Most organisms exhibit various endogenous oscillating behaviors which provide crucial information as to how the internal biochemical processes are connected and regulated. Understanding the molecular mechanisms behind these oscillators requires interdisciplinary efforts combining both biological and computer experiments, as the latter can complement the former by simulating perturbed conditions with higher resolution. Harmonizing the two types of experiment, however, poses significant statistical challenges due to identifiability issues, numerical instability, and ill behavior in high dimension. This article devises a new Bayesian calibration framework for oscillating biochemical models. The proposed Bayesian model is estimated using an advanced MCMC which can efficiently infer the parameter values that match the simulated and observed oscillatory processes. Also proposed is an approach to sensitivity analysis approach based on the intervention posterior. This approach measures the influence of individual parameters on the target process by utilizing the obtained MCMC samples as a computational tool. The proposed framework is illustrated with circadian oscillations observed in a filamentous fungus, Neurospora crassa.
翻译:大多数生物体都表现出各种内在振荡行为,它们为内部生化过程的联系和监管提供了重要信息。了解这些振荡器背后的分子机制需要将生物和计算机实验结合起来的跨学科努力,因为后者可以通过以更高分辨率模拟扰动条件来补充前者。然而,协调这两类实验在统计上提出了巨大的挑战,原因是可识别性问题、数字不稳定和高维度的不良行为。本文章为振荡生化模型设计了新的巴伊西亚校准框架。拟议的巴伊西亚模型使用先进的MCMC来估计,该模型可以有效地推断出与模拟和观测的振荡过程相匹配的参数值。还提出了一种基于干预外表的敏感度分析方法。这一方法通过将获得的MC样本用作计算工具,衡量单个参数对目标过程的影响。拟议的框架用在纤维性真菌(Neurospora cranassa)中观测到的硅状动物振荡图示。