Title
Romulus: robust multi-state identification of transcription factor binding sites from DNase-seq data.
Abstract
Motivation: 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. Results: 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.
Year
DOI
Venue
2016
10.1093/bioinformatics/btw209
BIOINFORMATICS
Field
DocType
Volume
Genome,Data mining,Binding site,DNA binding site,Computer science,Robustness (computer science),DNase-Seq,Bioinformatics,Chromatin immunoprecipitation,Chromatin,Pioneer factor
Journal
32
Issue
ISSN
Citations 
16
1367-4803
3
PageRank 
References 
Authors
0.41
3
3
Name
Order
Citations
PageRank
Aleksander Jankowski1343.47
Jerzy Tiuryn21210126.00
Shyam Prabhakar330.74