A DYNAMIC BAYESIAN NETWORK FOR IDENTIFYING PROTEIN BINDING FOOTPRINTS FROM SINGL

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 动机：转录因子结合位点(TFBs)的全球图谱对于理解基因调控和基因组功能至关重要。染色质的DNaseI消化与大规模并行测序(数字基因组足迹)相结合，能够在全基因组范围内以高分辨率识别蛋白质结合足迹。然而，准确推断这些足迹的位置仍然是一个具有挑战性的计算问题。 结果：我们提出了一种基于动态贝叶斯网络的方法，用于从数字基因组足迹数据中识别和分配蛋白质结合足迹的统计置信度估计。该方法，DBFP，允许在概率框架中识别足迹，并在固定召回率下在精度方面优于我们之前描述的算法。应用于来自酿酒酵母的数字足迹数据集，DBFP识别出4679个在基因间区具有统计意义的足迹。这些足迹主要位于转录起始点附近，对已知的TFBS具有强烈的富集性。不含已知基序的足迹优先位于其他足迹的近端，与这些足迹的合作结合一致。DBFP还鉴定了酵母编码区中一组具有统计学意义的足迹。这些足迹中的许多与反义转录本的边界一致，最重要的足迹富含染色质相关因子Abf1和Rap1的结合位点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Motivation: A global map of transcription factor binding sites (TFBSs) is critical to understanding gene regulation and genome function. DNaseI digestion of chromatin coupled with massively parallel sequencing (digital genomic footprinting) enables the identification of protein-binding footprints with high resolution on a genome-wide scale. However, accurately inferring the locations of these footprints remains a challenging computational problem. Results: We present a dynamic Bayesian network-based approach for the identification and assignment of statistical confidence estimates to protein-binding footprints from digital genomic footprinting data. The method, DBFP, allows footprints to be identified in a probabilistic framework and outperforms our previously described algorithm in terms of precision at a fixed recall. Applied to a digital footprinting data set from Saccharomyces cerevisiae, DBFP identifies 4679 statistically significant footprints within intergenic regions. These footprints are mainly located near transcription start sites and are strongly enriched for known TFBSs. Footprints containing no known motif are preferentially located proximal to other footprints, consistent with cooperative binding of these footprints. DBFP also identifies a set of statistically significant footprints in the yeast coding regions. Many of these footprints coincide with the boundaries of antisense transcripts, and the most significant footprints are enriched for binding sites of the chromatin-associated factors Abf1 and Rap1.