OLego: fast and sensitive mapping of spliced mRNA-Seq reads using small seeds.
OLego: fast and sensitive mapping of spliced mRNA-Seq reads using small seeds.
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DOI：
10.1093/nar/gkt216
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发表时间：
2013-05-01
影响因子：
14.9
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Wu J;Anczuków O;Krainer AR;Zhang MQ;Zhang C
分析mRNA-Seq数据的关键步骤是准确有效地将数亿个读段映射到参考基因组和外显子连接点。在这里，我们提出了OLego，一种专门设计用于剪接mRNA-Seq读段的从头定位的算法。OLego采用多种子和扩展方案，不依赖于单独的外部对准器。它通过使用小种子（哺乳动物基因组为14 nt）的策略搜索实现了高灵敏度的连接检测。为了提高准确性并解决连接处的模糊映射，OLego使用内置的统计模型通过剪接位点强度和内含子大小对外显子连接进行评分。在算法的多个步骤中使用Burrows-Wheeler变换来有效地映射种子、定位连接和识别小外显子。OLego是用C++实现的，具有完全的多线程执行，允许快速处理大规模数据。我们系统地评估了OLego的性能与已发表的工具相比，使用模拟和真实的数据。OLego表现出更好的灵敏度，更高或相当的准确性和大大提高的速度。OLego还在小鼠转录组中鉴定了数百个新的微外显子（<30 nt），其中许多是非遗传保守的，可以在体内实验验证。OLego可在http://zhanglab.c2b2.columbia.edu/index.php/OLego上免费获得。
A crucial step in analyzing mRNA-Seq data is to accurately and efficiently map hundreds of millions of reads to the reference genome and exon junctions. Here we present OLego, an algorithm specifically designed for de novo mapping of spliced mRNA-Seq reads. OLego adopts a multiple-seed-and-extend scheme, and does not rely on a separate external aligner. It achieves high sensitivity of junction detection by strategic searches with small seeds (∼14 nt for mammalian genomes). To improve accuracy and resolve ambiguous mapping at junctions, OLego uses a built-in statistical model to score exon junctions by splice-site strength and intron size. Burrows–Wheeler transform is used in multiple steps of the algorithm to efficiently map seeds, locate junctions and identify small exons. OLego is implemented in C++ with fully multithreaded execution, and allows fast processing of large-scale data. We systematically evaluated the performance of OLego in comparison with published tools using both simulated and real data. OLego demonstrated better sensitivity, higher or comparable accuracy and substantially improved speed. OLego also identified hundreds of novel micro-exons (<30 nt) in the mouse transcriptome, many of which are phylogenetically conserved and can be validated experimentally in vivo. OLego is freely available at http://zhanglab.c2b2.columbia.edu/index.php/OLego.
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