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A computational method to preclude multistationarity in networks of interacting species

机译:排除相互作用物种网络中多平稳性的一种计算方法

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摘要

Motivation: Modeling and analysis of complex systems are important aspects of understanding systemic behavior. In the lack of detailed knowledge about a system, we often choose modeling equations out of convenience and search the (high-dimensional) parameter space randomly to learn about model properties. Qualitative modeling sidesteps the issue of choosing specific modeling equations and frees the inference from specific properties of the equations. We consider classes of ordinary differential equation (ODE) models arising from interactions of species/entities, such as (bio) chemical reaction networks or ecosystems. A class is defined by imposing mild assumptions on the interaction rates. In this framework, we investigate whether there can be multiple positive steady states in some ODE models in a given class. Results: We have developed and implemented a method to decide whether any ODE model in a given class cannot have multiple steady states. The method runs efficiently on models of moderate size. We tested the method on a large set of models for gene silencing by sRNA interference and on two publicly available databases of biological models, KEGG and Biomodels. We recommend that this method is used as (i) a pre-screening step for selecting an appropriate model and (ii) for investigating the robustness of non-existence of multiple steady state for a given ODE model with respect to variation in interaction rates.
机译:动机:复杂系统的建模和分析是理解系统行为的重要方面。在缺乏有关系统的详细知识的情况下,我们经常出于方便的目的选择建模方程,并随机搜索(高维)参数空间以了解模型属性。定性建模避开了选择特定建模方程式的问题,并使推论摆脱了特定方程式的属性。我们考虑由物种/实体(例如(生物)化学反应网络或生态系统)相互作用产生的普通微分方程(ODE)模型的类别。通过对交互速率施加适度的假设来定义类别。在此框架中,我们调查给定类中的某些ODE模型中是否可以存在多个正稳态。结果:我们已经开发并实现了一种方法,用于确定给定类中的任何ODE模型是否不能具有多个稳态。该方法在中等大小的模型上有效运行。我们在通过sRNA干扰进行基因沉默的大量模型上以及在两个公开可用的生物学模型数据库KEGG和Biomodels上测试了该方法。我们建议将此方法用作(i)选择适当模型的预筛选步骤,以及(ii)对于给定的ODE模型,研究相互作用速率变化对多种稳态不存在的鲁棒性。

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