Fig. 1

Computational framework of MethylTransition. a Schematic overview of DNA methylation changes during mitosis. MethylTransition relies on the assumption that changes in the DNA methylation state at a CpG site across a single cell cycle occur in three steps: passive demethylation during DNA replication, active DNA methylation by DNA methylation-modifying enzymes, and DNA methylation state combination during the combination of non-sister chromatids. The open circle represents a CpG dinucleotides with an unmethylated C, and the solid circle represents a CpG dinucleotides with a methylated C. In the first step, DNA replication, the newly synthetized strand (gray) is unmethylated. In the second step, enzyme action, the DNA methylation state in a CpG dyad can be changed by different enzymes. In the third step, non-sister chromatid combination, the observed DNA methylation state of a CpG site in a single cell is the combination of the DNA methylation states from both homologous chromosomes for diploid organisms. b Transition probabilities among DNA methylation states during DNA replication and enzyme action. We used 1 as a symbol to represent a CpG dinucleotides with a methylated C and 0 to represent a CpG dinucleotides with an unmethylated C. The DNA methylation state for a CpG dyad can be unmethylated (0-0), hemi-methylated (0-1 or 1-0), or fully methylated (1-1). The upper panel shows the transition probabilities among states during DNA replication, where a represents the probability of parental DNA being present in one of two daughter strands and is 0.5 for the symmetric division. The lower panel shows the transition probabilities among states during enzyme action, where u is the probability of de novo methylation on an unmethylated CpG dyad, p is the probability of methylation maintenance on a hemi-methylated CpG dyad, and d is the probability of active demethylation on a methylated or hemi-methylated CpG dyad