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Fig. 5 | Epigenetics & Chromatin

Fig. 5

From: Systematic prediction of DNA shape changes due to CpG methylation explains epigenetic effects on protein–DNA binding

Fig. 5

Modeling of methylation-induced shifts in cleavage rates using methylation-induced shifts in shape feature profile. a Points on plot represent inferred binding free energy (ΔΔG/RT) values of DNase I to unmethylated hexamers and corresponding methylated hexamers with absolute phosphate cleavage count ≥ 25. Methylation-induced effects are shown for sequences with C+1G+2 offset. Shift (downward) from diagonal indicates log-fold increase in cleavage activity of DNase I for methylated hexamers. b Shape-to-affinity modeling and use of methyl-DNAshape features. Shape-to-affinity model (L1- and L2-regularized linear regression model) built using unmethylated data. DNA shape features for unmethylated hexamers and their corresponding free energies (ΔΔG/RT) were used as predictors and response variables, respectively. The model used the methylation effects on shape features (Δshape) calculated by methyl-DNAshape to predict ΔΔΔG (methylation effects on free energy, indicated by ΔΔΔĜ). Linearity of the model allowed direct use of Δshape as input variable. Roll values are shown for illustration purposes. c Predictive powers of different shape-based models. Observed ΔΔΔG/RT with median around − 2 is shown in gray colored box. Roll-based model accurately predicts the cleavage bias for C+1G+2 offset

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