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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >A Fast and Sensitive Algorithm for Aligning ESTs to the Human Genome
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A Fast and Sensitive Algorithm for Aligning ESTs to the Human Genome

机译：将EST与人类基因组比对的快速灵敏算法

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摘要

There is a pressing need to align the growing set of expressed sequence tags (ESTs) with the newly sequenced human genome. However, the problem is complicated by the exon/intron structure of eukaryotic genes, misread nucleotides in ESTs, and the millions of repetitive sequences in genomic sequences. To solve this problem, algorithms that use dynamic programming have been proposed. In reality, however, these algorithms require an enormous amount of processing time. In an effort to improve the computational efficiency of these classical DP algorithms, we developed software that fully utilizes lookup-tables to detect the start- and endpoints of an EST within a given DNA sequence efficiently, and subsequently promptly identify exons and introns. In addition, the locations of all splice sites must be calculated correctly with high sensitivity and accuracy, while retaining high computational efficiency. This goal is hard to accomplish in practice, due to misread nucleotides in ESTs and repetitive sequences in the genome. Nevertheless, we present two heuristics that effectively settle this issue. Experimental results confirm that our technique improves the overall computation time by orders of magnitude compared with common tools, such as SIM4 and BLAT, and simultaneously attains high sensitivity and accuracy against a clean dataset of documented genes.
机译：迫切需要使不断增长的表达序列标签（EST）组与新测序的人类基因组对齐。然而，由于真核基因的外显子/内含子结构，EST中核苷酸的误读以及基因组序列中的数百万个重复序列，使问题变得复杂。为了解决这个问题，已经提出了使用动态编程的算法。然而，实际上，这些算法需要大量的处理时间。为了提高这些经典DP算法的计算效率，我们开发了一种软件，该软件充分利用查找表来有效检测给定DNA序列内EST的起点和终点，并随后迅速识别外显子和内含子。此外，必须在保持高计算效率的同时，以高灵敏度和准确性正确计算所有剪接位点的位置。由于EST中核苷酸的错误读取和基因组中的重复序列，在实践中很难实现该目标。但是，我们提出了两种启发式方法来有效解决此问题。实验结果证实，与SIM4和BLAT等常用工具相比，我们的技术将整体计算时间缩短了几个数量级，并且针对记录的干净基因数据集实现了高灵敏度和准确性。

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