Epigenetic priors for identifying active transcription factor binding sites
Epigenetic priors for identifying active transcription factor binding sites
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DOI：
10.1093/bioinformatics/btr614
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发表时间：
2012-01-01
期刊：
影响因子：
5.8
通讯作者：
Bailey, Timothy L.
中科院分区：
文献类型：
--
作者：
Cuellar-Partida, Gabriel;Buske, Fabian A.;Bailey, Timothy L.
动机准确了解转录因子在特定细胞类型或特定条件下的全基因组结合对于理解转录调控是必要的。通过使用组蛋白修饰和DNase I等表观遗传学数据，可及性数据已被证明改进了基于Motif的预测这种结合的方法，但这种方法尚未被完全开发。结果我们描述了一种将一个或多个表观遗传学数据轨迹与标准DNA序列基序模型相结合的概率方法，以提高我们识别活性转录因子结合位点(TFBs)的能力。我们将每种数据类型转换为位置特定的概率先验，并将这些先验与传统的概率模体模型相结合来计算对数后验概率分数。我们的实验，使用组蛋白修饰H3K4me1，H3K4me3，H3K9ac和H3K27ac，以及DNaseI敏感性，最终表明对数后验优势分数一致地优于基于相同数据的简单二进制过滤器。我们还表明，我们的方法与更复杂的方法蜈蚣相比具有竞争性，并表明对数后验优势计分方法的相对简单使其成为基于DNA和表观遗传学证据识别功能性TFBS的一种有吸引力的和非常通用的方法。
Motivation Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored.Results We describe a probabilistic method for combining one or more tracks of epigenetic data with a standard DNA sequence motif model to improve our ability to identify active transcription factor binding sites (TFBSs). We convert each data type into a position-specific probabilistic prior and combine these priors with a traditional probabilistic motif model to compute a log-posterior odds score. Our experiments, using histone modifications H3K4me1, H3K4me3, H3K9ac and H3K27ac, as well as DNase I sensitivity, show conclusively that the log-posterior odds score consistently outperforms a simple binary filter based on the same data. We also show that our approach performs competitively with a more complex method, CENTIPEDE, and suggest that the relative simplicity of the log-posterior odds scoring method makes it an appealing and very general method for identifying functional TFBSs on the basis of DNA and epigenetic evidence.