A Hierarchical Bayesian Approach to Detect DifferentiallyMethylated Loci from Bisulfite Sequencing Data Open Access

Abstract

DNA methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. In studies of DNA methylation, one key task is to identify methylation differences under distinct biological contexts. Recently, as bisulfite sequencing technology (BS-seq) has made it possible to detect methylation in CG loci level, more and more datasets are becoming available to study DNA methylation. A common drawback of datasets in these studies; however, is that the number of sample replicates is usually limited. This can lead to unstable estimation of within group variance, and may subsequently yield unsatisfactory results in differentially methylated loci (DML) detection. Here we propose a new method to apply shrinkage to the variance estimation in an empirical Bayes model. We show that the variance shrinkage in these data can be done by shrinking a dispersion parameter. Simulation results demonstrate the favorable performance of the new methods.

Table of Contents

Introduction ............................................... Page 1

Methods ............................................... Page 5

Results ............................................... Page 12

Discussion ............................................... Page 23

Reference ............................................... Page 25

About this Master's Thesis

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School	Rollins School of Public Health
Department	Biostatistics and Bioinformatics
Subfield / Discipline	Biostatistics - MPH & MSPH
Degree	MSPH
Submission	Master's Thesis
Language	English
Research Field	Biology, Genetics Biology, Biostatistics Biology, Bioinformatics
Keyword	DNA methylation Dispersion Parameter Beta-Binomial Empirical Bayes Shrinkage Estimator Bisulfite Sequencing
Committee Chair / Thesis Advisor	Conneely, Karen N, Emory University Wu, Hao, Emory University
Committee Members	Hu, Yijuan, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

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