DANPOS: dynamic analysis of nucleosome position and occupancy by sequencing

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 a...

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Bibliographic Details
Published in:Genome research 2013-02, Vol.23 (2), p.341-351
Main Authors: Chen, Kaifu, Xi, Yuanxin, Pan, Xuewen, Li, Zhaoyu, Kaestner, Klaus, Tyler, Jessica, Dent, Sharon, He, Xiangwei, Li, Wei
Format: Article
Language:English
Subjects:
Algorithms
Animals
Computational Biology - methods
Computer Simulation
Databases, Genetic
DNA - metabolism
High-Throughput Nucleotide Sequencing
Humans
Method
Mice
Nucleosomes - metabolism
Promoter Regions, Genetic
Protein Binding
ROC Curve
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Summary: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.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.142067.112