TY - JOUR A1 - Rozowsky, Joel S. A1 - Newburger, Daniel A1 - Sayward, Fred A1 - Wu, Jiaqian A1 - Jordan, Greg A1 - Korbel, Jan O. A1 - Nagalakshmi, Ugrappa A1 - Yang, Jin A1 - Zheng, Deyou A1 - Guigó, Roderic A1 - Gingeras, Thomas R. A1 - Weissman, Sherman A1 - Miller, Perry A1 - Snyder, Michael A1 - Gerstein, Mark B. T1 - The DART classification of unannotated transcription within the ENCODE regions: Associating transcription with known and novel loci Y1 - 2007/06/01 JF - Genome Research JO - Genome Research SP - 732 EP - 745 DO - 10.1101/gr.5696007 VL - 17 IS - 6 UR - http://genome.cshlp.org/content/17/6/732.abstract N2 - 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. ER -