Calling differential DNA methylation at cell-type resolution: addressing misconceptions and best practices

• DOI: 10.1101/2021.02.14.431168
• Publication Date: 2021-02-16T03:25:28Z
• Authors: Elior Rahmani; Brandon Jew; Regev Schweiger; Brooke Rhead; Lindsey A. Criswell; Lisa F. Barcellos; Eleazar Eskin; Saharon Rosset; Sriram Sankararaman; Eran Halperin
• Keywords: 0301 basic medicine; 03 medical and health sciences

Abstract We benchmarked two approaches for the detection of cell-type-specific differential DNA methylation: Tensor Composition Analysis (TCA) and a regression model with interaction terms (CellDMC). Our experiments alongside rigorous mathematical explanations show that TCA is superior over CellDMC, thus resolving recent criticisms suggested by Jing et al. Following misconceptions colleagues modelling cell-type-specificity application TCA, we further discuss best practices performing association studies at cell-type resolution. The scripts reproducing all our results figures are publicly available github.com/cozygene/CellTypeSpecificMethylationAnalysis.