title: The DART classification of unannotated transcription within the ENCODE regions: associating transcription with known and novel loci.
abstract: For the approximately 1% of the human genome in the ENCODE regions, only about half of the transcriptionally active regions (TARs) identified with tiling microarrays correspond to annotated exons. Here we categorize this large amount of "unannotated transcription." We use a number of disparate features to classify the 6988 novel TARs-array expression profiles across cell lines and conditions, sequence composition, phylogenetic profiles (presence/absence of syntenic conservation across 17 species), and locations relative to genes. In the classification, we first filter out TARs with unusual sequence composition and those likely resulting from cross-hybridization. We then associate some of those remaining with proximal exons having correlated expression profiles. Finally, we cluster unclassified TARs into putative novel loci, based on similar expression and phylogenetic profiles. To encapsulate our classification, we construct a Database of Active Regions and Tools (DART.gersteinlab.org). DART has special facilities for rapidly handling and comparing many sets of TARs and their heterogeneous features, synchronizing across builds, and interfacing with other resources. Overall, we find that approximately 14% of the novel TARs can be associated with known genes, while approximately 21% can be clustered into approximately 200 novel loci. We observe that TARs associated with genes are enriched in the potential to form structural RNAs and many novel TAR clusters are associated with nearby promoters. To benchmark our classification, we design a set of experiments for testing the connectivity of novel TARs. Overall, we find that 18 of the 46 connections tested validate by RT-PCR and four of five sequenced PCR products confirm connectivity unambiguously.
authors.affiliation: Molecular Biophysics and Biochemistry Department, Yale University, New Haven, Connecticut 06520-8114, USA. joel.rozowsky@yale.edu
authors.forename: Joel S
authors.initials: JS
authors.lastname: Rozowsky
authors.forename: Daniel
authors.initials: D
authors.lastname: Newburger
authors.forename: Fred
authors.initials: F
authors.lastname: Sayward
authors.forename: Jiaqian
authors.initials: J
authors.lastname: Wu
authors.forename: Greg
authors.initials: G
authors.lastname: Jordan
authors.forename: Jan O
authors.initials: JO
authors.lastname: Korbel
authors.forename: Ugrappa
authors.initials: U
authors.lastname: Nagalakshmi
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gingeras
authors.forename: Sherman
authors.initials: S
authors.lastname: Weissman
authors.forename: Perry
authors.initials: P
authors.lastname: Miller
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D015894:Genome, Human / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D040641:Quantitative Trait Loci / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology*