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时间采样分辨率对生物传输模型参数推断的影响。

The impact of temporal sampling resolution on parameter inference for biological transport models.

机构信息

Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom.

出版信息

PLoS Comput Biol. 2018 Jun 25;14(6):e1006235. doi: 10.1371/journal.pcbi.1006235. eCollection 2018 Jun.

Abstract

Imaging data has become an essential tool to explore key biological questions at various scales, for example the motile behaviour of bacteria or the transport of mRNA, and it has the potential to transform our understanding of important transport mechanisms. Often these imaging studies require us to compare biological species or mutants, and to do this we need to quantitatively characterise their behaviour. Mathematical models offer a quantitative description of a system that enables us to perform this comparison, but to relate mechanistic mathematical models to imaging data, we need to estimate their parameters. In this work we study how collecting data at different temporal resolutions impacts our ability to infer parameters of biological transport models by performing exact inference for simple velocity jump process models in a Bayesian framework. The question of how best to choose the frequency with which data is collected is prominent in a host of studies because the majority of imaging technologies place constraints on the frequency with which images can be taken, and the discrete nature of observations can introduce errors into parameter estimates. In this work, we mitigate such errors by formulating the velocity jump process model within a hidden states framework. This allows us to obtain estimates of the reorientation rate and noise amplitude for noisy observations of a simple velocity jump process. We demonstrate the sensitivity of these estimates to temporal variations in the sampling resolution and extent of measurement noise. We use our methodology to provide experimental guidelines for researchers aiming to characterise motile behaviour that can be described by a velocity jump process. In particular, we consider how experimental constraints resulting in a trade-off between temporal sampling resolution and observation noise may affect parameter estimates. Finally, we demonstrate the robustness of our methodology to model misspecification, and then apply our inference framework to a dataset that was generated with the aim of understanding the localization of RNA-protein complexes.

摘要

成像数据已成为探索各种尺度上关键生物学问题的重要工具,例如细菌的运动行为或 mRNA 的运输,并且有可能改变我们对重要运输机制的理解。通常,这些成像研究需要我们比较生物物种或突变体,而为了做到这一点,我们需要定量描述它们的行为。数学模型为系统提供了定量描述,使我们能够进行这种比较,但是要将机械数学模型与成像数据相关联,我们需要估计它们的参数。在这项工作中,我们通过在贝叶斯框架中对简单的速度跳跃过程模型进行精确推断,研究了以不同时间分辨率收集数据如何影响我们推断生物运输模型参数的能力。在许多研究中,如何选择最佳数据收集频率的问题非常突出,因为大多数成像技术对可以拍摄图像的频率施加了限制,并且观察的离散性质可能会给参数估计带来误差。在这项工作中,我们通过在隐藏状态框架中构建速度跳跃过程模型来减轻这些误差。这使我们能够获得简单速度跳跃过程的噪声观测的重新定向率和噪声幅度的估计值。我们证明了这些估计值对采样分辨率的时间变化和测量噪声的程度的敏感性。我们使用我们的方法为旨在描述可以通过速度跳跃过程来描述的运动行为的研究人员提供实验指南。特别是,我们考虑了由于时间采样分辨率和观察噪声之间的权衡而导致的实验限制可能如何影响参数估计。最后,我们证明了我们的方法对模型失配的鲁棒性,然后将我们的推断框架应用于旨在了解 RNA-蛋白质复合物定位的数据集。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/335f/6034909/6ee77c24919e/pcbi.1006235.g001.jpg

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