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On the Boolean Network Theory of Datalog$^\neg$

Trinh, Van-Giang, Benhamou, Belaid, Soliman, Sylvain, Fages, François

arXiv.org Artificial Intelligence

Datalog$^\neg$ is a central formalism used in a variety of domains ranging from deductive databases and abstract argumentation frameworks to answer set programming. Its model theory is the finite counterpart of the logical semantics developed for normal logic programs, mainly based on the notions of Clark's completion and two-valued or three-valued canonical models including supported, stable, regular and well-founded models. In this paper we establish a formal link between Datalog$^\neg$ and Boolean network theory first introduced for gene regulatory networks. We show that in the absence of odd cycles in a Datalog$^\neg$ program, the regular models coincide with the stable models, which entails the existence of stable models, and in the absence of even cycles, we prove the uniqueness of stable partial models and regular models. This connection also gives new upper bounds on the numbers of stable partial, regular, and stable models of a Datalog$^\neg$ program using the cardinality of a feedback vertex set in its atom dependency graph. Interestingly, our connection to Boolean network theory also points us to the notion of trap spaces. In particular we show the equivalence between subset-minimal stable trap spaces and regular models.


Abstract Dialectical Frameworks are Boolean Networks (full version)

Heyninck, Jesse, Knorr, Matthias, Leite, João

arXiv.org Artificial Intelligence

Dialectical frameworks are a unifying model of formal argumentation, where argumentative relations between arguments are represented by assigning acceptance conditions to atomic arguments. Their generality allow them to cover a number of different approaches with varying forms of representing the argumentation structure. Boolean regulatory networks are used to model the dynamics of complex biological processes, taking into account the interactions of biological compounds, such as proteins or genes. These models have proven highly useful for comprehending such biological processes, allowing to reproduce known behaviour and testing new hypotheses and predictions in silico, for example in the context of new medical treatments. While both these approaches stem from entirely different communities, it turns out that there are striking similarities in their appearence. In this paper, we study the relation between these two formalisms revealing their communalities as well as their differences, and introducing a correspondence that allows to establish novel results for the individual formalisms.


Tackling Universal Properties of Minimal Trap Spaces of Boolean Networks

Riva, Sara, Lagniez, Jean-Marie, López, Gustavo Magaña, Paulevé, Loïc

arXiv.org Artificial Intelligence

Minimal trap spaces (MTSs) capture subspaces in which the Boolean dynamics is trapped, whatever the update mode. They correspond to the attractors of the most permissive mode. Due to their versatility, the computation of MTSs has recently gained traction, essentially by focusing on their enumeration. In this paper, we address the logical reasoning on universal properties of MTSs in the scope of two problems: the reprogramming of Boolean networks for identifying the permanent freeze of Boolean variables that enforce a given property on all the MTSs, and the synthesis of Boolean networks from universal properties on their MTSs. Both problems reduce to solving the satisfiability of quantified propositional logic formula with 3 levels of quantifiers ($\exists\forall\exists$). In this paper, we introduce a Counter-Example Guided Refinement Abstraction (CEGAR) to efficiently solve these problems by coupling the resolution of two simpler formulas. We provide a prototype relying on Answer-Set Programming for each formula and show its tractability on a wide range of Boolean models of biological networks.


Marker and source-marker reprogramming of Most Permissive Boolean networks and ensembles with BoNesis

Paulevé, Loïc

arXiv.org Artificial Intelligence

Boolean networks (BNs) are discrete dynamical systems with applications to the modeling of cellular behaviors. In this paper, we demonstrate how the software BoNesis can be employed to exhaustively identify combinations of perturbations which enforce properties on their fixed points and attractors. We consider marker properties, which specify that some components are fixed to a specific value. We study 4 variants of the marker reprogramming problem: the reprogramming of fixed points, of minimal trap spaces, and of fixed points and minimal trap spaces reachable from a given initial configuration with the most permissive update mode. The perturbations consist of fixing a set of components to a fixed value. They can destroy and create new attractors. In each case, we give an upper bound on their theoretical computational complexity, and give an implementation of the resolution using the BoNesis Python framework. Finally, we lift the reprogramming problems to ensembles of BNs, as supported by BoNesis, bringing insight on possible and universal reprogramming strategies. This paper can be executed and modified interactively.


Synthesis of Boolean Networks from Biological Dynamical Constraints using Answer-Set Programming

Chevalier, Stéphanie, Froidevaux, Christine, Paulevé, Loïc, Zinovyev, Andrei

arXiv.org Artificial Intelligence

The state of each component is determined by a Boolean function of the state of (a subset of) the components of the network. This paper addresses the synthesis of these Boolean functions from constraints on their domain and emerging dynamical properties of the resulting network. The dynamical properties relate to the existence and absence of trajectories between partially observed configurations, and to the stable behaviours (fixpoints and cyclic attractors). The synthesis is expressed as a Boolean satisfiability problem relying on Answer-Set Programming with a parametrized complexity, and leads to a complete non-redundant characterization of the set of solutions. Considered constraints are particularly suited to address the synthesis of models of cellular differentiation processes, as illustrated on a case study. The scalability of the approach is demonstrated on random networks with scale-free structures up to 100 to 1,000 nodes depending on the type of constraints.