Finding regulatory DNA motifs using alignment-free evolutionary conservation information.
Finding regulatory DNA motifs using alignment-free evolutionary conservation information.
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DOI：
10.1093/nar/gkp1166
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发表时间：
2010-04
影响因子：
14.9
通讯作者：
Hartemink AJ
中科院分区：
文献类型：
--
作者：
Gordân R;Narlikar L;Hartemink AJ
随着越来越多的真核生物基因组被测序，旨在检测基因间序列中调控元件的比较研究变得越来越普遍。用于转录因子（TF）结合位点发现的大多数比较方法利用正向调节区的全局或局部比对来评估特定DNA位点是否在相关生物体中保守，从而更可能是功能性的。由于结合位点通常很短，有时是简并的，并且通常与方向无关，因此比对算法可能无法正确地将它们对齐。在这里，我们提出了一种新的，无干扰的方法，使用TF结合位点发现的保守信息。我们放宽了保守位点的定义：我们认为一个调控区内的DNA位点在一个正向序列中是保守的，如果它出现在该序列的任何地方，无论方向如何。我们使用这个定义来获得信息先验的DNA序列的位置，并将这些先验到吉布斯采样算法的基序发现。我们的方法简单而快速。它既不需要序列比对，也不需要同源序列之间的系统发育关系，但它比其他方法更有效地处理真实的生物数据。
As an increasing number of eukaryotic genomes are being sequenced, comparative studies aimed at detecting regulatory elements in intergenic sequences are becoming more prevalent. Most comparative methods for transcription factor (TF) binding site discovery make use of global or local alignments of orthologous regulatory regions to assess whether a particular DNA site is conserved across related organisms, and thus more likely to be functional. Since binding sites are usually short, sometimes degenerate, and often independent of orientation, alignment algorithms may not align them correctly. Here, we present a novel, alignment-free approach for using conservation information for TF binding site discovery. We relax the definition of conserved sites: we consider a DNA site within a regulatory region to be conserved in an orthologous sequence if it occurs anywhere in that sequence, irrespective of orientation. We use this definition to derive informative priors over DNA sequence positions, and incorporate these priors into a Gibbs sampling algorithm for motif discovery. Our approach is simple and fast. It requires neither sequence alignments nor the phylogenetic relationships between the orthologous sequences, yet it is more effective on real biological data than methods that do.
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