title: Predicting DNA-binding specificities of eukaryotic transcription factors.
abstract: Today, annotated amino acid sequences of more and more transcription factors (TFs) are readily available. Quantitative information about their DNA-binding specificities, however, are hard to obtain. Position frequency matrices (PFMs), the most widely used models to represent binding specificities, are experimentally characterized only for a small fraction of all TFs. Even for some of the most intensively studied eukaryotic organisms (i.e., human, rat and mouse), roughly one-sixth of all proteins with annotated DNA-binding domain have been characterized experimentally. Here, we present a new method based on support vector regression for predicting quantitative DNA-binding specificities of TFs in different eukaryotic species. This approach estimates a quantitative measure for the PFM similarity of two proteins, based on various features derived from their protein sequences. The method is trained and tested on a dataset containing 1 239 TFs with known DNA-binding specificity, and used to predict specific DNA target motifs for 645 TFs with high accuracy.
authors.affiliation: Center for Bioinformatics Tübingen (ZBIT), University of Tübingen, Tübingen, Germany. adrian.schroeder@uni-tuebingen.de
authors.forename: Adrian
authors.initials: A
authors.lastname: Schröder
authors.forename: Johannes
authors.initials: J
authors.lastname: Eichner
authors.forename: Jochen
authors.initials: J
authors.lastname: Supper
authors.forename: Jonas
authors.initials: J
authors.lastname: Eichner
authors.forename: Dierk
authors.initials: D
authors.lastname: Wanke
authors.forename: Carsten
authors.initials: C
authors.lastname: Henneges
authors.forename: Andreas
authors.initials: A
authors.lastname: Zell
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D019295:Computational Biology / Q000379:methods; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA