title: Accurate Promoter and Enhancer Identification in 127 ENCODE and Roadmap Epigenomics Cell Types and Tissues by GenoSTAN.
abstract: Accurate maps of promoters and enhancers are required for understanding transcriptional regulation. Promoters and enhancers are usually mapped by integration of chromatin assays charting histone modifications, DNA accessibility, and transcription factor binding. However, current algorithms are limited by unrealistic data distribution assumptions. Here we propose GenoSTAN (Genomic STate ANnotation), a hidden Markov model overcoming these limitations. We map promoters and enhancers for 127 cell types and tissues from the ENCODE and Roadmap Epigenomics projects, today's largest compendium of chromatin assays. Extensive benchmarks demonstrate that GenoSTAN generally identifies promoters and enhancers with significantly higher accuracy than previous methods. Moreover, GenoSTAN-derived promoters and enhancers showed significantly higher enrichment of complex trait-associated genetic variants than current annotations. Altogether, GenoSTAN provides an easy-to-use tool to define promoters and enhancers in any system, and our annotation of human transcriptional cis-regulatory elements constitutes a rich resource for future research in biology and medicine.
authors.affiliation: Gene Center and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität Munich, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Zacher
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Margaux
authors.initials: M
authors.lastname: Michel
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Schwalb
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
authors.affiliation: Department of Biology, University of Cologne, Cologne, Germany.|Max Planck Institute for Plant Breeding Research, Cologne, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Tresch
authors.affiliation: Gene Center and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität Munich, Germany.
authors.forename: Julien
authors.identifier: http://orcid.org/0000-0002-8924-8365
authors.initials: J
authors.lastname: Gagneur
mesh_terms: D000465:Algorithms; D002843:Chromatin / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones