Journal
BIOINFORMATICS
Volume 30, Issue 22, Pages 3143-3151Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btu519
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Funding
- Interdisciplinary Center for Clinical Research (IZKF Aachen)
- Brazilian research agency FACEPE
- Brazilian research agency CNPq
- RWTH Aachen University Medical School, Aachen, Germany
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Motivation: The identification of active transcriptional regulatory elements is crucial to understand regulatory networks driving cellular processes such as cell development and the onset of diseases. It has recently been shown that chromatin structure information, such as DNase I hypersensitivity (DHS) or histone modifications, significantly improves cell-specific predictions of transcription factor binding sites. However, no method has so far successfully combined both DHS and histone modification data to perform active binding site prediction. Results: We propose here a method based on hidden Markov models to integrate DHS and histone modifications occupancy for the detection of open chromatin regions and active binding sites. We have created a framework that includes treatment of genomic signals, model training and genome-wide application. In a comparative analysis, our method obtained a good trade-off between sensitivity versus specificity and superior area under the curve statistics than competing methods. Moreover, our technique does not require further training or sequence information to generate binding location predictions. Therefore, the method can be easily applied on new cell types and allow flexible downstream analysis such as de novo motif finding.
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