PLEMT: A Novel Pseudolikelihood-Based EM Test for Homogeneity in Generalized Exponential Tilt Mixture Models
提出一种半参数混合模型和基于伪似然的EM检验，用于识别癌症组中差异甲基化位点，该检验能控制第一类错误且比现有方法更有效，尤其当两组方差不同时优势明显。
Motivated by analyses of DNA methylation data, we propose a semiparametric mixture model, namely the generalized exponential tilt mixture model, to account for heterogeneity between differentially methylated and non-differentially methylated subjects in the cancer group, and capture the differences in higher order moments (e.g. mean and variance) between subjects in cancer and normal groups. A pairwise pseudolikelihood is constructed to eliminate the unknown nuisance function. To circumvent boundary and non-identifiability problems as in parametric mixture models, we modify the pseudolikelihood by adding a penalty function. In addition, the test with simple asymptotic distribution has computational advantages compared with permutation-based test for high-dimensional genetic or epigenetic data. We propose a pseudolikelihood based expectation-maximization test, and show the proposed test follows a simple chi-squared limiting distribution. Simulation studies show that the proposed test controls Type I errors well and has better power compared to several current tests. In particular, the proposed test outperforms the commonly used tests under all simulation settings considered, especially when there are variance differences between two groups. The proposed test is applied to a real data set to identify differentially methylated sites between ovarian cancer subjects and normal subjects.