Fig. 2: The inference landscape for methylation and demethylation rates.
a Inference landscape for kde (left) and kme (right), respectively, given all 6400 possible combinations tested (see “Methods”). Blue regions represent high-confidence regimes were rates can be accurately inferred, whereas CpGs lying in the green to yellow regimes are increasingly difficult and ultimately impossible to determine with high confidence. Confidence levels were determined by an error model explicitly detailed in “Methods”. b Example pairs of CpGs and their placement in the inference landscape. Theoretical decay curves for the point pairs (connected by dashed lines) are shown to the right. Each pair number trajectory from the far left panel is shown individually in the right four panels. Note, rates for some CpGs can be accurately distinguished (1), while others have reduced confidence (3) or are governed by rates that are not possible to determine (2 and 4). c Points representing rate combinations for all CpGs (405) measured with amplicon sequencing. Points are overlaid on the inference landscape taking both kde and kme into account, inference colors are as a. Blue points have low noise in rate inference, while red points represent CpGs where noise is high. Black points represent CpGs where rates cannot be determined. Because the logarithm of the rates is displayed on both axes, lines with a slope of one (cases 1–3) correspond to rate combinations that result in the same steady-state methylation level but with different turnover.
