A Bayesian Framework for Estimating Cell Type Composition from DNA Methylation Without the Need for Methylation Reference

We introduce a Bayesian semi-supervised method for estimating cell counts from DNA methylation by leveraging an easily obtainable prior knowledge on the cell type composition distribution of the studied tissue. We show mathematically and empirically that alternative methods which attempt to infer explicit cell counts without methylation reference can only capture linear combinations of cell counts rather than provide one component per cell type. Our approach, which allows the construction of a set of components such that each component corresponds to a single cell type, therefore provides a new opportunity to investigate cell compositions in genomic studies of tissues for which it was not possible before.