Journal
NUCLEIC ACIDS RESEARCH
Volume 40, Issue 15, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gks543
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Funding
- Research Foundation Flanders (FWO) [G.0704.11N]
- University of Leuven [CREA/10/014, PF/10/016]
- Human Frontiers Science Program (HFSP) [RGY0070/2011]
- Foundation Against Cancer [2010-154]
- Vlaamse Liga tegen Kanker
- Research Foundation Flanders [G.0704.11N]
- ANR-ERASysBio+
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The field of regulatory genomics today is characterized by the generation of high-throughput data sets that capture genome-wide transcription factor (TF) binding, histone modifications, or DNAseI hypersensitive regions across many cell types and conditions. In this context, a critical question is how to make optimal use of these publicly available datasets when studying transcriptional regulation. Here, we address this question in Drosophila melanogaster for which a large number of high-throughput regulatory datasets are available. We developed i-cisTarget (where the 'i' stands for integrative), for the first time enabling the discovery of different types of enriched 'regulatory features' in a set of co-regulated sequences in one analysis, being either TF motifs or 'in vivo' chromatin features, or combinations thereof. We have validated our approach on 15 co-expressed gene sets, 21 ChIP data sets, 628 curated gene sets and multiple individual case studies, and show that meaningful regulatory features can be confidently discovered; that bona fide enhancers can be identified, both by in vivo events and by TF motifs; and that combinations of in vivo events and TF motifs further increase the performance of enhancer prediction.
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