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

Joel S. Rozowsky, Daniel Newburger, Fred Sayward, Jiaqian Wu, Greg Jordan, Jan O. Korbel, Ugrappa Nagalakshmi, Jin Yang, Deyou Zheng, Roderic Guigó, Thomas R. Gingeras, Sherman Weissman, Perry Miller, Michael Snyder, Mark B. Gerstein

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

For the ∼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 ∼14% of the novel TARs can be associated with known genes, while ∼21% can be clustered into ∼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.

Original languageEnglish (US)
Pages (from-to)732-745
Number of pages14
JournalGenome research
Volume17
Issue number6
DOIs
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'The DART classification of unannotated transcription within the ENCODE regions: Associating transcription with known and novel loci'. Together they form a unique fingerprint.

  • Cite this

    Rozowsky, J. S., Newburger, D., Sayward, F., Wu, J., Jordan, G., Korbel, J. O., Nagalakshmi, U., Yang, J., Zheng, D., Guigó, R., Gingeras, T. R., Weissman, S., Miller, P., Snyder, M., & Gerstein, M. B. (2007). The DART classification of unannotated transcription within the ENCODE regions: Associating transcription with known and novel loci. Genome research, 17(6), 732-745. https://doi.org/10.1101/gr.5696007