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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents



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ID: 539117.0, MPI für molekulare Genetik / Research Group Development and Disease
Integrative analysis of genomic, functional and protein interaction data predicts long-range enhancer-target gene interactions.
Authors:Rödelsperger, C.; Guo, G.; Kolanczyk, M.; Pletschacher, A.; Köhler, S.; Bauer, S.; Schulz, M. H.; Robinson, P. N.
Language:English
Date of Publication (YYYY-MM-DD):2010-11-24
Title of Journal:Nucleic Acids Research
Journal Abbrev.:Nucleic Acids Res
Volume:24
Issue / Number:2
Start Page:1
End Page:11
Copyright:© 2010 Oxford University Press
Review Status:not specified
Audience:Experts Only
Abstract / Description:Multicellular organismal development is controlled by a complex network of transcription factors, promoters and enhancers. Although reliable computational and experimental methods exist for enhancer detection, prediction of their target genes remains a major challenge. On the basis of available literature and ChIP-seq and ChIP-chip data for enhanceosome factor p300 and the transcriptional regulator Gli3, we found that genomic proximity and conserved synteny predict target genes with a relatively low recall of 12-27% within 2 Mb intervals centered at the enhancers. Here, we show that functional similarities between enhancer binding proteins and their transcriptional targets and proximity in the protein-protein interactome improve prediction of target genes. We used all four features to train random forest classifiers that predict target genes with a recall of 58% in 2 Mb intervals that may contain dozens of genes, representing a better than two-fold improvement over the performance of prediction based on single features alone. Genome-wide ChIP data is still relatively poorly understood, and it remains difficult to assign biological significance to binding events. Our study represents a first step in integrating various genomic features in order to elucidate the genomic network of long-range regulatory interactions.
Comment of the Author/Creator:To whom correspondence should be addressed:
Tel: +49 30 450566042; Fax: +49 30 450569915;
Email: peter.robinson@charite.de
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany;
2.Institute for Medical Genetics, Charité-Universitätsmedizin, Berlin, Germany.
Identifiers:ISSN:0305-1048 [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/21109530 [ID No:2]
DOI:10.1093/nar/gkq1081 [ID No:3]
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