Inferring direct DNA binding from ChIP-seq

Bailey, Timothy L. and Machanick, P. (2012) Inferring direct DNA binding from ChIP-seq. Nucleic Acids Research, 40 17: e128-1-e128-10. doi:10.1093/nar/gks433

Author Bailey, Timothy L.
Machanick, P.
Title Inferring direct DNA binding from ChIP-seq
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
Publication date 2012-09
Sub-type Article (original research)
DOI 10.1093/nar/gks433
Open Access Status DOI
Volume 40
Issue 17
Start page e128-1
End page e128-10
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2013
Language eng
Formatted abstract
Genome-wide binding data from transcription factor ChIP-seq experiments is the best source of information for inferring the relative DNA-binding affinity of these proteins in vivo. However, standard motif enrichment analysis and motif discovery approaches sometimes fail to correctly identify the binding motif for the ChIP-ed factor. To overcome this problem, we propose ‘central motif enrichment analysis’ (CMEA), which is based on the observation that the positional distribution of binding sites matching the direct-binding motif tends to be unimodal, well centered and maximal in the precise center of the ChIP-seq peak regions. We describe a novel visualization and statistical analysis tool—CentriMo—that identifies the region of maximum central enrichment in a set of ChIP-seq peak regions and displays the positional distributions of predicted sites. Using CentriMo for motif enrichment analysis, we provide evidence that one transcription factor (Nanog) has different binding affinity in vivo than in vitro, that another binds DNA cooperatively (E2f1), and confirm the in vivo affinity of NFIC, rescuing a difficult ChIP-seq data set. In another data set, CentriMo strongly suggests that there is no evidence of direct DNA binding by the ChIP-ed factor (Smad1). CentriMo is now part of the MEME Suite software package available at All data and output files presented here are available at:
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online: May 18, 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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Created: Fri, 03 Aug 2012, 09:42:40 EST by Susan Allen on behalf of Institute for Molecular Bioscience