Zerone: a ChIP-seq discretizer for multiple replicates with built-in quality control

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Motivation: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is the standard method to investigate chromatin protein composition. As the number of community-available ChIP-seq profiles increases, it becomes more common to use data from different sources, which makes joint analysis challenging. Issues such as lack of reproducibility, heterogeneous quality and conflicts between replicates become evident when comparing datasets, especially when they are produced by different laboratories.

Results: Here, we present Zerone, a ChIP-seq discretizer with built-in quality control. Zerone is powered by a Hidden Markov Model with zero-inflated negative multinomial emissions, which allows it to merge several replicates into a single discretized profile. To identify low quality or irreproducible data, we trained a Support Vector Machine and integrated it as part of the discretization process. The result is a classifier reaching 95% accuracy in detecting low quality profiles. We also introduce a graphical representation to compare discretization quality and we show that Zerone achieves outstanding accuracy. Finally, on current hardware, Zerone discretizes a ChIP-seq experiment on mammalian genomes in about 5 min using less than 700 MB of memory.

Availability and Implementation: Zerone is available as a command line tool and as an R package. The C source code and R scripts can be downloaded from The information to reproduce the benchmark and the figures is stored in a public Docker image that can be downloaded from


Supplementary information: Supplementary data are available at Bioinformatics online.

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