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Model Checking Tap Withdrawal in C. Elegans

机译:C. Elegans中的模型检查抽头抽出

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We present what we believe to be the first formal verification of a biologically realistic (nonlinear ODE) model of a neural circuit in a multicellular organism: Tap Withdrawal (TW) in C. Elegans, the common roundworm. TW is a reflexive behavior exhibited by C. Elegans in response to vibrating the surface on which it is moving; the neural circuit underlying this response is the subject of this investigation. Specially, we perform reach-tube-based reachability analysis on the TW circuit model of Wicks et al. (1996) to estimate key model parameters. Underlying our approach is the use of Fan and Mitra's recently developed technique for automatically computing local discrepancy (convergence and divergence rates) of general nonlinear systems. The results we obtain are a significant extension of those of Wicks et al. (1996), who equip their model with fixed parameter values that reproduce the predominant TW response they observed experimentally in a population of 590 worms. In contrast, our techniques allow us to much more fully explore the model's parameter space, identifying in the process the parameter ranges responsible for the predominant behavior as well as the non-dominant ones. The verification framework we developed to conduct this analysis is model-agnostic, and can thus be re-used on other complex nonlinear systems.
机译:我们提出了我们认为是对多细胞生物中神经回路的生物现实(非线性ODE)模型的首次正式验证:C. Elegans(常见round虫)的抽头抽提(TW)。 TW是C. Elegans对震动其移动的表面所表现出的反射行为。该反应背后的神经回路是本研究的主题。特别是,我们对Wicks等人的TW电路模型执行基于可达管的可达性分析。 (1996)估计关键模型参数。我们的方法的基础是使用Fan和Mitra最近开发的技术来自动计算一般非线性系统的局部差异(收敛和发散率)。我们获得的结果是Wicks等人的结果的重要扩展。 (1996年),他们为模型配备了固定的参数值,这些参数值可再现他们在590个蠕虫种群中实验观察到的主要TW响应。相比之下,我们的技术使我们能够更全面地探索模型的参数空间,在此过程中确定负责主要行为和非主要行为的参数范围。我们开发的用于执行此分析的验证框架与模型无关,因此可以在其他复杂的非线性系统上重复使用。

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