title: RFECS: a random-forest based algorithm for enhancer identification from chromatin state.
abstract: Transcriptional enhancers play critical roles in regulation of gene expression, but their identification in the eukaryotic genome has been challenging. Recently, it was shown that enhancers in the mammalian genome are associated with characteristic histone modification patterns, which have been increasingly exploited for enhancer identification. However, only a limited number of cell types or chromatin marks have previously been investigated for this purpose, leaving the question unanswered whether there exists an optimal set of histone modifications for enhancer prediction in different cell types. Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. We show that RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction.
authors.affiliation: Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Nisha
authors.initials: N
authors.lastname: Rajagopal
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Uli
authors.initials: U
authors.lastname: Wagner
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Stamatoyannopoulos
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D003663:Decision Trees; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors