Identifying dispersed epigenomic domains from ChIP-Seq data

Abstract

Motivation: Post-translational modifications to histones have several well known associations with regulation of gene expression. While some modifications appear concentrated narrowly, covering promoters or enhancers, others are dispersed as epigenomic domains. These domains mark contiguous regions sharing an epigenomic property, such as actively transcribed or poised genes, or heterochromatically silenced regions. While high-throughput methods like ChIP-Seq have led to a flood of high-quality data about these epigenomic domains, there remain important analysis problems that are not adequately solved by current analysis tools.Results: We present the RSEG method for identifying epigenomic domains from ChIP-Seq data for histone modifications. In contrast with other methods emphasizing the locations of ‘peaks’ in read density profiles, our method identifies the boundaries of domains. RSEG is also able to incorporate a control sample and find genomic regions with differential histone modifications between two samples.Availability: RSEG, including source code and documentation, is freely available at http://smithlab.cmb.usc.edu/histone/rseg/.Contact: anrewds@usc.eduSupplementary information: Supplementary data are available at Bioinformatics online.

Epigenetic dysregulation by nickel through repressive chromatin domain disruption

“…After saturation analysis of the ChIP-Seq reads to ensure sufficient coverage (SI Materials and Methods and Fig. S2), we called all domains in both control (Ctrl) and Ni-treated (Ni) cells using RSEG software (25). To validate H3K9me2 ChIP-Seq data and to optimize H3K9me2 domain calling, we selected several loci and performed ChIPquantitative PCR (qPCR) analysis on untreated and Ni-treated cells ( Fig.…”

An introduction to computational tools for differential binding analysis with ChIP‐seq data

“…There are computational tools that are specifically devised to handle such situations. For example, SICER is developed to identify large spatial clusters of ChIP-seq reads [26], while RSEG utilizes a hidden Markov model (HMM) to detect broad epigenomic domains with consecutively elevated ChIP-seq signals [32]. Notably, both MACS and SICER accept a treatment ChIP-seq sample and an optional input sample as the negative control for peak calling.…”

“…One of them scans the whole genome with a sliding window and consecutively performs the same statistical test on the ChIP-seq signals at each window [49,50], where the window size is usually selected to match the typical size of a ChIP-seq signal enriched region. The other class takes advantage of more sophisticated segmentation techniques such as HMM [15,32,47,48], where the genome is fragmented into sequences of bins and a putative hidden state is then inferred for each bin to indicate whether it is associated with differential ChIP-seq signal ( Figure 1, lower right). One of the reasons accounting for the superiority of using an HMM is that, for a target bin, it incorporates ChIP-seq signals lying in the vicinity to improve the inference made for the bin.…”

A Novel Bayesian Change-point Algorithm for Genome-wide Analysis of Diverse ChIPseq Data Types

“…Hidden Markov Models (HMMs) [6][7][8] . We sought a solution that minimized the necessity for difficult-to-define, ad hoc parameters that often compromise resolution and lessen the intuitive usability of the tool.…”

“…For example, transcription factors often bind in a site-and sequence-specific manner and tend to produce punctate peaks, while histone modifications are more pervasive and are characterized by broad, diffuse islands of enrichment 2 . Reliably identifying these regions was the focus of our work.Algorithms for analyzing ChIPseq data have employed various methodologies, from heuristics 3-5 to more rigorous statistical models, e.g.Hidden Markov Models (HMMs) [6][7][8] . We sought a solution that minimized the necessity for difficult-to-define, ad hoc parameters that often compromise resolution and lessen the intuitive usability of the tool.…”