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Model Discrimination in Dynamic Molecular Systems: Application to Parotid De-differentiation Network

机译:动态分子系统中的模型判别:在腮腺去分化网络中的应用

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摘要

>In modern systems biology the modeling of longitudinal data, such as changes in mRNA concentrations, is often of interest. Fully parametric, ordinary differential equations (ODE)-based models are typically developed for the purpose, but their lack of fit in some examples indicates that more flexible Bayesian models may be beneficial, particularly when there are relatively few data points available. However, under such sparse data scenarios it is often difficult to identify the most suitable model. The process of falsifying inappropriate candidate models is called model discrimination. We propose here a formal method of discrimination between competing Bayesian mixture-type longitudinal models that is both sensitive and sufficiently flexible to account for the complex variability of the longitudinal molecular data. The ideas from the field of Bayesian analysis of computer model validation are applied, along with modern Markov Chain Monte Carlo (MCMC) algorithms, in order to derive an appropriate Bayes discriminant rule. We restrict attention to the two-model comparison problem and present the application of the proposed rule to the mRNA data in the de-differentiation network of three mRNA concentrations in mammalian salivary glands as well as to a large synthetic dataset derived from the model used in the recent DREAM6 competition.
机译:>在现代系统生物学中,通常需要对纵向数据进行建模,例如mRNA浓度的变化。基于全参数,常微分方程(ODE)的模型通常是为此目的而开发的,但是在某些示例中它们的拟合不足表明,更灵活的贝叶斯模型可能是有益的,尤其是在可用数据点相对较少时。但是,在这种稀疏的数据场景下,通常很难确定最合适的模型。伪造不合适的候选模型的过程称为模型歧视。我们在这里提出了一种区分竞争的贝叶斯混合型纵向模型的正式方法,该方法既灵敏又足够灵活,可以解决纵向分子数据的复杂变异性。贝叶斯计算机模型验证分析领域的思想与现代马尔可夫链蒙特卡洛(MCMC)算法一起被应用,以得出合适的贝叶斯判别规则。我们将注意力集中在两个模型的比较问题上,并将拟议的规则应用于哺乳动物唾液腺中三种mRNA浓度的去分化网络中的mRNA数据,以及从该模型中使用的模型获得的大型合成数据集最近的DREAM6比赛

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