BACKGROUND Numerous cellular differentiation processes can be captured using discrete qualitative models of biological regulatory networks. These models describe the temporal evolution of the state of the network subject to different competing transitions, potentially leading the system to different attractors. This paper focusses on the formal identification of states and transitions that are crucial for preserving or pre-empting the reachability of a given behaviour. METHODS In the context of non-deterministic automata networks, we propose a static identification of so-called bifurcations, i.e., transitions after which a given goal is no longer reachable. Such transitions are naturally good candidates for controlling the occurrence of the goal, notably by modulating their propensity. Our method combines Answer-Set Programming with static analysis of reachability properties to provide an under-approximation of all the existing bifurcations. RESULTS We illustrate our discrete bifurcation analysis on several models of biological systems, for which we identify transitions which impact the reachability of given long-term behaviour. In particular, we apply our implementation on a regulatory network among hundreds of biological species, supporting the scalability of our approach. CONCLUSIONS Our method allows a formal and scalable identification of transitions which are responsible for the lost of capability to reach a given state. It can be applied to any asynchronous automata networks, which encompass Boolean and multi-valued models. An implementation is provided as part of the Pint software, available at http://loicpauleve.name/pint.

中文翻译：

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使用答案集编程识别生物调控网络中的分叉转变。

背景技术可以使用生物调节网络的离散定性模型来捕获许多细胞分化过程。这些模型描述了经受不同竞争转换的网络状态的时间演变，可能导致系统指向不同的吸引子。本文着重于对状态和转换的形式化识别，这对于保护或抢占给定行为的可及性至关重要。方法在非确定性自动机网络的背景下，我们提出了对所谓的分叉的静态识别，即分叉之后无法再达到给定目标的过渡。这样的过渡自然是控制目标发生的良好候选者，尤其是通过调节其倾向性。我们的方法将答案集编程与可达性属性的静态分析相结合，以提供所有现有分叉点的近似值。结果我们说明了对几种生物系统模型的离散分叉分析，我们确定了影响给定长期行为可达性的过渡。特别是，我们在数百种生物物种之间的监管网络上应用了我们的实施，从而支持了我们方法的可扩展性。结论我们的方法可以对过渡进行正式和可扩展的标识，这些过渡是导致失去达到给定状态的能力的原因。它可以应用于包含布尔和多值模型的任何异步自动机网络。作为Pint软件一部分提供的实现，可从http：// loicpauleve获得。