Evaluation of methods for modeling transcription factor sequence specificity Journal Article


Authors: Weirauch, M. T.; Cote, A.; Norel, R.; Annala, M.; Zhao, Y.; Riley, T. R.; Saez-Rodriguez, J.; Cokelaer, T.; Vedenko, A.; Talukder, S.; Bussemaker, H. J.; Quaid, M. D.; Bulyk, M. L.; Stolovitzky, G.; Hughes, T. R.; Agius, P.; Arvey, A.; Bucher, P.; Callan, C. G. Jr; Chang, C. W.; Chen, C. Y.; Chen, Y. S.; Chu, Y. W.; Grau, J.; Grosse, I.; Jagannathan, V.; Keilwagen, J.; Kiebasa, S. M.; Kinney, J. B.; Klein, H.; Kursa, M. B.; Lähdesmäki, H.; Laurila, K.; Lei, C.; Leslie, C.; Linhart, C.; Murugan, A.; Myšičková, A.; Noble, W. S.; Nykter, M.; Orenstein, Y.; Posch, S.; Ruan, J.; Rudnicki, W. R.; Schmid, C. D.; Shamir, R.; Sung, W. K.; Vingron, M.; Zhang, Z.
Article Title: Evaluation of methods for modeling transcription factor sequence specificity
Abstract: 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. © 2013 Nature America, Inc. All rights reserved.
Journal Title: Nature Biotechnology
Volume: 31
Issue: 2
ISSN: 1087-0156
Publisher: Nature Publishing Group  
Date Published: 2013-01-27
Start Page: 126
End Page: 134
Language: English
DOI: 10.1038/nbt.2486
PROVIDER: scopus
PUBMED: 23354101
PMCID: PMC3687085
DOI/URL:
Notes: --- - "Export Date: 1 March 2013" - "CODEN: NABIF" - "Source: Scopus"
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  1. Christina Leslie
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  2. Phaedra Agius
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  3. Aaron J. Arvey
    20 Arvey