Guidelines for cell-type heterogeneity quantification based on a comparative analysis of reference-free DNA methylation deconvolution software

摘要

Performance of the 3 deconvolution methods for different parameter settings. Heatmap of method performance (`A MAE`: Mean Absolute Error on estimated A, the matrix of cell proportions). RFE stands for RefFreeEWAS, MDC for MeDeCom and EDec for EDec stage 1. All algorithms were run on 10 D matrices corresponding to 10 different realizations of the random - controlled process on one D matrix computed from one simulated A matrix, each time, with the following parameters n (number of samples), α (inter-sample variation in mixture proportion), (magnitude of random noise applied on D) and G (the cell profiles used for simulations). Mean MAE corresponds to the average error of the three methods (computed for each parameter set). A random A matrix was used for testing the effect of G1 and G2, another random A matrix was used for testing the effect of magnitude. Testing the effect of n and α required independent simulation of A each time. As a consequence, the four simulations corresponding to the set of parameters  = 100, α  = 1, = 0.2, G = 1 have different results, because these simulations are based on different randomly simulated A matrices (see Fig.  for a systematic analysis of performance variation according to the random simulations of A)