 200 bp from the CpG site coordinate (DMP) being considered (see the “Methods” section). The p values (two-sided Wilcoxon’s test, before multiple testing correction) are shown above the boxplots. The number of DMPs belonging to each subset (in green) and the median value of the feature score (in dark red) are shown below the boxplots. d Same as c, but showing the “normalised fold change” (NFC) for the H3K36me3 histone modification (representing normalized mean ChIP-seq fold change for H3K36me3 in a window of ± 200 bp from the DMP being considered, see the “Methods” section)

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