在短序列中快速发现motif

Honglei Liu, Fangqiu Han, Hongjun Zhou, Xifeng Yan, K. Kosik
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引用次数: 16

摘要

序列数据中的基序发现是许多生物学问题的基础,如抗体生物标志物鉴定。仪器技术的最新进展使一次生成数千个蛋白质序列成为可能,这为现有的基序查找算法提出了一个大数据问题:它们要么只能在几百个序列的小范围内工作,要么必须以准确性为代价提高效率。在这项工作中,我们证明了通过智能聚类序列,可以显着提高所有现有基序查找算法的可扩展性,而不会失去准确性。为此,提出了一种基于锚点的序列聚类算法(ASC),将序列数据集划分为多个较小的聚类,从而将具有相同基序的序列定位到同一聚类中。然后将现有的基序查找算法应用于每个单独的聚类来生成基序。最后,将多个集群的结果合并在一起作为最终输出。实验结果表明,我们的方法是通用的,并且比传统的motif查找算法快了几个数量级。它可以在现有算法无法处理的范围内从蛋白质序列中发现基序。特别是,ASC将非常流行的motif查找算法MEME的运行时间从几周缩短到几分钟,并且精度更高。
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Fast motif discovery in short sequences
Motif discovery in sequence data is fundamental to many biological problems such as antibody biomarker identification. Recent advances in instrumental techniques make it possible to generate thousands of protein sequences at once, which raises a big data issue for the existing motif finding algorithms: They either work only in a small scale of several hundred sequences or have to trade accuracy for efficiency. In this work, we demonstrate that by intelligently clustering sequences, it is possible to significantly improve the scalability of all the existing motif finding algorithms without losing accuracy at all. An anchor based sequence clustering algorithm (ASC) is thus proposed to divide a sequence dataset into multiple smaller clusters so that sequences sharing the same motif will be located into the same cluster. Then an existing motif finding algorithm can be applied to each individual cluster to generate motifs. In the end, the results from multiple clusters are merged together as final output. Experimental results show that our approach is generic and orders of magnitude faster than traditional motif finding algorithms. It can discover motifs from protein sequences in the scale that no existing algorithm can handle. In particular, ASC reduces the running time of a very popular motif finding algorithm, MEME, from weeks to a few minutes with even better accuracy.
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