ChIP-Sequencing (ChIP-Seq) provides a vast amount of information regarding the localization of proteins across the genome. The aggregation of ChIP-Seq enrichment signal in a metagene plot is an approach commonly used to summarize data complexity and to obtain a high level visual representation of the general occupancy pattern of a protein. Here we present the R package metagene, the graphical interface Imetagene and the companion package similaRpeak. Together, they provide a framework to integrate, summarize and compare the ChIP-Seq enrichment signal from complex experimental designs. Those packages identify and quantify similarities or dissimilarities in patterns between large numbers of ChIP-Seq profiles. We used metagene to investigate the differential occupancy of regulatory factors at noncoding regulatory regions (promoters and enhancers) in relation to transcriptional activity in GM12878 B-lymphocytes. The relationships between occupancy patterns and transcriptional activity suggest two different mechanisms of action for transcriptional control: i) a “gradient effect” where the regulatory factor occupancy levels follow transcription and ii) a “threshold effect” where the regulatory factor occupancy levels max out prior to reaching maximal transcription. metagene, Imetagene and similaRpeak are implemented in R under the Artistic license 2.0 and are available on Bioconductor.
Genome-wide mapping of nucleosomes has revealed a great deal about the relationships between chromatin structure and control of gene expression. Recent next generation CHIP-chip and CHIP-Seq technologies have accelerated our understanding of basic principles of chromatin organization. These technologies have taught us that nucleosomes play a crucial role in gene regulation by allowing physical access to transcription factors. Recent methods and experimental advancements allow the determination of nucleosome positions for a given genome area. However, most of these methods estimate the number of nucleosomes either by an EM algorithm using a BIC criterion or an effective heuristic strategy. Here, we introduce a Bayesian method for identifying nucleosome positions. The proposed model is based on a Multinomial-Dirichlet classification and a hierarchical mixture distributions. The number and the positions of nucleosomes are estimated using a reversible jump Markov chain Monte Carlo simulation technique. We compare the performance of our method on simulated data and MNase-Seq data from Saccharomyces cerevisiae against PING and NOrMAL methods.
Consider the semiparametric transformation model Λ θo (Y ) = m(X) + ε, where θo is an unknown finite dimensional parameter, the functions Λ θo and m are smooth, ε is independent of X, and E(ε) = 0.We propose a kernel-type estimator of the density of the error ε, and prove its asymptotic normality. The estimated errors, which lie at the basis of this estimator, are obtained from a profile likelihood estimator of θo and a nonparametric kernel estimator of m. The practical performance of the proposed density estimator is evaluated in a simulation study.
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