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NcDNAlign: plausible multiple alignments of non-protein-coding genomic sequences.

机译:NcDNAlign:非蛋白质编码基因组序列的合理的多重比对。

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摘要

Genome-wide multiple sequence alignments (MSAs) are a necessary prerequisite for an increasingly diverse collection of comparative genomic approaches. Here we present a versatile method that generates high-quality MSAs for non-protein-coding sequences. The NcDNAlign pipeline combines pairwise BLAST alignments to create initial MSAs, which are then locally improved and trimmed. The program is optimized for speed and hence is particulary well-suited to pilot studies. We demonstrate the practical use of NcDNAlign in three case studies: the search for ncRNAs in gammaproteobacteria and the analysis of conserved noncoding DNA in nematodes and teleost fish, in the latter case focusing on the fate of duplicated ultra-conserved regions. Compared to the currently widely used genome-wide alignment program TBA, our program results in a 20- to 30-fold reduction of CPU time necessary to generate gammaproteobacterial alignments. A showcase application of bacterial ncRNA prediction based on alignments of both algorithms results in similar sensitivity, false discovery rates, and up to 100 putatively novel ncRNA structures. Similar findings hold for our application of NcDNAlign to the identification of ultra-conserved regions in nematodes and teleosts. Both approaches yield conserved sequences of unknown function, result in novel evolutionary insights into conservation patterns among these genomes, and manifest the benefits of an efficient and reliable genome-wide alignment package. The software is available under the GNU Public License at http://www.bioinf.uni-leipzig.de/Software/NcDNAlign/.
机译:全基因组多重序列比对(MSA)是越来越多的比较基因组方法集合的必要先决条件。在这里,我们提出了一种通用的方法,可以为非蛋白质编码序列生成高质量的MSA。 NcDNAlign管线结合了成对的BLAST比对以创建初始MSA,然后对其进行局部改良和修剪。该程序针对速度进行了优化,因此特别适合于试点研究。我们在三个案例研究中证明了NcDNAlign的实际用途:在γ-变形杆菌中搜索ncRNA,以及在线虫和硬骨鱼中保守非编码DNA的分析,在后一种情况下,重点研究重复的超保守区域的命运。与当前广泛使用的全基因组比对程序TBA相比,我们的程序可将产生γ-变形细菌比对所需的CPU时间减少20至30倍。一个基于两种算法比对的细菌ncRNA预测的展示应用可产生相似的灵敏度,错误发现率以及多达100个推定的新颖ncRNA结构。类似的发现也适用于我们将NcDNAlign用于线虫和硬骨鱼超保守区的鉴定。两种方法都产生功能未知的保守序列,对这些基因组之间的保守模式产生了新的进化见解,并证明了高效,可靠的全基因组比对软件包的好处。该软件可通过GNU公共许可证获得,网址为http://www.bioinf.uni-leipzig.de/Software/NcDNAlign/。

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