Sierra platinum: a fast and robust peak-caller for replicated ChIP-seq experiments with visual quality-control and -steering

Abstract

BackgroundHistone modifications play an important role in gene regulation. Their genomic locations are of great interest. Usually, the location is measured by ChIP-seq and analyzed with a peak-caller. Replicated ChIP-seq experiments become more and more available. However, their analysis is based on single-experiment peak-calling or on tools like PePr which allows peak-calling of replicates but whose underlying model might not be suitable for the conditions under which the experiments are performed.ResultsWe propose a new peak-caller called ‘Sierra Platinum’ that allows peak-calling of replicated ChIP-seq experiments. Moreover, it provides a variety of quality measures together with integrated visualizations supporting the assessment of the replicates and the resulting peaks, as well as steering the peak-calling process.ConclusionWe show that Sierra Platinum outperforms currently available methods using a newly generated benchmark data set and using real data from the NIH Roadmap Epigenomics Project. It is robust against noisy replicates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1248-6) contains supplementary material, which is available to authorized users.

Analyzing Histone Modifications Using Tiled Binned Clustering and 3D Scatter Plots

“…As ChIP-seq data contains small errors and some DNA sequences are falsely aligned to regions within the genome, only the significant peaks within the genome-wide distribution of the mapped DNA sequences are treated as a valid histone modification mark (the method being applied is called 'peak-calling'). We used the peak-caller Sierra Platinum [18] to extract those significant regions having support by multiple replicates. Based on these peak calls we calculated a whole genome segmentation.…”

The Sierra Platinum Service for generating peak-calls for replicated ChIP-seq experiments

“…Afterwards, quality control information can be visually inspected (see Fig. 1 ) and parameters may be adjusted as for any local installation of Sierra Platinum (see Müller et al [ 7 ] for details). At any time, the results file can be downloaded for further, local analysis.…”

“…Tools for multi-replicate peak-calling were developed only recently. Among them, Sierra Platinum [ 7 ] combines multiple ChIP-seq experiments in a single peak calling process and thus makes full use of the information supplied by replicates. It provides extensive visualization options to guide the user through the evaluation of the experiments.…”

“…The GUI of Sierra Platinum further facilitates immediately comparing the impact of different parameter settings. Compared to other currently available peak-calling tools, Sierra Platinum performs best with respect to recall and false discovery rate regardless of the data quality [ 7 ].…”

Masakari: visualization supported statistical analysis of genome segmentations

“…We propose the tool "Masakari" for a data-driven segmentation of the genome: the segments are calculated based on the peaks describing chromatin modifications of genomic regions obtained using a peak caller like Sierra Platinum [5,6]. Masakari implements the segmentation proposed by Steiner et al [7].…”