title: Epigenetic change detection and pattern recognition via Bayesian hierarchical hidden Markov models.
abstract: Epigenetics is the study of changes to the genome that can switch genes on or off and determine which proteins are transcribed without altering the DNA sequence. Recently, epigenetic changes have been linked to the development and progression of disease such as psychiatric disorders. High-throughput epigenetic experiments have enabled researchers to measure genome-wide epigenetic profiles and yield data consisting of intensity ratios of immunoprecipitation versus reference samples. The intensity ratios can provide a view of genomic regions where protein binding occur under one experimental condition and further allow us to detect epigenetic alterations through comparison between two different conditions. However, such experiments can be expensive, with only a few replicates available. Moreover, epigenetic data are often spatially correlated with high noise levels. In this paper, we develop a Bayesian hierarchical model, combined with hidden Markov processes with four states for modeling spatial dependence, to detect genomic sites with epigenetic changes from two-sample experiments with paired internal control. One attractive feature of the proposed method is that the four states of the hidden Markov process have well-defined biological meanings and allow us to directly call the change patterns based on the corresponding posterior probabilities. In contrast, none of existing methods can offer this advantage. In addition, the proposed method offers great power in statistical inference by spatial smoothing (via hidden Markov modeling) and information pooling (via hierarchical modeling). Both simulation studies and real data analysis in a cocaine addiction study illustrate the reliability and success of this method.
authors.affiliation: Department of Statistical Science, Southern Methodist University, Dallas, TX 75275, USA.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Zang
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D050882:CREB-Binding Protein / Q000235:genetics; D019970:Cocaine-Related Disorders / Q000235:genetics; D003198:Computer Simulation; D044127:Epigenesis, Genetic; D016678:Genome; D006801:Humans; D008390:Markov Chains; D051379:Mice; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse