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By averaging each CpG site’s methylation over all cells and subsequent smoothing, the ‘average methylation’ (thick black curve) is obtained. To quantify the methylation of cell 1 from a relative to this average over all cells, we propose to use the cell’s residuals to the smoothed curve (the lengths of the vertical red lines) and take their average, counting residuals of methylated CpGs as positive and residuals of unmethylated CpGs as negative.
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