A discriminative model for identifying spatial cis-regulatory modules

A discriminative model for identifying spatial cis-regulatory modules
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识别空间顺式调控模块的判别模型

DOI:
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发表时间:
2004
期刊:
J. Comput. Biol.
影响因子:
--
通讯作者:
R. Sharan
R. Sharan
中科院分区:
--
文献类型:
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作者:
E. Segal;R. Sharan

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转录调控是通过转录因子与基因上游区域的协同结合来介导的。在高等真核生物中,协作转录因子的结合位点被组织成短序列单元,称为顺式调控模块。在本文中,我们提出了一种方法来确定模块的转录因子结合位点的一组共调节基因,仅使用原始序列数据作为输入。我们的方法是基于一种新的概率模型,描述了顺式调控的机制,包括合作转录因子的结合位点,这些结合位点的组织成短序列模块,和基因的调控其模块。我们表明,我们的方法是成功的发现种植模块在模拟数据和已知的模块在酵母。更重要的是,我们将我们的方法应用于大量的人类基因集,发现了83个重要的顺式调控模块,其中包括36个已知的模体和许多新的。因此,我们的研究结果提供了第一个全面的纲要推定顺式调节模块在人类。
Transcriptional regulation is mediated by the coordinated binding of transcription factors to the upstream region of genes. In higher eukaryotes, the binding sites of cooperating transcription factors are organized into short sequence units, called cis-regulatory modules. In this paper we propose a method for identifying modules of transcription factor binding sites in a set of co-regulated genes, using only the raw sequence data as input. Our method is based on a novel probabilistic model that describes the mechanism of cis-regulation, including the binding sites of cooperating transcription factors, the organization of these binding sites into short sequence modules, and the regulation of a gene by its modules. We show that our method is successful in discovering planted modules in simulated data and known modules in yeast. More importantly, we applied our method to a large collection of human gene sets, and found 83 significant cis-regulatory modules, which included 36 known motifs and many novel ones. Thus, our results provide one of the first comprehensive compendiums of putative cis-regulatory modules in human.
DOI: 10.1006/jmbi.1998.1700
发表时间: 1998-04-24
影响因子: 5.6
作者:
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通讯作者: Fickett, JW
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