Fast and sensitive multiple alignment of large genomic sequences -: art. no. 66
Fast and sensitive multiple alignment of large genomic sequences -: art. no. 66
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DOI：
10.1186/1471-2105-4-66
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发表时间：
2003-12-23
影响因子：
3
通讯作者：
Morgenstern, B
中科院分区：
文献类型：
--
作者：
Brudno, M;Chapman, M;Morgenstern, B
背景：基因组序列比对是基因组分析和注释的一种强大方法，因为比对通常用于识别功能位点，如基因或调控元件。随着部分或完全测序基因组数量的增加，多重比对在这些研究中发挥着越来越重要的作用。近年来，各种工具成对和多基因组比对已被提出。其中一些速度非常快，但通常以牺牲灵敏度为代价来获得效率。结合速度和灵敏度的一种方法是使用锚定对准方法。在第一步中，快速搜索程序识别强局部序列相似性链。在第二步中，使用一种较慢但更精确的方法对齐这些锚点之间的区域。结果：本文提出了一种新的混沌算法，用于快速识别局部成对序列相似性链。利用CHAOS计算的局部对准作为锚点，提高了DIALIGN（一种速度慢但灵敏度高的多对准工具）的运行时间。我们证明，通过这种方式，DIALIGN的运行时间可以减少95%以上的bac大小和更长的序列，而不影响结果比对的质量。我们将我们的方法应用于干细胞白血病（SCL）基因周围的一组五个基因组序列，并证明外显子和小调控元件可以通过我们的多重比对程序识别。结论：新型CHAOS局部对准工具是在不降低对准质量的前提下显著加快DIALIGN等全局对准工具速度的有效方法。我们同样证明了DIALIGN/CHAOS组合能够准确地对齐远同源物中的短调控序列。
Background: Genomic sequence alignment is a powerful method for genome analysis and annotation, as alignments are routinely used to identify functional sites such as genes or regulatory elements. With a growing number of partially or completely sequenced genomes, multiple alignment is playing an increasingly important role in these studies. In recent years, various tools for pair-wise and multiple genomic alignment have been proposed. Some of them are extremely fast, but often efficiency is achieved at the expense of sensitivity. One way of combining speed and sensitivity is to use an anchored-alignment approach. In a first step, a fast search program identifies a chain of strong local sequence similarities. In a second step, regions between these anchor points are aligned using a slower but more accurate method.Results: Herein, we present CHAOS, a novel algorithm for rapid identification of chains of local pair-wise sequence similarities. Local alignments calculated by CHAOS are used as anchor points to improve the running time of DIALIGN, a slow but sensitive multiple-alignment tool. We show that this way, the running time of DIALIGN can be reduced by more than 95% for BAC-sized and longer sequences, without affecting the quality of the resulting alignments. We apply our approach to a set of five genomic sequences around the stem-cell-leukemia (SCL) gene and demonstrate that exons and small regulatory elements can be identified by our multiple-alignment procedure.Conclusion: We conclude that the novel CHAOS local alignment tool is an effective way to significantly speed up global alignment tools such as DIALIGN without reducing the alignment quality. We likewise demonstrate that the DIALIGN/CHAOS combination is able to accurately align short regulatory sequences in distant orthologues.