SigSeeker: a peak-calling ensemble approach for constructing epigenetic signatures

Abstract

Epigenetic data are invaluable when determining the regulatory programs governing a cell. Based on use of next-generation sequencing data for characterizing epigenetic marks and transcription factor binding, numerous peak-calling approaches have been developed to determine sites of genomic significance in these data. Such analyses can produce a large number of false positive predictions, suggesting that sites supported by multiple algorithms provide a stronger foundation for inferring and characterizing regulatory programs associated with the epigenetic data. Few methodologies integrate epigenetic based predictions of multiple approaches when combining profiles generated by different tools. The SigSeeker peak-calling ensemble uses multiple tools to identify peaks, and with user-defined thresholds for peak overlap and signal strength it retains only those peaks that are concordant across multiple tools. Peaks predicted to be co-localized by only a very small number of tools, discovered to be only marginally overlapping, or found to represent significant outliers to the approximation model are removed from the results, providing concise and high quality epigenetic datasets. SigSeeker has been validated using established benchmarks for transcription factor binding and histone modification ChIP-Seq data. These comparisons indicate that the quality of our ensemble technique exceeds that of single tool approaches, enhances existing peak-calling ensembles, and results in epigenetic profiles of higher confidence. http://sigseeker.org. lichtenbergj@mail.nih.gov. Supplementary data are available at Bioinformatics online.