title: A Poisson mixture model to identify changes in RNA polymerase II binding quantity using high-throughput sequencing technology.
abstract: We present a mixture model-based analysis for identifying differences in the distribution of RNA polymerase II (Pol II) in transcribed regions, measured using ChIP-seq (chromatin immunoprecipitation following massively parallel sequencing technology). The statistical model assumes that the number of Pol II-targeted sequences contained within each genomic region follows a Poisson distribution. A Poisson mixture model was then developed to distinguish Pol II binding changes in transcribed region using an empirical approach and an expectation-maximization (EM) algorithm developed for estimation and inference. In order to achieve a global maximum in the M-step, a particle swarm optimization (PSO) was implemented. We applied this model to Pol II binding data generated from hormone-dependent MCF7 breast cancer cells and antiestrogen-resistant MCF7 breast cancer cells before and after treatment with 17beta-estradiol (E2). We determined that in the hormone-dependent cells, approximately 9.9% (2527) genes showed significant changes in Pol II binding after E2 treatment. However, only approximately 0.7% (172) genes displayed significant Pol II binding changes in E2-treated antiestrogen-resistant cells. These results show that a Poisson mixture model can be used to analyze ChIP-seq data.
authors.affiliation: Division of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. wfeng@compbio.iupui.edu
authors.forename: Weixing
authors.initials: W
authors.lastname: Feng
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiejun
authors.initials: J
authors.lastname: Wu
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
authors.forename: Tim H M
authors.initials: TH
authors.lastname: Huang
authors.forename: Lang
authors.initials: L
authors.lastname: Li
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004958:Estradiol / Q000494:pharmacology; D015894:Genome, Human; D006801:Humans; D015233:Models, Statistical; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016012:Poisson Distribution; D011485:Protein Binding; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*
chemical_list: D004958:Estradiol; D012319:RNA Polymerase II