A systematic assessment of cell type deconvolution algorithms for DNA methylation data

Abstract

Abstract We performed systematic assessment of computational deconvolution methods that play an important role in the estimation of cell type proportions from bulk methylation data. The proposed framework methylDeConv (available as an R package) integrates several deconvolution methods for methylation profiles (Illumina HumanMethylation450 and MethylationEPIC arrays) and offers different cell-type-specific CpG selection to construct the extended reference library which incorporates the main immune cell subsets, epithelial cells and cell-free DNAs. We compared the performance of different deconvolution algorithms via simulations and benchmark datasets and further investigated the associations of the estimated cell type proportions to cancer therapy in breast cancer and subtypes in melanoma methylation case studies. Our results indicated that the deconvolution based on the extended reference library is critical to obtain accurate estimates of cell proportions in non-blood tissues.