|Title||Epigenetic priors for identifying active transcription factor binding sites. |
|Publication Type||Journal Article |
|Year of Publication||2012 |
|Authors||Cuellar-Partida G, Buske FA, McLeay RC, Whitington T, Noble W S, Bailey TL |
|Journal||Bioinformatics (Oxford, England) |
|Date or Month Published||2012 Jan 1 |
|Abstract||MOTIVATION: Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored.
RESULTS: We describe a probabilistic method for combining one or more tracks of epigenetic data with a standard DNA sequence motif model to improve our ability to identify active transcription factor binding sites (TFBSs). We convert each data type into a position-specific probabilistic prior and combine these priors with a traditional probabilistic motif model to compute a log-posterior odds score. Our experiments, using histone modifications H3K4me1, H3K4me3, H3K9ac and H3K27ac, as well as DNase I sensitivity, show conclusively that the log-posterior odds score consistently outperforms a simple binary filter based on the same data. We also show that our approach performs competitively with a more complex method, CENTIPEDE, and suggest that the relative simplicity of the log-posterior odds scoring method makes it an appealing and very general method for identifying functional TFBSs on the basis of DNA and epigenetic evidence. AVAILABILITY AND IMPLEMENTATION: FIMO, part of the MEME Suite software toolkit, now supports log-posterior odds scoring using position-specific priors for motif search. A web server and source code are available at http://meme.nbcr.net. Utilities for creating priors are at http://research.imb.uq.edu.au/t.bailey/SD/Cuellar2011.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. |
|Alternate Journal||Bioinformatics |
|Citation Key||7853 |
|PubMed ID||22072382 |