Inferring direct DNA binding from ChIP-seq

By Timothy L. Bailey, Philip Machanick. Nucleic Acids Research, 2012

468 citations recorded by the source corpus.

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 http://meme.nbcr.net. All data and output files presented here are available at: http://research.imb.uq.edu.au/t.bailey/sd/Bailey2011a.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d1619ff58ade467139a6f6eb0cb0dfbeac181dda

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Citations in the corpus

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles (2015, methodology): “Following the process used for PFMs derived from ChIPseq data in the previous JASPAR release (13), we curated the TFFMs by using a centrality P-value as described in (25) as one expects predicted TFBSs to be enriched at the position where the maximum amount of reads mapped in the ChIP-seq peaks.”
JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles (2013, methodology): “As part of the curation of ChIP-seq data, and as introduced earlier, we computed a centrality score as described in (20), based on our expectation that the positions where the maximum number of ChIP-seq reads map on the genome of reference will be strongly enriched for binding sites corresponding to”
Distinct structural bases for sequence-specific DNA binding by mammalian BEN domain proteins (2022, unknown): “In particular, de novo motif finding using DREME (Bailey 2011) and Cen-triMo (Bailey and Machanick 2012) showed that top hits, in terms of both significance and frequency, closely resembled the BD4 PBM site (Fig.”
A comparative analysis of transcription factor binding models learned from PBM, HT-SELEX and ChIP data (2014, background): “The recent observation that E2F1 and Smad1 ChIP-seq peaks do not contain the in vitro binding site (22) may explain the failures for E2F and Smad3.”
A protocol for RNA methylation differential analysis with MeRIP-Seq data and exomePeak R/Bioconductor package. (2014, background): “The motif occurrence is reported centrally enriched (p-value 8.3e-3) by CentriMo [40] (Figure 5), indicates it is the consensus sequence targeted by RNA-binding domains (RBDs) of RNA methyltransferases, such as, METTL3 and METTL14 [41], in post-transcriptional regulation process.”
The MEME Suite (2015, methodology): “The sequences input to CentriMo must all have the same length, which is not the case with the less sensitive motif enrichment algorithm AME.”