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Open Access Highly Accessed Methodology article

The Triform algorithm: improved sensitivity and specificity in ChIP-Seq peak finding

Karl Kornacker1, Morten Beck Rye2, Tony Håndstad2 and Finn Drabløs2*

Author affiliations

1 Division of Sensory Biophysics, Ohio State University, Columbus, OH, USA

2 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), P.O. Box 8905, NO-7491, Trondheim, Norway

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Citation and License

BMC Bioinformatics 2012, 13:176  doi:10.1186/1471-2105-13-176

Published: 24 July 2012

Abstract

Background

Chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-Seq) is the most frequently used method to identify the binding sites of transcription factors. Active binding sites can be seen as peaks in enrichment profiles when the sequencing reads are mapped to a reference genome. However, the profiles are normally noisy, making it challenging to identify all significantly enriched regions in a reliable way and with an acceptable false discovery rate.

Results

We present the Triform algorithm, an improved approach to automatic peak finding in ChIP-Seq enrichment profiles for transcription factors. The method uses model-free statistics to identify peak-like distributions of sequencing reads, taking advantage of improved peak definition in combination with known characteristics of ChIP-Seq data.

Conclusions

Triform outperforms several existing methods in the identification of representative peak profiles in curated benchmark data sets. We also show that Triform in many cases is able to identify peaks that are more consistent with biological function, compared with other methods. Finally, we show that Triform can be used to generate novel information on transcription factor binding in repeat regions, which represents a particular challenge in many ChIP-Seq experiments. The Triform algorithm has been implemented in R, and is available via http://tare.medisin.ntnu.no/triform webcite.

Keywords:
ChIP-Seq; Peak finding; Benchmark; Repeats