Evaluation of methods for modeling transcription factor sequence specificity

Weirauch, Matthew T. and Cote, Atina and Norel, Raquel and Annala, Matti and Zhao, Yue and Riley, Todd R. and Saez-Rodriguez, Julio and Cokelaer, Thomas and Vedenko, Anastasia and Talukder, Shaheynoor and Bussemaker, Harmen J. and Morris, Quaid D. and Bulyk, Martha L. and Stolovitzky, Gustavo and Hughes, Timothy R.. (2013) Evaluation of methods for modeling transcription factor sequence specificity. Nature biotechnology, Vol. 31, H. 2. pp. 126-134.

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Official URL: http://edoc.unibas.ch/dok/A6124560

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Genomic analyses often involve scanning for potential transcription factor (TF) binding sites using models of the sequence specificity of DNA binding proteins. Many approaches have been developed to model and learn a protein's DNA-binding specificity, but these methods have not been systematically compared. Here we applied 26 such approaches to in vitro protein binding microarray data for 66 mouse TFs belonging to various families. For nine TFs, we also scored the resulting motif models on in vivo data, and found that the best in vitro-derived motifs performed similarly to motifs derived from the in vivo data. Our results indicate that simple models based on mononucleotide position weight matrices trained by the best methods perform similarly to more complex models for most TFs examined, but fall short in specific cases (>10% of the TFs examined here). In addition, the best-performing motifs typically have relatively low information content, consistent with widespread degeneracy in eukaryotic TF sequence preferences.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Bioinformatics (Schmid)
UniBasel Contributors:Schmid, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Aug 2013 07:35
Deposited On:16 Aug 2013 07:34

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