Indel seeds for homology search
Indel seeds for homology search
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DOI：
10.1093/bioinformatics/btl263
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发表时间：
2006-07-01
期刊：
影响因子：
5.8
通讯作者：
Benson, Gary
中科院分区：
文献类型：
--
作者：
Mak, Denise;Gelfand, Yevgeniy;Benson, Gary
我们感兴趣的是检测同源基因组DNA序列，目的是定位近似的反向、散布和串联重复序列。标准搜索技术首先检测查询序列和数据库序列之间的称为种子的小匹配部分。连续种子模型已经存在很多年了。最近，在不增加随机命中率的情况下，间隔种子被证明比连续种子更敏感。为了确定一种种子模型相对于另一种种子模型的优越性，必须选择一种同源序列比对模型。以前评估间隔和连续种子的研究假设在这些比对中发生匹配和不匹配，而不是插入和缺失(Indels)。当搜索蛋白质编码序列(人类基因组的5%)时，这可能是合适的，但当在大多数基因组序列中寻找INDELs常见的重复序列时，这是不合适的。在本文中，我们假设了一个包含Indels的同源序列比对模型，并描述了一个新的种子模型，称为Indel Seed，它显式地允许Indels。我们给出了一个计算Indel种子敏感度的等待时间公式，并表明当同源包含Indels时，Indel种子的性能明显优于连续的和间隔的种子。我们讨论了使用Indel种子的实际方面，最后我们展示了使用Indel种子和间隔种子在狗基因组中搜索反向重复的结果。
We are interested in detecting homologous genomic DNA sequences with the goal of locating approximate inverted, interspersed, and tandem repeats. Standard search techniques start by detecting small matching parts, called seeds, between a query sequence and database sequences. Contiguous seed models have existed for many years. Recently, spaced seeds were shown to be more sensitive than contiguous seeds without increasing the random hit rate. To determine the superiority of one seed model over another, a model of homologous sequence alignment must be chosen. Previous studies evaluating spaced and contiguous seeds have assumed that matches and mismatches occur within these alignments, but not insertions and deletions (indels). This is perhaps appropriate when searching for protein coding sequences (< 5% of the human genome), but is inappropriate when looking for repeats in the majority of genomic sequence where indels are common. In this paper, we assume a model of homologous sequence alignment which includes indels and we describe a new seed model, called indel seeds, which explicitly allows indels. We present a waiting time formula for computing the sensitivity of an indel seed and show that indel seeds significantly outperform contiguous and spaced seeds when homologies include indels. We discuss the practical aspect of using indel seeds and finally we present results from a search for inverted repeats in the dog genome using both indel and spaced seeds.