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Transient chromatin properties revealed by polymer models and stochastic simulations constructed from Chromosomal Capture data

机译:通过染色体捕获数据构建的聚合物模型和随机模拟揭示了瞬态染色质特性

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摘要

Chromatin organization can be probed by Chromosomal Capture (5C) data, from which the encounter probability (EP) between genomic sites is presented in a large matrix. This matrix is averaged over a large cell population, revealing diagonal blocks called Topological Associating Domains (TADs) that represent a sub-chromatin organization. To study the relation between chromatin organization and gene regulation, we introduce a computational procedure to construct a bead-spring polymer model based on the EP matrix. The model permits exploring transient properties constrained by the statistics of the 5C data. To construct the polymer model, we proceed in two steps: first, we introduce a minimal number of random connectors inside restricted regions to account for diagonal blocks. Second, we account for long-range frequent specific genomic interactions. Using the constructed polymer, we compute the first encounter time distribution and the conditional probability of three key genomic sites. By simulating single particle trajectories of loci located on the constructed polymers from 5C data, we found a large variability of the anomalous exponent, used to interpret live cell imaging trajectories. The present polymer construction provides a generic tool to study steady-state and transient properties of chromatin constrained by some physical properties embedded in 5C data.
机译:可以通过染色体捕获(5C)数据探查染色质的组织,从中可以大矩阵显示基因组位点之间的相遇概率(EP)。该矩阵是在大量细胞群体中平均的,揭示了称为拓扑关联域(TAD)的对角线块,它们代表染色质亚结构。为了研究染色质组织与基因调控之间的关系,我们引入了一种计算程序,以基于EP矩阵构建珠-弹簧聚合物模型。该模型允许探索受5C数据统计约束的瞬态特性。要构建聚合物模型,我们分两步进行:首先,在受限区域内引入最少数量的随机连接器以解决对角线嵌段。其次,我们考虑了长期频繁的特定基因组相互作用。使用构建的聚合物,我们计算了三个关键基因组位点的首次遭遇时间分布和条件概率。通过从5C数据模拟位于构建的聚合物上的基因座的单粒子轨迹,我们发现异常指数的大变异性,可用于解释活细胞成像轨迹。本发明的聚合物结构提供了一种通用工具来研究染色质的稳态和瞬态特性,这些特性受嵌入5C数据中的某些物理特性的约束。

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