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首页> 外文期刊>Computational Biology and Bioinformatics, IEEE/ACM Transactions on >A Novel Heuristic for Local Multiple Alignment of Interspersed DNA Repeats
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A Novel Heuristic for Local Multiple Alignment of Interspersed DNA Repeats

机译：散布的DNA重复的局部多重比对的新型启发式。

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摘要

Pairwise local sequence alignment methods have been the prevailing technique to identify homologous nucleotides between related species. However, existing methods that identify and align all homologous nucleotides in one or more genomes have suffered from poor scalability and limited accuracy. We propose a novel method that couples a gapped extension heuristic with an efficient filtration method for identifying interspersed repeats in genome sequences. During gapped extension, we use the MUSCLE implementation of progressive global multiple alignment with iterative refinement. The resulting gapped extensions potentially contain alignments of unrelated sequence. We detect and remove such undesirable alignments using a hidden Markov model (HMM) to predict the posterior probability of homology. The HMM emission frequencies for nucleotide substitutions can be derived from any time-reversible nucleotide substitution matrix. We evaluate the performance of our method and previous approaches on a hybrid data set of real genomic DNA with simulated interspersed repeats. Our method outperforms a related method in terms of sensitivity, positive predictive value, and localizing boundaries of homology. The described methods have been implemented in freely available software, Repeatoire, available from: http://wwwabi.snv.jussieu.fr/public/Repeatoire.
机译：成对的局部序列比对方法已经成为识别相关物种之间同源核苷酸的流行技术。然而，在一个或多个基因组中鉴定和比对所有同源核苷酸的现有方法遭受了差的可扩展性和有限的准确性。我们提出了一种新颖的方法，将空缺的扩展启发式方法与有效的过滤方法相结合，用于识别基因组序列中的散布重复。在有间隔的扩展过程中，我们使用带有迭代细化的渐进全局多重对齐的MUSCLE实现。产生的空位延伸可能包含不相关序列的比对。我们使用隐马尔可夫模型（HMM）来检测并删除此类不良对齐方式，以预测同源性的后验概率。核苷酸取代的HMM发射频率可以从任何时间可逆的核苷酸取代矩阵中得出。我们在模拟散布的重复序列的真实基因组DNA混合数据集上评估我们的方法和先前方法的性能。我们的方法在敏感性，阳性预测值和同源性局部边界方面均优于相关方法。所描述的方法已经在可免费获得的软件Repeatoire中实现，该软件可从以下网站获得：http：//wwwabi.snv.jussieu.fr/public/Repeatoire。

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