Optimized functional annotation of ChIP-seq data

Abstract

Motivation: Different ChIP-seq peak callers often produce different output results from the same input. Since different peak callers are known to produce differentially enriched peaks with a large variance in peak length distribution and total peak count, accurately annotating peak lists with their nearest genes can be an arduous process. Functional genomic annotation of histone modification ChIP-seq data can be a particularly challenging task, as chromatin marks that have inherently broad peaks with a diffuse range of signal enrichment (e.g., H3K9me1, H3K27me3) differ significantly from narrow peaks that exhibit a compact and localized enrichment pattern (e.g., H3K4me3, H3K9ac). In addition, varying degrees of tissue-dependent broadness of an epigenetic mark can make it difficult to accurately and reliably link sequencing data to biological function. Thus, it would be useful to develop a software program that can precisely tailor the computational analysis of a ChIP-seq dataset to the specific peak coordinates of the data. Results: geneXtendeR is an R/Bioconductor package that optimizes the functional annotation of ChIPseq peaks using fast iterative peak-coordinate/GTF alignment algorithms focused on cis-regulatory regions and proximal-promoter regions of nearest genes. The goal of geneXtendeR is to robustly link differentially enriched peaks with their respective genes, thereby aiding experimental follow-up and validation in designing primers for a set of prospective gene candidates during qPCR. We have tested geneXtendeR on 547 human transcription factor ChIP-seq ENCODE datasets and 214 human histone modification ChIPseq ENCODE datasets, providing the analysis results as case studies. Availability: The geneXtendeR R/Bioconductor package (including detailed introductory vignettes) is available under the GPL-3 Open Source license and is freely available to download from Bioconductor at: https://bioconductor.org/packages/devel/geneXtendeR/.

SUPERmerge: ChIP-seq coverage island analysis algorithm for broad histone marks

“…It is known that epigenetic histone modifications that have inherently broad peaks with a diffuse range of signal enrichment (e.g., H3K9me1, H3K27me3) differ significantly from narrow peaks that exhibit a compact and localized enrichment pattern (e.g., H3K4me3, H3K9ac) [15]. Likewise, transcription factors that exhibit punctate protein-DNA enrichment patterns resulting in narrow and well-defined peaks differ significantly from the broad peaks frequently detected in diffuse chromatin mark data.…”