Cell-Type Deconvolution of Bulk DNA Methylation Data with EpiSCORE

DNA methylation data generated from bulk tissue represents a mixture of many different cell types. Variation in the cell-type composition of tissues is thus a major confounder when inferring differential DNA methylation. Due to the high cost of single-cell methylome sequencing, computational methods that can dissect the cell-type heterogeneity of bulk DNA methylomes offer an efficient and cost-effective solution, especially in the context of large-scale EWAS. In this chapter, we present a step-by-step tutorial of Epigenetic cell-type deconvolution using Single-Cell Omic References (EpiSCORE), a reference-based method that leverages the high-resolution nature of single-cell RNA-Seq datasets to facilitate microdissection of bulk-tissue DNA methylomes.