论文标题

自相关的测量过程和生物系统普通微分方程模型的推断

Autocorrelated measurement processes and inference for ordinary differential equation models of biological systems

论文作者

Lambert, Ben, Lei, Chon Lok, Robinson, Martin, Clerx, Michael, Creswell, Richard, Ghosh, Sanmitra, Tavener, Simon, Gavaghan, David

论文摘要

普通的微分方程模型用于描述生物学跨生物学的动态过程。要对这些模型进行基于似然的参数推断,必须指定一个统计过程,该过程表示数学模型中未明确包含的因素的贡献。为此,通常会选择独立的高斯噪声,因此其使用情况很广泛,因此研究人员通常没有为此选择提供明确的理由。该噪声模型假设“随机”潜在因素以短暂的方式影响系统,从而导致可观察到的模型对应物的非系统性偏差。但是,像系统的确定性建模部分一样,这些潜在因素可能会对观察物产生持续的影响。在这里,我们使用从心脏生理和电化学中得出的动力学系统的实验数据,以证明观察值和建模数量之间的高度持久差异可能发生。考虑到仅由于测量缺陷而产生持续噪声的情况,我们使用Fisher信息矩阵来量化参数估计的不确定性在错误地假设独立噪声时人为地降低。我们提出一个工作流程,以诊断模型拟合中的持续噪声,并描述如何重塑相关错误。

Ordinary differential equation models are used to describe dynamic processes across biology. To perform likelihood-based parameter inference on these models, it is necessary to specify a statistical process representing the contribution of factors not explicitly included in the mathematical model. For this, independent Gaussian noise is commonly chosen, with its use so widespread that researchers typically provide no explicit justification for this choice. This noise model assumes `random' latent factors affect the system in ephemeral fashion resulting in unsystematic deviation of observables from their modelled counterparts. However, like the deterministically modelled parts of a system, these latent factors can have persistent effects on observables. Here, we use experimental data from dynamical systems drawn from cardiac physiology and electrochemistry to demonstrate that highly persistent differences between observations and modelled quantities can occur. Considering the case when persistent noise arises due only to measurement imperfections, we use the Fisher information matrix to quantify how uncertainty in parameter estimates is artificially reduced when erroneously assuming independent noise. We present a workflow to diagnose persistent noise from model fits and describe how to remodel accounting for correlated errors.

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