A cell size- and cell cycle-aware stochastic model for predicting time-dynamic gene network activity in individual cells.
A cell size- and cell cycle-aware stochastic model for predicting time-dynamic gene network activity in individual cells.
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DOI：
10.1186/s12918-015-0240-5
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发表时间：
2015-12-09
影响因子：
--
通讯作者：
Acar M
中科院分区：
文献类型：
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作者：
Song R;Peng W;Liu P;Acar M
尽管已经开发了多种建模方法来预测基因网络的活性，但考虑到细胞体积和细胞周期阶段的实时变化的时间动态随机模型仍然缺乏。在这里，我们提出了一个随机单细胞模型，它可以应用于任何具有任意数量组件的真核基因网络。该模型跟踪细胞体积、DNA复制和细胞分裂的变化，并根据这些信息动态调整随机反应的速率。通过跟踪细胞分裂，该模型可以维护细胞谱系信息，使研究人员能够追踪任何单个细胞的后代，从而研究细胞谱系效应。为了测试我们模型的预测能力，我们将其应用于酿酒酵母的典型半乳糖网络。使用最小的一组自由参数，并跨越几个半乳糖诱导条件，该模型有效地捕获了通过实验获得的单细胞网络活动水平以及表型转换率的几个细节。我们的模型可以很容易地定制来对任何常用细胞类型中的任何基因网络进行建模，为系统生物学领域提供了一种新颖且用户友好的随机建模能力。本文的在线版本(doi：10.1186/s12918-0150240-5)包含补充材料，授权用户可以使用。
Despite the development of various modeling approaches to predict gene network activity, a time dynamic stochastic model taking into account real-time changes in cell volume and cell cycle stages is still missing. Here we present a stochastic single-cell model that can be applied to any eukaryotic gene network with any number of components. The model tracks changes in cell volume, DNA replication, and cell division, and dynamically adjusts rates of stochastic reactions based on this information. By tracking cell division, the model can maintain cell lineage information, allowing the researcher to trace the descendants of any single cell and therefore study cell lineage effects. To test the predictive power of our model, we applied it to the canonical galactose network of the yeast Saccharomyces cerevisiae. Using a minimal set of free parameters and across several galactose induction conditions, the model effectively captured several details of the experimentally-obtained single-cell network activity levels as well as phenotypic switching rates. Our model can readily be customized to model any gene network in any of the commonly used cells types, offering a novel and user-friendly stochastic modeling capability to the systems biology field. The online version of this article (doi:10.1186/s12918-015-0240-5) contains supplementary material, which is available to authorized users.