RNA Pol II transcription model and interpretation of GRO-seq data.
RNA Pol II transcription model and interpretation of GRO-seq data.
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RNA Pol II 转录模型和 GRO-seq 数据的解释。
DOI：
10.1007/s00285-016-1014-4
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发表时间：
2017
影响因子：
1.9
通讯作者：
Dowell,RobinD
中科院分区：
文献类型：
--
作者：
Lladser,ManuelE;Azofeifa,JosephG;Allen,MaryA;Dowell,RobinD
提出了一种混合模型和统计方法来解释来自新生转录测定的读段的分布，例如全局连续测序（GRO-seq）数据。该模型是注释不可知的，并利用了目前对RNA聚合酶II行为的理解。简单地说，它假设聚合酶加载在基因组内的关键位置（转录起始位点）。一旦加载，聚合酶保持在起始形式（具有一定概率）或转变成延伸形式（具有剩余概率）。该模型可以在全基因组范围内拟合，允许在每个不同的转录物上评估Pol II行为的模式。此外，它允许第一次有原则的方法来区分起始信号和延伸信号;特别是，它意味着用于计算暂停指数的数据驱动方法，暂停指数是一种常用的度量，可以告知RNA聚合酶II的行为。我们证明，这种方法改进了现有的GRO-seq数据分析，并揭示了一种新的生物学理解的影响敲低雄性特异性致死（MSL）复杂的果蝇。
A mixture model and statistical method is proposed to interpret the distribution of reads from a nascent transcriptional assay, such as global run-on sequencing (GRO-seq) data. The model is annotation agnostic and leverages on current understanding of the behavior of RNA polymerase II. Briefly, it assumes that polymerase loads at key positions (transcription start sites) within the genome. Once loaded, polymerase either remains in the initiation form (with some probability) or transitions into an elongating form (with the remaining probability). The model can be fit genome-wide, allowing patterns of Pol II behavior to be assessed on each distinct transcript. Furthermore, it allows for the first time a principled approach to distinguishing the initiation signal from the elongation signal; in particular, it implies a data driven method for calculating the pausing index, a commonly used metric that informs on the behavior of RNA polymerase II. We demonstrate that this approach improves on existing analyses of GRO-seq data and uncovers a novel biological understanding of the impact of knocking down the Male Specific Lethal (MSL) complex inDrosophilia melanogaster.