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In silico labeling reveals the time-dependent label half-life and transit-time in dynamical systems

机译:电子标签显示动态系统中与时间有关的标签半衰期和传输时间

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摘要

BackgroundMathematical models of dynamical systems facilitate the computation of characteristic properties that are not accessible experimentally. In cell biology, two main properties of interest are (1) the time-period a protein is accessible to other molecules in a certain state - its half-life - and (2) the time it spends when passing through a subsystem - its transit-time. We discuss two approaches to quantify the half-life, present the novel method of in silico labeling, and introduce the label half-life and label transit-time. The developed method has been motivated by laboratory tracer experiments. To investigate the kinetic properties and behavior of a substance of interest, we computationally label this species in order to track it throughout its life cycle. The corresponding mathematical model is extended by an additional set of reactions for the labeled species, avoiding any double-counting within closed circuits, correcting for the influences of upstream fluxes, and taking into account combinatorial multiplicity for complexes or reactions with several reactants or products. A profile likelihood approach is used to estimate confidence intervals on the label half-life and transit-time.
机译:背景技术动态系统的数学模型有助于计算实验无法访问的特性。在细胞生物学中,感兴趣的两个主要属性是(1)某种蛋白质在某种状态下可被其他分子接近的时间-其半衰期-(2)通过子系统时所花费的时间-其转运-时间。我们讨论了两种量化半衰期的方法,介绍了计算机标记的新方法,并介绍了标签半衰期和标签传递时间。实验室示踪剂实验激发了开发的方法。为了研究目标物质的动力学特性和行为,我们在计算上标记了该物质,以便在整个生命周期中对其进行追踪。相应的数学模型通过针对标记物质的另一组反应扩展,避免了闭合回路内的任何重复计数,校正了上游通量的影响,并考虑了配合物或与多种反应物或产物的反应的组合多重性。轮廓似然方法用于估计标签半衰期和运输时间的置信区间。

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