title: Romulus: robust multi-state identification of transcription factor binding sites from DNase-seq data.
abstract: Computational prediction of transcription factor (TF) binding sites in the genome remains a challenging task. Here, we present Romulus, a novel computational method for identifying individual TF binding sites from genome sequence information and cell-type-specific experimental data, such as DNase-seq. It combines the strengths of previous approaches, and improves robustness by reducing the number of free parameters in the model by an order of magnitude.
  
  
  
  We show that Romulus significantly outperforms existing methods across three sources of DNase-seq data, by assessing the performance of these tools against ChIP-seq profiles. The difference was particularly significant when applied to binding site prediction for low-information-content motifs. Our method is capable of inferring multiple binding modes for a single TF, which differ in their DNase I cut profile. Finally, using the model learned by Romulus and ChIP-seq data, we introduce Binding in Closed Chromatin (BCC) as a quantitative measure of TF pioneer factor activity. Uniquely, our measure quantifies a defining feature of pioneer factors, namely their ability to bind closed chromatin.
  
  
  
  Romulus is freely available as an R package at http://github.com/ajank/Romulus
  
  
  
  ajank@mimuw.edu.pl
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, 02-097 Warszawa, Poland Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Jankowski
authors.affiliation: Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, 02-097 Warszawa, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Tiuryn
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Shyam
authors.initials: S
authors.lastname: Prabhakar
mesh_terms: D001665:Binding Sites; D002843:Chromatin; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods*; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
chemical_list: D002843:Chromatin; D014157:Transcription Factors