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Automated mapping of large-scale chromatin structure in ENCODE

机译:在ENCODE中自动映射大规模染色质结构

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Motivation: A recently developed DNasel assay has given us our first genome-wide view of chromatin structure. In addition to cataloging DNasel hypersensitive sites, these data allows us to more completely characterize overall features of chromatin accessibility. We employed a Bayesian hierarchical change-point model (CPM), a generalization of a hidden Markov Model (HMM), to characterize tiled microarray DNasel sensitivity data available from the ENCODE project.Results: Our analysis shows that the accessibility of chromatin to cleavage by DNasel is well described by a four state model of local segments with each state described by a continuous mixture of Gaussian variables. The CPM produces a better fit to the observed data than the HMM. The large posterior probability for the four-state CPM suggests that the data falls naturally into four classes of regions, which we call major and minor DNasel hypersensitive sites (DHSs), regions of intermediate sensitivity, and insensitive regions. These classes agree well with a model of chromatin in which local disruptions (DHSs) are concentrated within larger domains of intermediate sensitivity, the accessibility islands. The CPM assigns 92 of the bases within the ENCODE regions to the insensitive regions. The 5.8 of the bases that are in regions of intermediate sensitivity are clearly enriched in functional elements, including genes and activating histone modifications, while the remaining 2.2 of the bases in hypersensitive regions are very strongly enriched in these elements.
机译:动机:最近开发的DNasel分析为我们提供了染色质结构的第一个全基因组视野。除了对DNasel高敏部位进行分类外,这些数据还使我们能够更完整地表征染色质可及性的总体特征。我们使用贝叶斯分层变化点模型(CPM)(一种隐马尔可夫模型(HMM)的概括)来表征ENCODE项目提供的平铺微阵列DNasel敏感​​性数据。结果:我们的分析表明,染色质可通过以下方式裂解DNasel通过局部片段的四状态模型很好地描述,每种状态都由高斯变量的连续混合描述。 CPM比HMM更好地拟合了观测数据。四态CPM的后验概率很大,表明数据自然地分为四类区域,我们将其称为主要和次要DNasel超敏感位点(DHS),中等敏感度区域和不敏感区域。这些类别与染色质模型非常吻合,其中局部干扰(DHS)集中在中等敏感性的较大域(可访问性岛)内。 CPM将ENCODE区域内的92个碱基分配给不敏感区域。在中等敏感性区域中的5.8个碱基显然富含功能性元素,包括基因和激活组蛋白修饰,而在超敏性区域中的其余2.2个碱基则非常强烈地富含这些元素。

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