A Gibbs sampler for identification of symmetrically structured, spaced DNA motifs with improved estimation of the signal length
A Gibbs sampler for identification of symmetrically structured, spaced DNA motifs with improved estimation of the signal length
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DOI：
10.1093/bioinformatics/bti336
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发表时间：
2005-05-15
期刊：
影响因子：
5.8
通讯作者：
Makeev, VJ
中科院分区：
文献类型：
--
作者：
Favorov, AV;Gelfand, MS;Makeev, VJ
动机：转录调控蛋白因子常常作为同二聚体或异二聚体结合DNA。因此，它们识别的是反向、正向重复或间隔的基序对形式的结构化DNA基序。然而，由于这些基序高度分化，它们往往难以识别。将基序结构明确纳入基序识别算法可提高对高度分化基序的识别效率以及对基序几何参数的估计。
结果：我们对吉布斯采样基序提取算法（SeSiMCMC，基于马尔可夫链蒙特卡罗的序列相似性）进行了改进，该算法可在一组未比对的DNA序列中找到这些类型的结构化基序以及非结构化基序。它采用了改进的基序和间隔长度估计量。以严格的贝叶斯方式考虑了一个序列不包含任何基序的概率。我们已将该算法应用于来自两个参与呼吸作用的大肠杆菌调节子的一组基因上游区域。我们已经证明，考虑对称基序结构可使算法更准确地识别弱基序。在所研究的实例中，ArcA结合位点被证明具有正向间隔重复的结构，而NarP结合位点呈现出回文结构。
Motivation: Transcription regulatory protein factors often bind DNA as homo-dimers or hetero-dimers. Thus they recognize structured DNA motifs that are inverted or direct repeats or spaced motif pairs. However, these motifs are often difficult to identify owing to their high divergence. The motif structure included explicitly into the motif recognition algorithm improves recognition efficiency for highly divergent motifs as well as estimation of motif geometric parameters.Result: We present a modification of the Gibbs sampling motif extraction algorithm, SeSiMCMC (Sequence Similarities by Markov Chain Monte Carlo), which finds structured motifs of these types, as well as non-structured motifs, in a set of unaligned DNA sequences. It employs improved estimators of motif and spacer lengths. The probability that a sequence does not contain any motif is accounted for in a rigorous Bayesian manner. We have applied the algorithm to a set of upstream regions of genes from two Escherichia coli regulons involved in respiration. We have demonstrated that accounting for a symmetric motif structure allows the algorithm to identify weak motifs more accurately. In the examples studied, ArcA binding sites were demonstrated to have the structure of a direct spaced repeat, whereas NarP binding sites exhibited the palindromic structure.