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DNA Research Advance Access originally published online on September 9, 2009
DNA Research 2009 16(5):261-273; doi:10.1093/dnares/dsp014
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© The Author 2009. Published by Oxford University Press on behalf of Kazusa DNA Research Institute
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Exhaustive Search for Over-represented DNA Sequence Motifs with CisFinder

Alexei A. Sharov and Minoru S.H. Ko*

Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA

Received 16 May 2009 ; accepted 27 July 2009.

We present CisFinder software, which generates a comprehensive list of motifs enriched in a set of DNA sequences and describes them with position frequency matrices (PFMs). A new algorithm was designed to estimate PFMs directly from counts of n-mer words with and without gaps; then PFMs are extended over gaps and flanking regions and clustered to generate non-redundant sets of motifs. The algorithm successfully identified binding motifs for 12 transcription factors (TFs) in embryonic stem cells based on published chromatin immunoprecipitation sequencing data. Furthermore, CisFinder successfully identified alternative binding motifs of TFs (e.g. POU5F1, ESRRB, and CTCF) and motifs for known and unknown co-factors of genes associated with the pluripotent state of ES cells. CisFinder also showed robust performance in the identification of motifs that were only slightly enriched in a set of DNA sequences.

Key words: algorithm; software; transcription factor binding site; ChIP-seq; embryonic stem cells

* To whom correspondence should be addressed. Tel. +1 410-558-8359. Fax. +1 410-558-8331. E-mail: kom{at}mail.nih.gov


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