progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement.
progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement.
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DOI：
10.1371/journal.pone.0011147
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发表时间：
2010-06-25
期刊：
影响因子：
3.7
通讯作者：
Perna NT
中科院分区：
文献类型：
--
作者：
Darling AE;Mau B;Perna NT
多基因组比对仍然是一个具有挑战性的问题。重组的影响包括重排、片段复制、获得和丢失，甚至在密切相关的生物体中也可以产生同源性的镶嵌模式。我们描述了一种新的方法来对齐两个或多个基因组，这些基因组由于重组和大量的片段增益和损失（通量）而经历了重排。我们证明，新方法可以准确地对齐在一些，但不是所有的基因组，我们以前的工作没有处理的重要情况下保守的区域。该方法使用了一种新的对齐目标得分称为总和对断点得分，这有利于准确检测重排断点时，基因组具有不等的基因内容。我们还应用概率比对过滤方法来去除不相关序列的错误比对，这在其他基因组比对方法中常见。我们描述了用于量化基因组比对准确性的新指标，其测量重排断点预测和插入缺失预测的质量。新的基因组比对算法在基因组经历了生物学上可行的基因组重排、片段获得和丢失的情况下表现出高准确性。我们应用新的算法，从属大肠杆菌，志贺氏菌和沙门氏菌的23个基因组。全基因组多重比对分析使我们能够扩展先前定义的核心和泛基因组的概念，不仅包括注释的基因，而且还包括具有潜在调控作用的非编码区。23种肠杆菌的核心基因组全长为2.46Mbp，泛基因组全长为15.2Mbp。我们记录了大量的人口水平的变化，这些生物体驱动的部分收益和损失。有趣的是，许多变异性在于基因间区域，表明肠杆菌可能表现出监管分歧。我们的软件生成的多基因组比对为比较基因组和群体基因组研究提供了一个平台。实施所述基因组比对方法的免费开源软件可从http://gel.ahabs.wisc.edu/mauve获得。
Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms. We describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux). We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence. The multiple genome alignments generated by our software provide a platform for comparative genomic and population genomic studies. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve.
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