DNA methylation is on the base level a binary mark. However, when calculating average methylation rates across cells in bulk samples, certain regions of the genome exhibit intermediate methylation values, indicating heterogeneous methylation patterns.
Conceptually, DNA methylation can be heterogeneous across cells but also show disordered/aberrant patterns along the sequence of a single cell, e.g. due stochastic loss of DNA methylation.
Here, an approach considering two different entropy measures is proposed to differentiate between sources of DNA methylation heterogeneity in regions of intermediate DNA methylation, by utilizing single-cell bisulfite sequencing data.