DIALIGN-T: An improved algorithm for segment-based multiple sequence alignment

DIALIGN-T: An improved algorithm for segment-based multiple sequence alignment
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DOI:
10.1186/1471-2105-6-66
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发表时间:
2005-03-22
期刊:
影响因子:
3
通讯作者:
Morgenstern, B
Morgenstern, B
中科院分区:
生物学4区
文献类型:
--
作者:
Subramanian, AR;Weyer-Menkhoff, J;Morgenstern, B

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背景资料:我们提出了一个完整的重新实现的基于片段的方法,多蛋白质比对,包含了一些改进相比,以前的版本2.2的DIALIGN。这个先前的版本是上级的Needleman-Wunsch为基础的多比对程序的局部相关的序列集。然而,它往往优于这些方法的数据集与全球性的,但弱相似性在primary-sequence level.Results:在本文中,我们讨论的DIALIGN的优势和劣势,鉴于基本的目标函数。基于这些结果,我们提出了几个算法来改进基于段的对齐方法。对于成对比对,我们实现了一个片段链算法,有利于链的低得分本地比对孤立的高得分片段。对于多重比对,我们使用了一种改进的贪婪程序,它对虚假的局部序列相似性不太敏感。为了评估我们在全球相关蛋白质家族上的方法,我们使用了著名的数据库BAliBASE。对于局部相关序列的基准测试,我们创建了一个新的参考数据库,称为IRMBASE,其中包括模拟保守基序植入到非相关的随机sequence.Conclusion:在BAliBASE上,我们的新程序的性能显着优于以前版本的DIALIGN和媲美标准的全球比对器CLUSTAL W,虽然它是优于一些新开发的程序,专注于全球比对。在IRMBASE中的本地相关测试集上,我们的方法优于我们评估的所有其他程序。
Background: We present a complete re-implementation of the segment-based approach to multiple protein alignment that contains a number of improvements compared to the previous version 2.2 of DIALIGN. This previous version is superior to Needleman-Wunsch-based multi-alignment programs on locally related sequence sets. However, it is often outperformed by these methods on data sets with global but weak similarity at the primary-sequence level.Results: In the present paper, we discuss strengths and weaknesses of DIALIGN in view of the underlying objective function. Based on these results, we propose several heuristics to improve the segment-based alignment approach. For pairwise alignment, we implemented a fragment-chaining algorithm that favours chains of low-scoring local alignments over isolated high-scoring fragments. For multiple alignment, we use an improved greedy procedure that is less sensitive to spurious local sequence similarities. To evaluate our method on globally related protein families, we used the well-known database BAliBASE. For benchmarking tests on locally related sequences, we created a new reference database called IRMBASE which consists of simulated conserved motifs implanted into non-related random sequences.Conclusion: On BAliBASE, our new program performs significantly better than the previous version of DIALIGN and is comparable to the standard global aligner CLUSTAL W, though it is outperformed by some newly developed programs that focus on global alignment. On the locally related test sets in IRMBASE, our method outperforms all other programs that we evaluated.