S. Caligola, Tommaso Carlucci, F. Fummi, C. Laudanna, G. Constantin, N. Bombieri, R. Giugno
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引用次数: 1
摘要
随机Petri网(Stochastic Petri nets, SPN)是Petri网的一种形式,其中的转换在一个概率和随机确定的延迟后启动。由于它们能够将随机性纳入模型并考虑到可能的波动和环境噪声,因此被广泛应用。在系统生物学中,它们正在成为模拟代谢网络的参考形式,其中环境中分子相互作用引起的噪声起着至关重要的作用。提出了一些框架来实现和动态模拟SPN。然而,它们不允许自动模型参数化,这是识别导致模型满足模型时间属性的网络配置的关键任务。本文提出了一个将SPN模型综合为SystemC代码的框架。该框架允许用户正式定义要观察的网络属性,并通过基于断言的验证(ABV)自动推断导致网络满足这些属性的参数配置。我们应用该框架来实现和模拟一个复杂的生物网络,即嘌呤代谢,目的是再现从体外获得的代谢组学数据,这些数据来自与实验性自身免疫性疾病诱导有关的幼稚淋巴细胞和自身反应性T细胞。
Efficient Simulation and Parametrization of Stochastic Petri Nets in SystemC: A Case study from Systems Biology
Stochastic Petri nets (SPN) are a form of Petri net where the transitions fire after a probabilistic and randomly determined delay. They are adopted in a wide range of applications thanks to their capability of incorporating randomness in the models and taking into account possible fluctuations and environmental noise. In Systems Biology, they are becoming a reference formalism to model metabolic networks, in which the noise due to molecule interactions in the environment plays a crucial role. Some frameworks have been proposed to implement and dynamically simulate SPN. Nevertheless, they do not allow for automatic model parametrization, which is a crucial task to identify the network configurations that lead the model to satisfy temporal properties of the model. This paper presents a framework that synthesizes the SPN models into SystemC code. The framework allows the user to formally define the network properties to be observed and to automatically extrapolate, through Assertion-based Verification (ABV), the parameter configurations that lead the network to satisfy such properties. We applied the framework to implement and simulate a complex biological network, i.e., the purine metabolism, with the aim of reproducing the metabolomics data obtained in-vitro from naive lymphocytes and autoreactive T cells implicated in the induction of experimental autoimmune disorders.