Stochastic sampling of the RNA structural alignment space.

Stochastic sampling of the RNA structural alignment space.
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DOI:
10.1093/nar/gkp276
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发表时间:
2009-07
影响因子:
14.9
通讯作者:
Mathews DH
Mathews DH
中科院分区:
生物学2区
文献类型:
--
作者:
Harmanci AO;Sharma G;Mathews DH

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提出了一种通过对两个同源RNA序列的“结构比对”空间(即它们的比对和共同二级结构的联合空间)采样来预测其共同二级结构和排列的新方法。根据基于伪自由能量变化的伪玻尔兹曼分布对结构对准空间进行采样,该分布结合了热力学模型的碱基配对概率和隐马尔可夫模型的对准概率。通过对两个序列的隐式比较分析,该方法对玻尔兹曼集合的单序列采样进行了改进。聚类分析表明,与单序列法相比,联合采样法得到的样本聚类更紧密。平均而言,联合采样生成的结构和排列样本中,人口最多的集群的代表性(质心)结构和排列分别比单序列采样和单独基于序列的排列更准确。平均而言,在所有质心中最接近已知结构的“最佳”质心结构比其他方法的结构预测更准确。此外,聚类分析平均确定了一些聚类,其质心可以作为备选的候选。建议的方法的源代码可以从http://rna.urmc.rochester.edu下载。
A novel method is presented for predicting the common secondary structures and alignment of two homologous RNA sequences by sampling the ‘structural alignment’ space, i.e. the joint space of their alignments and common secondary structures. The structural alignment space is sampled according to a pseudo-Boltzmann distribution based on a pseudo-free energy change that combines base pairing probabilities from a thermodynamic model and alignment probabilities from a hidden Markov model. By virtue of the implicit comparative analysis between the two sequences, the method offers an improvement over single sequence sampling of the Boltzmann ensemble. A cluster analysis shows that the samples obtained from joint sampling of the structural alignment space cluster more closely than samples generated by the single sequence method. On average, the representative (centroid) structure and alignment of the most populated cluster in the sample of structures and alignments generated by joint sampling are more accurate than single sequence sampling and alignment based on sequence alone, respectively. The ‘best’ centroid structure that is closest to the known structure among all the centroids is, on average, more accurate than structure predictions of other methods. Additionally, cluster analysis identifies, on average, a few clusters, whose centroids can be presented as alternative candidates. The source code for the proposed method can be downloaded at http://rna.urmc.rochester.edu.
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影响因子: 3
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