Chapter 20 - Epigenetic intratumoral heterogeneity

Abstract

DNA methylation is one of the epigenetic biomarkers that researchers have used substantially in cancer research, such as in epigenome-wide association studies (EWAS). However, due to the cell-type-specific DNA methylation pattern, cell-type heterogeneity presents a significant challenge for the inference and interpretation of EWAS. Here, we illustrate how the bulk DNA methylation measurements are affected by cell-type composition and summarize existing reference-based and reference-free statistical methods to identify differentially methylated CpGs when adjusting for cell-type heterogeneity, as well as methods to identify differentially methylated cell type(s). By discussing the underlying assumptions of these statistical methods, we hope to help readers choose and use these methods in cancer EWAS for more accurate inference.