GREAT improves functional interpretation of cis-regulatory regions.
GREAT improves functional interpretation of cis-regulatory regions.
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DOI：
10.1038/nbt.1630
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发表时间：
2010-05
影响因子：
46.9
通讯作者：
Bejerano G
中科院分区：
文献类型：
--
作者：
McLean CY;Bristor D;Hiller M;Clarke SL;Schaar BT;Lowe CB;Wenger AM;Bejerano G
我们开发了基因组区域富集注释工具（GREAT），以分析通过整个基因组的DNA结合事件的局部测量确定的顺式调控区域的功能意义。虽然以前的方法只考虑了与基因近端的结合，但GREAT能够正确地结合远端结合位点，并使用对输入基因组区域的二项式检验来控制假阳性。GREAT整合了来自20个本体的注释，并可作为网络应用程序使用。将GREAT应用于多个转录相关因子（包括SRF，NRSF，GABP，Stat 3和p300）的染色质免疫沉淀结合大规模并行测序（ChIP-seq）的数据集，我们恢复了现有基于基因的工具所遗漏的这些因子的许多功能，并生成了可检验的假设。GREAT的实用性不仅限于ChIP-seq，因为它还可以应用于开放染色质，局部表观基因组标记和类似的功能数据集，以及比较基因组学集。
We developed the Genomic Regions Enrichment of Annotations Tool (GREAT) to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions. GREAT incorporates annotations from 20 ontologies and is available as a web application. Applying GREAT to data sets from chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) of multiple transcription-associated factors, including SRF, NRSF, GABP, Stat3 and p300 in different developmental contexts, we recover many functions of these factors that are missed by existing gene-based tools, and we generate testable hypotheses. The utility of GREAT is not limited to ChIP-seq, as it could also be applied to open chromatin, localized epigenomic markers and similar functional data sets, as well as comparative genomics sets.