Predicting tissue specific transcription factor binding sites.
BACKGROUND
Studies of gene regulation often utilize genome-wide predictions of transcription factor (TF) binding sites. Most existing prediction methods are based on sequence information alone, ignoring biological contexts such as developmental stages and tissue types. Experimental methods to study in vivo binding, including ChIP-chip and ChIP-seq, can only study one transcription factor in a single cell type and under a specific condition in each experiment, and therefore cannot scale to determine the full set of regulatory interactions in mammalian transcriptional regulatory networks.


RESULTS
We developed a new computational approach, PIPES, for predicting tissue-specific TF binding. PIPES integrates in vitro protein binding microarrays (PBMs), sequence conservation and tissue-specific epigenetic (DNase I hypersensitivity) information. We demonstrate that PIPES improves over existing methods on distinguishing between in vivo bound and unbound sequences using ChIP-seq data for 11 mouse TFs. In addition, our predictions are in good agreement with current knowledge of tissue-specific TF regulation.


CONCLUSIONS
We provide a systematic map of computationally predicted tissue-specific binding targets for 284 mouse TFs across 55 tissue/cell types. Such comprehensive resource is useful for researchers studying gene regulation.
Shan
S
Zhong
Xin
X
He
Lane Center for Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, 15213, USA. zivbj@cs.cmu.edu.
Ziv
Z
Bar-Joseph
D000818:Animals; D001665:Binding Sites / Q000235:genetics*; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification; D003850:Deoxyribonuclease I / Q000235:genetics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics*; D016678:Genome; D006657:Histones / Q000235:genetics; D051379:Mice; D009928:Organ Specificity; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification
D004268:DNA-Binding Proteins; D006657:Histones; D014157:Transcription Factors; D003850:Deoxyribonuclease I