Multi-CAR: a tool of contig scaffolding using multiple references.

Multi-CAR: a tool of contig scaffolding using multiple references.
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多车:使用多个参考的重叠式脚手架工具。

DOI:
10.1186/s12859-016-1328-7
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发表时间:
2016-12-23
期刊:
影响因子:
3
通讯作者:
Lu CL
Lu CL
中科院分区:
生物学4区
文献类型:
--
作者:
Chen KT;Chen CJ;Shen HT;Liu CL;Huang SH;Lu CL

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通过当前的下一代测序技术从短读段组装的基因组草案只是重叠群的集合,其沿着被测序的基因组的相对位置和方向是未知的。为了进一步获得其完整序列,通常应用重叠群支架过程来对基因组草案中的重叠群进行排序和定向。尽管已经提出了几种基于参考的支架工具,但如果目标基因组和参考基因组之间存在重排或者它们的系统发育关系遥远,它们可能会产生错误的支架。这可能表明单个参考基因组可能不足以产生基因组草案的正确支架。在这项研究中,我们设计了一种简单的启发式方法,将我们的单一基于参考的支架工具 CAR 进一步修改为一种名为 Multi-CAR 的新工具,这样它就可以利用相关生物体的多个完整基因组作为参考,以更准确地对基因组草案的重叠群进行排序和定向。在实际使用中,我们的 Multi-CAR 不需要有关草图和参考基因组以及双端读​​取文库之间的系统发育关系的先验知识。为了验证 Multi-CAR,我们在由多个原核基因组组成的真实数据集上对其进行了测试,并将其准确性性能与其他基于多个参考的支架工具 Ragout 和 MeDuSa 进行了比较。我们的实验结果最终表明,Multi-CAR 在灵敏度、精确度、基因组覆盖度、支架数量和支架 N50 大小方面确实优于 Ragout 和 MeDuSa。 Multi-CAR 是一种有效的工具,可以根据多个参考基因组更准确地对基因组草案的重叠群进行排序和定向。 Multi-CAR 的网络服务器可免费使用:http://genome.cs.nthu.edu.tw/Multi-CAR/。
A draft genome assembled by current next-generation sequencing techniques from short reads is just a collection of contigs, whose relative positions and orientations along the genome being sequenced are unknown. To further obtain its complete sequence, a contig scaffolding process is usually applied to order and orient the contigs in the draft genome. Although several single reference-based scaffolding tools have been proposed, they may produce erroneous scaffolds if there are rearrangements between the target and reference genomes or their phylogenetic relationship is distant. This may suggest that a single reference genome may not be sufficient to produce correct scaffolds of a draft genome. In this study, we design a simple heuristic method to further revise our single reference-based scaffolding tool CAR into a new one called Multi-CAR such that it can utilize multiple complete genomes of related organisms as references to more accurately order and orient the contigs of a draft genome. In practical usage, our Multi-CAR does not require prior knowledge concerning phylogenetic relationships among the draft and reference genomes and libraries of paired-end reads. To validate Multi-CAR, we have tested it on a real dataset composed of several prokaryotic genomes and also compared its accuracy performance with other multiple reference-based scaffolding tools Ragout and MeDuSa. Our experimental results have finally shown that Multi-CAR indeed outperforms Ragout and MeDuSa in terms of sensitivity, precision, genome coverage, scaffold number and scaffold N50 size. Multi-CAR serves as an efficient tool that can more accurately order and orient the contigs of a draft genome based on multiple reference genomes. The web server of Multi-CAR is freely available at http://genome.cs.nthu.edu.tw/Multi-CAR/.