Discriminative motif analysis of high-throughput dataset

Zizhen Yao*, Kyle L. Macquarrie, Abraham P. Fong, Stephen J. Tapscott, Walter L. Ruzzo, Robert C. Gentleman

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Motivation: High-throughput ChIP-seq studies typically identify thousands of peaks for a single transcription factor (TF). It is common for traditional motif discovery tools to predict motifs that are statistically significant against a naïve background distribution but are of questionable biological relevance.Results: We describe a simple yet effective algorithm for discovering differential motifs between two sequence datasets that is effective in eliminating systematic biases and scalable to large datasets. Tested on 207 ENCODE ChIP-seq datasets, our method identifies correct motifs in 78% of the datasets with known motifs, demonstrating improvement in both accuracy and efficiency compared with DREME, another state-of-art discriminative motif discovery tool. More interestingly, on the remaining more challenging datasets, we identify common technical or biological factors that compromise the motif search results and use advanced features of our tool to control for these factors. We also present case studies demonstrating the ability of our method to detect single base pair differences in DNA specificity of two similar TFs. Lastly, we demonstrate discovery of key TF motifs involved in tissue specification by examination of high-throughput DNase accessibility data.Availability: The motifRG package is publically available via the bioconductor repository.

Original languageEnglish (US)
Pages (from-to)775-783
Number of pages9
JournalBioinformatics
Volume30
Issue number6
DOIs
StatePublished - Mar 2014
Externally publishedYes

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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  • Cite this

    Yao, Z., Macquarrie, K. L., Fong, A. P., Tapscott, S. J., Ruzzo, W. L., & Gentleman, R. C. (2014). Discriminative motif analysis of high-throughput dataset. Bioinformatics, 30(6), 775-783. https://doi.org/10.1093/bioinformatics/btt615