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Open Access Highly Accessed Methodology article

Predicting tissue specific transcription factor binding sites

Shan Zhong, Xin He and Ziv Bar-Joseph*

Author Affiliations

Lane Center for Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, 15213, USA

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BMC Genomics 2013, 14:796  doi:10.1186/1471-2164-14-796

Published: 15 November 2013

Abstract

Background

Studies of gene regulation often utilize genome-wide predictions of transcription factor (TF) binding sites. Most existing prediction methods are based on sequence information alone, ignoring biological contexts such as developmental stages and tissue types. Experimental methods to study in vivo binding, including ChIP-chip and ChIP-seq, can only study one transcription factor in a single cell type and under a specific condition in each experiment, and therefore cannot scale to determine the full set of regulatory interactions in mammalian transcriptional regulatory networks.

Results

We developed a new computational approach, PIPES, for predicting tissue-specific TF binding. PIPES integrates in vitro protein binding microarrays (PBMs), sequence conservation and tissue-specific epigenetic (DNase I hypersensitivity) information. We demonstrate that PIPES improves over existing methods on distinguishing between in vivo bound and unbound sequences using ChIP-seq data for 11 mouse TFs. In addition, our predictions are in good agreement with current knowledge of tissue-specific TF regulation.

Conclusions

We provide a systematic map of computationally predicted tissue-specific binding targets for 284 mouse TFs across 55 tissue/cell types. Such comprehensive resource is useful for researchers studying gene regulation.