The DART classification of unannotated transcription within the ENCODE regions: associating transcription with known and novel loci.
The DART classification of unannotated transcription within the ENCODE regions: associating transcription with known and novel loci.
复制标题
ENCODE 区域内未注释转录的 DART 分类：将转录与已知和新基因座关联。
DOI：
10.1101/gr.5696007
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发表时间：
2007
期刊：
影响因子：
7
通讯作者：
Gerstein,MarkB
中科院分区：
文献类型：
--
作者：
Rozowsky,JoelS;Newburger,Daniel;Sayward,Fred;Wu,Jiaqian;Jordan,Greg;Korbel,JanO;Nagalakshmi,Ugrappa;Yang,Jin;Zheng,Deyou;Guigó,Roderic;Gingeras,ThomasR;Weissman,Sherman;Miller,Perry;Snyder,Michael;Gerstein,MarkB
对于ENCODE区域中人类基因组的∼1%，用平铺微阵列鉴定的转录活性区域(TAR)中只有大约一半对应于注释外显子。在这里，我们将这些大量的“未加注释的转录”归类。我们使用许多不同的特征来分类6988个新的TARS阵列表达谱，包括细胞系和条件、序列组成、系统发育谱(17个物种是否存在同线保守)以及与基因相关的位置。在分类中，我们首先筛选出序列组成不寻常的焦油和可能由杂交产生的焦油。然后，我们将一些剩余的外显子与具有相关表达谱的近端外显子联系起来。最后，我们根据相似的表达和系统发育图谱，将未分类的TAR聚类到可能的新基因座。为了封装我们的分类，我们构建了一个活动区域和工具数据库(DART.gersteinlab.org)。DART具有特殊的设施，用于快速处理和比较多组TAR及其异类功能、跨内部版本同步以及与其他资源接口。总体而言，我们发现∼14%的新TAR可以与已知基因相关联，而∼21%可以聚集到∼200新的基因座中。我们观察到与基因相关的TAR富含形成结构RNA的潜力，许多新的TAR簇与附近的启动子相关。为了对我们的分类进行基准测试，我们设计了一组实验来测试新型TAR的连通性。总体而言，我们发现，在测试的46个连接中，有18个通过RT-PCR验证，5个测序的PCR产物中有4个明确地确认了连接性。
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.