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结核分枝杆菌开放阅读框上游序列中新型IdeR结合位点的计算预测与实验验证

Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames.

作者信息

Prakash Prachee, Yellaboina Sailu, Ranjan Akash, Hasnain Seyed E

机构信息

Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500 076, India.

出版信息

Bioinformatics. 2005 May 15;21(10):2161-6. doi: 10.1093/bioinformatics/bti375. Epub 2005 Mar 3.

DOI:10.1093/bioinformatics/bti375
PMID:15746274
Abstract

IdeR (iron-dependent regulator) is a key regulator of virulence factors and iron acquisition systems in Mycobacterium tuberculosis. Despite the wealth of information available on IdeR-regulated genes of M.tuberculosis, there is still an underlying possibility that there are novel genes/pathways that have gone undetected, the identification of which could give new insights into understanding the pathogenesis of M.tuberculosis. We describe an in silico approach employing the positional relative entropy method to identify potential IdeR binding sites in the upstream sequences of all the 3919 ORFs of M.tuberculosis. While many of the predictions made by this approach overlapped with the ones already identified by microarray experiments and binding assays, pointing to the accuracy of our method, a few genes for which there has been no evidence for IdeR regulation were additionally identified. Our results have implications on the iron-dependent regulatory mechanism of M.tuberculosis vis-a-vis the activity of urease operon and novel transcription regulators and transporters.

摘要

IdeR(铁依赖性调节因子)是结核分枝杆菌毒力因子和铁获取系统的关键调节因子。尽管关于结核分枝杆菌中IdeR调控基因已有大量信息,但仍存在未被发现的新基因/途径的潜在可能性,鉴定这些基因/途径可能为理解结核分枝杆菌的发病机制提供新的见解。我们描述了一种利用位置相对熵方法的计算机方法,以识别结核分枝杆菌3919个开放阅读框(ORF)上游序列中的潜在IdeR结合位点。虽然该方法做出的许多预测与通过微阵列实验和结合测定已鉴定出的预测重叠,表明我们方法的准确性,但额外鉴定出了一些尚无IdeR调控证据的基因。我们的结果对结核分枝杆菌的铁依赖性调节机制与脲酶操纵子以及新型转录调节因子和转运蛋白的活性具有启示意义。

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