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A local multiple alignment method for detection of non-coding RNA sequences

机译:用于检测非编码RNA序列的局部多重比对方法

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摘要

MOTIVATION: Non-coding RNAs (ncRNAs) show a unique evolutionary process in which the substitutions of distant bases are correlated in order to conserve the secondary structure of the ncRNA molecule. Therefore, the multiple alignment method for the detection of ncRNAs should take into account both the primary sequence and the secondary structure. Recently, there has been intense focus on multiple alignment investigations for the detection of ncRNAs; however, most of the proposed methods are designed for global multiple alignments. For this reason, these methods are not appropriate to identify locally conserved ncRNAs among genomic sequences. A more efficient local multiple alignment method for the detection of ncRNAs is required. RESULTS: We propose a new local multiple alignment method for the detection of ncRNAs. This method uses a local multiple alignment construction procedure inspired by ProDA, which is a local multiple aligner program for protein sequences with repeated and shuffled elements. To align sequences based on secondary structure information, we propose a new alignment model which incorporates secondary structure features. We define the conditional probability of an alignment via a conditional random field and use a gamma-centroid estimator to align sequences. The locally aligned subsequences are clustered into blocks of approximately globally alignable subsequences between pairwise alignments. Finally, these blocks are multiply aligned via MXSCARNA. In benchmark experiments, we demonstrate the high ability of the implemented software, SCARNA_LM, for local multiple alignment for the detection of ncRNAs. AVAILABILITY: The C++ source code for SCARNA_LM and its experimental datasets are available at http://www.ncrna.org/software/scarna_lm/download. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
机译:动机:非编码RNA(ncRNA)显示出独特的进化过程,其中远距离碱基的取代相互关联,以保存ncRNA分子的二级结构。因此,用于检测ncRNA的多重比对方法应同时考虑一级序列和二级结构。最近,人们非常关注用于ncRNA检测的多重比对研究。但是,大多数建议的方法都是针对全局多重比对设计的。因此,这些方法不适用于在基因组序列之间鉴定本地保守的ncRNA。需要一种更有效的局部多重比对方法来检测ncRNA。结果:我们提出了一种新的本地多重比对方法来检测ncRNA。该方法使用受ProDA启发的局部多重比对构建程序,ProDA是针对具有重复和改组元素的蛋白质序列的局部多重比对程序。为了根据二级结构信息比对序列,我们提出了一个新的比对模型,其中包含二级结构特征。我们通过条件随机字段定义比对的条件概率,并使用伽玛质心估计器来比对序列。局部比对的子序列聚类为成对的比对之间的近似全局可比的子序列的块。最后,这些模块通过MXSCARNA进行多重比对。在基准实验中,我们证明了已实现的软件SCARNA_LM对于检测ncRNA的局部多重比对具有很高的能力。可用性:SCARNA_LM的C ++源代码及其实验数据集可从http://www.ncrna.org/software/scarna_lm/download获得。补充信息:补充数据可从Bioinformatics在线获得。

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