Bacterial regulon modeling and prediction based on systematic cis regulatory motif analyses.
Bacterial regulon modeling and prediction based on systematic cis regulatory motif analyses.
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基于系统顺式调节基序分析的细菌调节子建模和预测
DOI：
10.1038/srep23030
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发表时间：
2016-03-15
影响因子：
4.6
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Liu B;Zhou C;Li G;Zhang H;Zeng E;Liu Q;Ma Q
调节子是细菌细胞应答系统的基本单位，每个调节子由一组转录共调控的操纵子组成。阐明调控子是研究细菌全局转录调控网络的基础。在这项研究中，我们设计了一个新的共调节评分一对操纵子之间的准确识别和顺式调控基序分析的基础上，它可以捕捉它们之间的共调节关系比其他分数更好。充分利用这一发现，我们开发了一个新的计算框架，并建立了一个新的图模型的调节子预测。该模型集成了模体比较和聚类，使调节子预测问题更加可解和准确。为了评估我们的预测，基于记录的调节子及其与我们的预测的重叠设计了调节子覆盖分数;并实施了修改的Fisher精确检验以测量我们的预测与源自E.在466种条件下收集的大肠杆菌微阵列基因表达数据集。结果表明，我们的程序在预测精度方面始终优于其他程序。这表明我们的算法大大提高了最先进的水平，从而使计算能力能够可靠地预测任何细菌的调节子。
Regulons are the basic units of the response system in a bacterial cell and each consists of a set of transcriptionally co-regulated operons. Regulon elucidation is the basis for studying the bacterial global transcriptional regulation network. In this study, we designed a novel co-regulation score between a pair of operons based on accurate operon identification and cis regulatory motif analyses, which can capture their co-regulation relationship much better than other scores. Taking full advantage of this discovery, we developed a new computational framework and built a novel graph model for regulon prediction. This model integrates the motif comparison and clustering and makes the regulon prediction problem substantially more solvable and accurate. To evaluate our prediction, a regulon coverage score was designed based on the documented regulons and their overlap with our prediction; and a modified Fisher Exact test was implemented to measure how well our predictions match the co-expressed modules derived from E. coli microarray gene-expression datasets collected under 466 conditions. The results indicate that our program consistently performed better than others in terms of the prediction accuracy. This suggests that our algorithms substantially improve the state-of-the-art, leading to a computational capability to reliably predict regulons for any bacteria.