Genome-wide de novo prediction of cis-regulatory binding sites in prokaryotes.

Genome-wide de novo prediction of cis-regulatory binding sites in prokaryotes.
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DOI:
10.1093/nar/gkp248
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发表时间:
2009-06
影响因子:
14.9
通讯作者:
Su Z
Su Z
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang S;Xu M;Li S;Su Z

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虽然顺式调控结合位点(CRBSs)在基因组中至少与编码序列一样重要,但由于缺乏高效、准确的实验和计算方法来表征它们,我们对它们在大多数测序基因组中的一般理解非常有限,这在很大程度上阻碍了我们对许多重要生物过程的理解。在本文中,我们描述了一种高精度的全基因组从头预测CRBSs的新算法。基于一种新的参考基因组选择方法、一种测量CRBS相似性的新度量和一种新的图聚类过程,我们设计了基于比较基因组学原理的CRBS预测算法,以克服三个已知的困难。当正确预测操纵子结构时,我们的算法可以预测大肠杆菌K12基因组中属于94%的已知顺式调控基序的81%的已知个体结合位点,同时具有很高的预测特异性。我们的算法在枯草芽孢杆菌基因组中也取得了类似的预测精度,这表明它非常稳健,因此可以应用于任何其他测序的原核生物基因组。与现有的先进算法相比,我们的算法在预测灵敏度和特异性方面都优于现有算法。
Although cis-regulatory binding sites (CRBSs) are at least as important as the coding sequences in a genome, our general understanding of them in most sequenced genomes is very limited due to the lack of efficient and accurate experimental and computational methods for their characterization, which has largely hindered our understanding of many important biological processes. In this article, we describe a novel algorithm for genome-wide de novo prediction of CRBSs with high accuracy. We designed our algorithm to circumvent three identified difficulties for CRBS prediction using comparative genomics principles based on a new method for the selection of reference genomes, a new metric for measuring the similarity of CRBSs, and a new graph clustering procedure. When operon structures are correctly predicted, our algorithm can predict 81% of known individual binding sites belonging to 94% of known cis-regulatory motifs in the Escherichia coli K12 genome, while achieving high prediction specificity. Our algorithm has also achieved similar prediction accuracy in the Bacillus subtilis genome, suggesting that it is very robust, and thus can be applied to any other sequenced prokaryotic genome. When compared with the prior state-of-the-art algorithms, our algorithm outperforms them in both prediction sensitivity and specificity.
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