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

Lydia Müller, Daniel Gerighausen, Mariam Farman, Dirk Zeckzer

Histone 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. We 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. We 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.