An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance
An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance
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DOI：
10.1186/1471-2105-9-89
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发表时间：
2008-02-07
影响因子：
3
通讯作者：
Oliveira, Arlindo L.
中科院分区：
文献类型：
--
作者：
Casimiro, Ana C.;Vinga, Susana;Oliveira, Arlindo L.
背景：Motif查找算法已经发展到能够使用高效的计算方法来检测生物序列中的模式。然而，输出的后验分类仍然存在一定的局限性，这使得很难评估所发现的基序的生物学意义。先前的工作强调了DNA序列中基序位置偏差的存在，这可能不仅表明该模式很重要，而且还提供了这些模式优先发生的位置的提示。结果：我们提出将位置均匀性检验和过度代表性检验相结合，以提高图案分类的准确性。利用人工数据，我们比较了三种不同的统计检验（卡方检验、柯尔莫戈洛夫-斯米尔诺夫检验和卡方自举法），以评估给定基序是否均匀地出现在基因的启动子区域。使用在该数据集中表现较好的测试，我们继续研究了几种已知的顺式调控元件在不同生物（S. cerevisiae， H. sapiens， D. melanogaster， E. coli和几种双子叶植物）启动子序列中的位置分布。结果表明，位置守恒与转录机制有关。结论：我们得出结论，许多生物学相关的基序在基因的启动子区域出现异质性分布，因此，非均匀性是生物学相关性的一个很好的指标，可以用来补充常用的过度代表性测试。在这篇文章中，我们提出了对S. cerevisiae数据集获得的结果。
Background: Motif finding algorithms have developed in their ability to use computationally efficient methods to detect patterns in biological sequences. However the posterior classification of the output still suffers from some limitations, which makes it difficult to assess the biological significance of the motifs found. Previous work has highlighted the existence of positional bias of motifs in the DNA sequences, which might indicate not only that the pattern is important, but also provide hints of the positions where these patterns occur preferentially.Results: We propose to integrate position uniformity tests and over-representation tests to improve the accuracy of the classification of motifs. Using artificial data, we have compared three different statistical tests ( Chi- Square, Kolmogorov- Smirnov and a Chi- Square bootstrap) to assess whether a given motif occurs uniformly in the promoter region of a gene. Using the test that performed better in this dataset, we proceeded to study the positional distribution of several well known cis- regulatory elements, in the promoter sequences of different organisms ( S. cerevisiae, H. sapiens, D. melanogaster, E. coli and several Dicotyledons plants). The results show that position conservation is relevant for the transcriptional machinery.Conclusion: We conclude that many biologically relevant motifs appear heterogeneously distributed in the promoter region of genes, and therefore, that non- uniformity is a good indicator of biological relevance and can be used to complement over- representation tests commonly used. In this article we present the results obtained for the S. cerevisiae data sets.