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Fig. 1 | Genome Biology

Fig. 1

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

Fig. 1

Screening for epigenetic age acceleration (EAA) is improved when correcting for batch effects. a Flow diagram that portrays an overview of the different analyses that are carried out in the raw DNA methylation data (IDAT files) from human blood for cases (developmental disorders samples) and controls (healthy samples). The control samples are filtered to match the age range of the cases (0–55 years). The cases are filtered based on the number of “adult” samples available (for each disorder, at least 5 samples, with 2 of them with an age ≥ 20 years). More details can be found in the “Methods” section. QC, quality control; DMPs, differentially methylated positions. b Scatterplot showing the values of the first two principal components (PCs) for the control samples after performing PCA on the control probes of the 450K arrays. Each point corresponds to a different control sample, and the colors represent the different batches. The different batches cluster together in the PCA space, showing that the control probes indeed capture technical variation. Please note that all the PCA calculations were done with more samples from cases and controls than those that were included in the final screening since it was performed before the filtering step (see the “Methods” section and Fig. 1a). c Plot showing how the median absolute error (MAE) of the prediction in the control samples, that should tend to zero, is reduced when the PCs capturing the technical variation are included as part of the modeling strategy (see the “Methods” section). The dashed line represents the optimal number of PCs (17) that was finally used. The optimal mean MAE is calculated as the average MAE between the green and purple lines. CCC, cell composition correction. d Distribution of the EAA with cell composition correction (CCC) for the different control batches, after applying batch effect correction

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