The value of position-specific priors in motif discovery using MEME.

The value of position-specific priors in motif discovery using MEME.
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DOI:
10.1186/1471-2105-11-179
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发表时间:
2010-04-09
期刊:
影响因子:
3
通讯作者:
Machanick P
Machanick P
中科院分区:
生物学4区
文献类型:
--
作者:
Bailey TL;Bodén M;Whitington T;Machanick P

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位置特定的先验已被证明是一种灵活和优雅的方式来扩展基于Gibbs采样器的基序发现算法的能力。许多类型的信息,包括序列保守性,核小体定位,和负的例子,可以转换成一个先验的基序位点的位置,然后指导序列基序发现算法。这种方法已被证明赋予许多基于吉布斯采样器的基序发现方法的保护和歧视性基序发现方法的好处,但以前没有研究过基于期望最大化(EM)的方法。我们扩展了流行的EM为基础的MEME算法,利用特定位置的先验知识,并证明其有效性发现转录因子(TF)基序在酵母和小鼠的DNA序列。利用一个有区别的,基于保守性的先验知识,大大提高了MEME在156个酵母TF ChIP芯片数据集中发现基序的能力,使其找到正确基序的数据集数量增加了一倍多。在这些数据集上,使用先验知识的MEME比其他八种基于保护的基序发现方法具有更高的成功率。我们还表明,相同类型的先验提高了MEME在小鼠TF ChIP-seq数据中发现的基序的准确性,并且这些基序往往具有使用相同先验的Gibbs采样算法发现的略高质量。我们的结论是,使用特定位置的先验知识可以大大提高基于EM的基序发现算法,如MEME算法的功率。
Position-specific priors have been shown to be a flexible and elegant way to extend the power of Gibbs sampler-based motif discovery algorithms. Information of many types–including sequence conservation, nucleosome positioning, and negative examples–can be converted into a prior over the location of motif sites, which then guides the sequence motif discovery algorithm. This approach has been shown to confer many of the benefits of conservation-based and discriminative motif discovery approaches on Gibbs sampler-based motif discovery methods, but has not previously been studied with methods based on expectation maximization (EM). We extend the popular EM-based MEME algorithm to utilize position-specific priors and demonstrate their effectiveness for discovering transcription factor (TF) motifs in yeast and mouse DNA sequences. Utilizing a discriminative, conservation-based prior dramatically improves MEME's ability to discover motifs in 156 yeast TF ChIP-chip datasets, more than doubling the number of datasets where it finds the correct motif. On these datasets, MEME using the prior has a higher success rate than eight other conservation-based motif discovery approaches. We also show that the same type of prior improves the accuracy of motifs discovered by MEME in mouse TF ChIP-seq data, and that the motifs tend to be of slightly higher quality those found by a Gibbs sampling algorithm using the same prior. We conclude that using position-specific priors can substantially increase the power of EM-based motif discovery algorithms such as MEME algorithm.
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