Evaluation of methods for modeling transcription factor sequence specificity.
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.
Banting and Best Department of Medical Research and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Matthew T
MT
Weirauch
Atina
A
Cote
Raquel
R
Norel
Matti
M
Annala
Yue
Y
Zhao
Todd R
TR
Riley
Julio
J
Saez-Rodriguez
Thomas
T
Cokelaer
Anastasia
A
Vedenko
Shaheynoor
S
Talukder
Harmen J
HJ
Bussemaker
Quaid D
QD
Morris
Martha L
ML
Bulyk
Gustavo
G
Stolovitzky
Timothy R
TR
Hughes
D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D016678:Genome; D051379:Mice; D059372:Nucleotide Motifs / Q000235:genetics*; D056510:Position-Specific Scoring Matrices; D040081:Protein Array Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D014157:Transcription Factors