FITBAR: a web tool for the robust prediction of prokaryotic regulons.

FITBAR: a web tool for the robust prediction of prokaryotic regulons.
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DOI:
10.1186/1471-2105-11-554
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发表时间:
2010-11-11
期刊:
影响因子:
3
通讯作者:
Oberto J
Oberto J
中科院分区:
生物学4区
文献类型:
--
作者:
Oberto J

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调控蛋白与其特异性DNA靶点的结合决定了邻近基因的准确表达。完全测序的基因组中新结合位点的计算机预测是深入理解基因调控网络的一个关键方面。已经描述了几种算法来区分新的结合靶标的预测中的假阳性;然而,到目前为止,它们中没有一个被实施来帮助在基因组规模上检测结合位点。FITBAR(细菌和大肠杆菌调节子快速调查工具)是一个网络服务,旨在确定完全测序的原核基因组上的新蛋白质结合位点。该工具包含一个工作台,可以使用不同的统计方法比较预测的重要性,这是现有资源中没有的功能。已实施局部马尔可夫模型和复合重要性抽样算法来计算新发现的结合位点的P值。此外,FITBAR提供了两种优化的基因组扫描算法,使用对数优势或熵加权位置特异性评分矩阵。其他重要功能包括为每个检测到的结合位点生成详细的基因组背景图,并以电子表格和便携式文档格式导出搜索结果。FITBAR发现了一个高亲和力的大肠杆菌NagC结合位点,并在体外和体内进行了实验验证和发表。FITBAR的开发是为了快速、准确且统计上稳健地预测原核调节子。这一特点构成了该网络工具相对于其他矩阵搜索程序的主要优势,并且不会损害其性能。该网络服务可在http://archaea.u-psud.fr/fitbar上获得。
The binding of regulatory proteins to their specific DNA targets determines the accurate expression of the neighboring genes. The in silico prediction of new binding sites in completely sequenced genomes is a key aspect in the deeper understanding of gene regulatory networks. Several algorithms have been described to discriminate against false-positives in the prediction of new binding targets; however none of them has been implemented so far to assist the detection of binding sites at the genomic scale. FITBAR (Fast Investigation Tool for Bacterial and Archaeal Regulons) is a web service designed to identify new protein binding sites on fully sequenced prokaryotic genomes. This tool consists in a workbench where the significance of the predictions can be compared using different statistical methods, a feature not found in existing resources. The Local Markov Model and the Compound Importance Sampling algorithms have been implemented to compute the P-value of newly discovered binding sites. In addition, FITBAR provides two optimized genomic scanning algorithms using either log-odds or entropy-weighted position-specific scoring matrices. Other significant features include the production of a detailed genomic context map for each detected binding site and the export of the search results in spreadsheet and portable document formats. FITBAR discovery of a high affinity Escherichia coli NagC binding site was validated experimentally in vitro as well as in vivo and published. FITBAR was developed in order to allow fast, accurate and statistically robust predictions of prokaryotic regulons. This feature constitutes the main advantage of this web tool over other matrix search programs and does not impair its performance. The web service is available at http://archaea.u-psud.fr/fitbar.
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