A Bayesian hierarchical model for analyzing methylated RNA immunoprecipitation sequencing data  

作　　者：Minzhe Zhangl Qiwei Lil Yang Xie 

机构地区：[1]Quantitative Biomedical Research Center,Department of Clinical Sciences,U.T.Southwestern Medical Center,Dallas,TX 75390,USA [2]Department of Bioinformatics,U.T.Southwestern Medical Center,Dallas,TX 75390,USA [3]Simmons Comprehensive Cancer Center,U.T.Southwestern Medical Center,Dallas,TX 75390,USA

出　　处：《Frontiers of Electrical and Electronic Engineering in China》2018年第3期275-286,共12页中国电气与电子工程前沿（英文版）

摘　　要：Background： The recently emerged technology of methylated RNA immunoprecipitation sequencing （MeRIP-seq） sheds light on the study of RNA epigenetics. This new bioinformatics question calls for effective and robust peaking calling algorithms to detect mRNA methylation sites from MeRIP-seq data. Methods： We propose a Bayesian hierarchical model to detect methylation sites from MeRIP-seq data. Our modeling approach includes several important characteristics. First, it models the zero-inflated and over-dispersed counts by deploying a zero-inflated negative binomial model. Second, it incorporates a hidden Markov model （HMM） to account for the spatial dependency of neighboring read enrichment. Third, our Bayesian inference allows the proposed model to borrow strength in parameter estimation, which greatly improves the model stability when dealing with MeRIP-seq data with a small number of replicates. We use Markov chain Monte Carlo （MCMC） algorithms to simultaneously infer the model parameters in a de novo fashion. The R Shiny demo is available at https：//qiwei. shinyapps.io/BaySeqPeak and the R/C ＋＋ code is available at https：//github.com/liqiwei2000/BaySeqPeak. Results： In simulation studies, the proposed method outperformed the competing methods exomePeak and MeTPeak, especially when an excess of zeros were present in the data. In real MeRIP-seq data analysis, the proposed method identified methylation sites that were more consistent with biological knowledge, and had better spatial resolution compared to the other methods. Conclusions： In this study, we develop a Bayesian hierarchical model to identify methylation peaks in MeRIP-seq data. The proposed method has a competitive edge over existing methods in terms of accuracy, robustness and spatial resolution.Background： The recently emerged technology of methylated RNA immunoprecipitation sequencing （MeRIP-seq） sheds light on the study of RNA epigenetics. This new bioinformatics question calls for effective and robust peaking calling algorithms to detect mRNA methylation sites from MeRIP-seq data. Methods： We propose a Bayesian hierarchical model to detect methylation sites from MeRIP-seq data. Our modeling approach includes several important characteristics. First, it models the zero-inflated and over-dispersed counts by deploying a zero-inflated negative binomial model. Second, it incorporates a hidden Markov model （HMM） to account for the spatial dependency of neighboring read enrichment. Third, our Bayesian inference allows the proposed model to borrow strength in parameter estimation, which greatly improves the model stability when dealing with MeRIP-seq data with a small number of replicates. We use Markov chain Monte Carlo （MCMC） algorithms to simultaneously infer the model parameters in a de novo fashion. The R Shiny demo is available at https：//qiwei. shinyapps.io/BaySeqPeak and the R/C ＋＋ code is available at https：//github.com/liqiwei2000/BaySeqPeak. Results： In simulation studies, the proposed method outperformed the competing methods exomePeak and MeTPeak, especially when an excess of zeros were present in the data. In real MeRIP-seq data analysis, the proposed method identified methylation sites that were more consistent with biological knowledge, and had better spatial resolution compared to the other methods. Conclusions： In this study, we develop a Bayesian hierarchical model to identify methylation peaks in MeRIP-seq data. The proposed method has a competitive edge over existing methods in terms of accuracy, robustness and spatial resolution.

关 键 词：MeRIP-seq data RNA epigenomics Bayesian inference hidden Markov model zero-inflated negativebinomial 

分 类 号：TP311.13[自动化与计算机技术—计算机软件与理论] Q78[自动化与计算机技术—计算机科学与技术]