MARZ: an algorithm to combinatorially analyze gapped n-mer models of transcription factor binding.

MARZ: an algorithm to combinatorially analyze gapped n-mer models of transcription factor binding.
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DOI:
10.1186/s12859-014-0446-3
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发表时间:
2015-01-31
期刊:
影响因子:
3
通讯作者:
Dresch JM
Dresch JM
中科院分区:
生物学4区
文献类型:
--
作者:
Zellers RG;Drewell RA;Dresch JM

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理解控制基因调控的分子机制的一个关键挑战是转录因子蛋白与特定DNA序列结合的特异性的表征。已经开发了许多计算方法来研究这些相互作用,包括简单的单核苷酸和二核苷酸位置权重矩阵模型。在这里,我们开发了一种新的,无偏的计算算法,MARZ,系统地分析所有可能的缺口矩阵在一个固定数量的核苷酸。此外,为了评估这些矩阵模型预测体内结合位点的能力,我们利用一种新的评分系统,并结合已建立的评分方法和统计分析,测试了32种不同的缺口矩阵的性能,以及在果蝇中的HUNCHBACK转录因子。我们的研究结果表明,在许多情况下,缺口矩阵模型可以优于传统的模型,但在分析中考虑的结合位点的相对强度可以深刻地影响特定模型的预测能力。本文的在线版本(doi:10.1186/s12859-014-0446-3)包含补充材料,可供授权用户使用。
A key challenge in understanding the molecular mechanisms that control gene regulation is the characterization of the specificity with which transcription factor proteins bind to specific DNA sequences. A number of computational approaches have been developed to examine these interactions, including simple mononucleotide and dinucleotide position weight matrix models. Here we develop a novel, unbiased computational algorithm, MARZ, that systematically analyzes all possible gapped matrices across a fixed number of nucleotides. In addition, to evaluate the ability of these matrix models to predict in vivo binding sites, we utilize a new scoring system and, in combination with established scoring methods and statistical analysis, test the performance of 32 different gapped matrices on the well characterized HUNCHBACK transcription factor in Drosophila. Our results indicate that in many cases gapped matrix models can outperform traditional models, but that the relative strength of the binding sites considered in the analysis can profoundly influence the predictive ability of specific models. The online version of this article (doi:10.1186/s12859-014-0446-3) contains supplementary material, which is available to authorized users.
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