The DART classification of unannotated transcription within the ENCODE regions: Associating transcription with known and novel loci

  • Rozowsky J
  • Newburger D
  • Sayward F
 et al. 
  • 83

    Readers

    Mendeley users who have this article in their library.
  • 21

    Citations

    Citations of this article.

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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Joel S. Rozowsky

  • Daniel Newburger

  • Fred Sayward

  • Jiaqian Wu

  • Greg Jordan

  • Jan O. Korbel

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free