DANPOS: dynamic analysis of nucleosome position and occupancy by sequencing.

DANPOS: dynamic analysis of nucleosome position and occupancy by sequencing.
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DOI:
10.1101/gr.142067.112
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发表时间:
2013-02
期刊:
影响因子:
7
通讯作者:
Li W
Li W
中科院分区:
生物学1区
文献类型:
--
作者:
Chen K;Xi Y;Pan X;Li Z;Kaestner K;Tyler J;Dent S;He X;Li W

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下一代测序的最新发展使核小体组织的全基因组分析成为可能。虽然已经有几种从单一实验条件推断核小体位置的算法,但准确定义与环境变化相关的动态核小体仍然是一个挑战。在这里,我们报告了一个全面的生物信息学管道,DANPOS,明确设计用于单核苷酸分辨率的动态核小体分析。使用模拟和真实的核小体数据,我们表明,在初步的数据处理和最佳统计检验的偏差校正显着提高动态核小体的功能解释。DANPOS的单核苷酸分辨率分析使我们能够使用统一的统计框架来检测所有三类核小体动力学,例如位置偏移,future变化和占用变化。途径分析表明,每个类别都涉及不同的生物功能。我们还分析了测序深度的影响,并建议即使200倍的覆盖率可能不足以识别所有的动态核小体。最后,基于来自人类造血干细胞(HSC)和小鼠胚胎干细胞(ESC)的核小体数据,我们证明了DANPOS在定义功能性动态核小体方面也是稳健的,不仅在启动子中,而且在哺乳动物基因组的远端调控区中。
Recent developments in next-generation sequencing have enabled whole-genome profiling of nucleosome organizations. Although several algorithms for inferring nucleosome position from a single experimental condition have been available, it remains a challenge to accurately define dynamic nucleosomes associated with environmental changes. Here, we report a comprehensive bioinformatics pipeline, DANPOS, explicitly designed for dynamic nucleosome analysis at single-nucleotide resolution. Using both simulated and real nucleosome data, we demonstrated that bias correction in preliminary data processing and optimal statistical testing significantly enhances the functional interpretation of dynamic nucleosomes. The single-nucleotide resolution analysis of DANPOS allows us to detect all three categories of nucleosome dynamics, such as position shift, fuzziness change, and occupancy change, using a uniform statistical framework. Pathway analysis indicates that each category is involved in distinct biological functions. We also analyzed the influence of sequencing depth and suggest that even 200-fold coverage is probably not enough to identify all the dynamic nucleosomes. Finally, based on nucleosome data from the human hematopoietic stem cells (HSCs) and mouse embryonic stem cells (ESCs), we demonstrated that DANPOS is also robust in defining functional dynamic nucleosomes, not only in promoters, but also in distal regulatory regions in the mammalian genome.
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