Dataset Information

The Bayesian Expectation-Maximization-Maximization for the 3PLM.

ABSTRACT: The current study proposes an alternative feasible Bayesian algorithm for the three-parameter logistic model (3PLM) from a mixture-modeling perspective, namely, the Bayesian Expectation-Maximization-Maximization (Bayesian EMM, or BEMM). As a new maximum likelihood estimation (MLE) alternative to the marginal MLE EM (MMLE/EM) for the 3PLM, the EMM can explore the likelihood function much better, but it might still suffer from the unidentifiability problem indicated by occasional extremely large item parameter estimates. Traditionally, this problem was remedied by the Bayesian approach which led to the Bayes modal estimation (BME) in IRT estimation. The current study attempts to mimic the Bayes modal estimation method and develop the BEMM which, as a combination of the EMM and the Bayesian approach, can bring in the benefits of the two methods. The study also devised a supplemented EM method to estimate the standard errors (SEs). A simulation study and two real data examples indicate that the BEMM can be more robust against the change in the priors than the Bayes modal estimation. The mixture modeling idea and this algorithm can be naturally extended to other IRT with guessing parameters and the four-parameter logistic models (4PLM).

SUBMITTER: Guo S

PROVIDER: S-EPMC6555200 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Bayesian Expectation-Maximization-Maximization for the 3PLM.

Guo Shaoyang S Zheng Chanjin C

Frontiers in psychology 20190531

The current study proposes an alternative feasible Bayesian algorithm for the three-parameter logistic model (3PLM) from a mixture-modeling perspective, namely, the Bayesian Expectation-Maximization-Maximization (Bayesian EMM, or BEMM). As a new maximum likelihood estimation (MLE) alternative to the marginal MLE EM (MMLE/EM) for the 3PLM, the EMM can explore the likelihood function much better, but it might still suffer from the unidentifiability problem indicated by occasional extremely large i ...[more]

PMID: 31214067

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Project description:Genome-wide nucleosome profiles are predominantly characterized using MNase-seq, which involves extensive MNase digestion and size selection to enrich for mono-nucleosome-sized fragments. Most available MNase-seq analysis packages assume that nucleosomes uniformly protect 147bp DNA fragments. However, some nucleosomes with atypical histone or chemical compositions protect shorter lengths of DNA. The rigid assumptions imposed by current nucleosome analysis packages ignore variation in nucleosome lengths, potentially blinding investigators to regulatory roles played by atypical nucleosomes. To enable the characterization of different nucleosome types from MNase-seq data, we introduce the Size-based Expectation Maximization (SEM) nucleosome calling package. SEM employs a hierarchical Gaussian mixture model to estimate the positions and subtype identity of nucleosomes from MNase-seq fragments. Nucleosome subtypes are automatically identified based on the distribution of protected DNA fragment lengths at nucleosome positions. Benchmark analysis indicates that SEM is on par with existing packages in terms of standard nucleosome-calling accuracy metrics, while uniquely providing the ability to characterize nucleosome subtype identities. Using SEM on a low-dose MNase H2B MNase-ChIP-seq dataset from mouse embryonic stem cells, we identified three nucleosome types: short-fragment nucleosomes, canonical nucleosomes, and di-nucleosomes. The short-fragment nucleosomes can be divided further into two subtypes based on their chromatin accessibility. Interestingly, the subset of short-fragment nucleosomes in accessible regions exhibit high MNase sensitivity and display distribution patterns around transcription start sites (TSSs) and CTCF peaks, similar to the previously reported "fragile nucleosomes". These SEM-defined accessible short-fragment nucleosomes are found not just in promoters, but also in enhancers and other regulatory regions. Additional investigations reveal their co-localization with the chromatin remodelers Chd6, Chd8, and Ep400. In summary, SEM provides an effective platform for distinguishing various nucleosome subtypes, paving the way for future exploration of non-standard nucleosomes.

Dataset Information

The Bayesian Expectation-Maximization-Maximization for the 3PLM.

Publications

The Bayesian Expectation-Maximization-Maximization for the 3PLM.

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