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从实验核小体定位图谱中建模核小体位置分布。

Modeling nucleosome position distributions from experimental nucleosome positioning maps.

机构信息

Institute for Applied Computer Science, University of Applied Sciences Stralsund, Zur Schwedenschanze 15, Stralsund 18435, Germany and Deutsches Krebsforschungszentrum (DKFZ) & BioQuant, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.

出版信息

Bioinformatics. 2013 Oct 1;29(19):2380-6. doi: 10.1093/bioinformatics/btt404. Epub 2013 Jul 11.

Abstract

MOTIVATION

Recent experimental advancements allow determining positions of nucleosomes for complete genomes. However, the resulting nucleosome occupancy maps are averages of heterogeneous cell populations. Accordingly, they represent a snapshot of a dynamic ensemble at a single time point with an overlay of many configurations from different cells. To study the organization of nucleosomes along the genome and to understand the mechanisms of nucleosome translocation, it is necessary to retrieve features of specific conformations from the population average.

RESULTS

Here, we present a method for identifying non-overlapping nucleosome configurations that combines binary-variable analysis and a Monte Carlo approach with a simulated annealing scheme. In this manner, we obtain specific nucleosome configurations and optimized solutions for the complex positioning patterns from experimental data. We apply the method to compare nucleosome positioning at transcription factor binding sites in different mouse cell types. Our method can model nucleosome translocations at regulatory genomic elements and generate configurations for simulations of the spatial folding of the nucleosome chain.

AVAILABILITY

Source code, precompiled binaries, test data and a web-based test installation are freely available at http://bioinformatics.fh-stralsund.de/nucpos/

摘要

动机

最近的实验进展允许确定完整基因组中核小体的位置。然而,由此产生的核小体占有率图谱是异质细胞群体的平均值。因此,它们代表了在单个时间点上的动态集合的快照,其中叠加了来自不同细胞的许多构象。为了研究基因组中核小体的组织,并了解核小体易位的机制,有必要从群体平均值中检索特定构象的特征。

结果

在这里,我们提出了一种从实验数据中识别非重叠核小体构象的方法,该方法结合了二变量分析和蒙特卡罗方法以及模拟退火方案。通过这种方式,我们从实验数据中获得了特定的核小体构象和复杂定位模式的优化解决方案。我们应用该方法比较了不同小鼠细胞类型中转录因子结合位点处的核小体定位。我们的方法可以模拟调节基因组元件处的核小体易位,并生成用于核小体链空间折叠模拟的构象。

可用性

源代码、预编译二进制文件、测试数据和基于网络的测试安装可在 http://bioinformatics.fh-stralsund.de/nucpos/ 上免费获得。

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