Most Permissive Semantics of Boolean Networks

As shown in (http://dx.doi.org/10.1101/2020.03.22.998377), the usual update modes of Boolean networks (BNs), including synchronous and (generalized) asynchronous, fail to capture behaviors introduced by multivalued refinements. Thus, update modes do not allow a correct abstract reasoning on dynamics of biological systems, as they may lead to reject valid BN models.This technical report lists the main definitions and properties of the most permissive semantics of BNs introduced in http://dx.doi.org/10.1101/2020.03.22.998377. This semantics meets with a correct abstraction of any multivalued refinements, with any update mode. It subsumes all the usual updating modes, while enabling new behaviors achievable by more concrete models. Moreover, it appears that classical dynamical analyzes of reachability and attractors have a simpler computational complexity:- reachability can be assessed in a polynomial number of iterations. The computation of iterations is in NP in the very general case, and is linear when local functions are monotonic, or with some usual representations of functions of BNs (binary decision diagrams, Petri nets, automata networks, etc.). Thus, reachability is in P with locally-monotonic BNs, and P$^{\text{NP}}$ otherwise (instead of being PSPACE-complete with update modes);- deciding wherever a configuration belongs to an attractor is in coNP with locally-monotonic BNs, and coNP$^{\text{coNP}}$ otherwise (instead of PSPACE-complete with update modes).Furthermore, we demonstrate that the semantics completely captures any behavior achievable with any multilevel or ODE refinement of the BN; and the semantics is minimal with respect to this model refinement criteria: to any most permissive trajectory, there exists a multilevel refinement of the BN which can reproduce it.In brief, the most permissive semantics of BNs enables a correct abstract reasoning on dynamics of BNs, with a greater tractability than previously introduced update modes

Access Control Synthesis for Physical Spaces

Access-control requirements for physical spaces, like office buildings and airports, are best formulated from a global viewpoint in terms of system-wide requirements. For example, "there is an authorized path to exit the building from every room." In contrast, individual access-control components, such as doors and turnstiles, can only enforce local policies, specifying when the component may open. In practice, the gap between the system-wide, global requirements and the many local policies is bridged manually, which is tedious, error-prone, and scales poorly. We propose a framework to automatically synthesize local access control policies from a set of global requirements for physical spaces. Our framework consists of an expressive language to specify both global requirements and physical spaces, and an algorithm for synthesizing local, attribute-based policies from the global specification. We empirically demonstrate the framework's effectiveness on three substantial case studies. The studies demonstrate that access control synthesis is practical even for complex physical spaces, such as airports, with many interrelated security requirements

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

International audienceBoolean networks model finite discrete dynamical systems with complex behaviours. 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

Non-Deterministic Updates of Boolean Networks

Boolean networks are discrete dynamical systems where each automaton has its own Boolean function for computing its state according to the configuration of the network. The updating mode then determines how the configuration of the network evolves over time. Many of updating modes from the literature, including synchronous and asynchronous modes, can be defined as the composition of elementary deterministic configuration updates, i.e., by functions mapping configurations of the network. Nevertheless, alternative dynamics have been introduced using ad-hoc auxiliary objects, such as that resulting from binary projections of Memory Boolean networks, or that resulting from additional pseudo-states for Most Permissive Boolean networks. One may wonder whether these latter dynamics can still be classified as updating modes of finite Boolean networks, or belong to a different class of dynamical systems. In this paper, we study the extension of updating modes to the composition of non-deterministic updates, i.e., mapping sets of finite configurations. We show that the above dynamics can be expressed in this framework, enabling a better understanding of them as updating modes of Boolean networks. More generally, we argue that non-deterministic updates pave the way to a unifying framework for expressing complex updating modes, some of them enabling transitions that cannot be computed with elementary and non-elementary deterministic updates

Linear cuts in Boolean networks

Boolean networks are popular tools for the exploration of qualitative dynamical properties of biological systems. Several dynamical interpretations have been proposed based on the same logical structure that captures the interactions between Boolean components. They reproduce, in different degrees, the behaviours emerging in more quantitative models. In particular, regulatory conflicts can prevent the standard asynchronous dynamics from reproducing some trajectories that might be expected upon inspection of more detailed models. We introduce and study the class of networks with linear cuts, where linear components -- intermediates with a single regulator and a single target -- eliminate the aforementioned regulatory conflicts. The interaction graph of a Boolean network admits a linear cut when a linear component occurs in each cycle and in each path from components with multiple targets to components with multiple regulators. Under this structural condition the attractors are in one-to-one correspondence with the minimal trap spaces, and the reachability of attractors can also be easily characterized. Linear cuts provide the base for a new interpretation of the Boolean semantics that captures all behaviours of multi-valued refinements with regulatory thresholds that are uniquely defined for each interaction, and contribute a new approach for the investigation of behaviour of logical models

Solving XCSP problems by using Gecode

Gecode is one of the most efficient libraries that can be used for constraint solving. However, using it requires dealing with C++ programming details. On the other hand several formats for representing constraint networks have been proposed. Among them, XCSP has been proposed as a format based on XML which allows us to represent constraints defined either extensionally or intensionally, permits global constraints and has been the standard format of the international competition of constraint satisfaction problems solvers. In this paper we present a plug-in for solving problems specified in XCSP by exploiting the Gecode solver. This is done by dynamically translating constraints into Gecode library calls, thus avoiding the need to interact with C++.Comment: 5 pages, http://ceur-ws.org/Vol-810 CILC 201

Dépliages et interprétation abstraite pour réseaux de régulation biologiques paramétrés

The analysis of dynamics of biological regulatory networks, notably signalling and gene regulatory networks, faces the uncertainty of the exact computational model. Indeed, most of the knowledge available concerns the existence of (possibly indirect) interactions between biological entities (species), e.g. proteins, RNAs, genes, etc. The details on how different regulators of a same target cooperate, and even more so on consistent rates for those interactions, however, are rarely available. In this regard, qualitative modelling approaches in the form of discrete regulatory networks, such as Boolean and Thomas networks, offer an appropriate level of abstraction for the biological regulatory network dynamics. As discrete regulatory networks are based on an influence graph, they require few additional parameters compared to classical quantitative models. Nevertheless, determining the discrete parameters is a well known challenge, and a major bottleneck for providing robust predictions from computational models.The influence graph of a regulatory network establishes dependencies for the evolution of each specie, specified by the directed edges of the graph. The dependencies alone, however, do not suffice to specify the logical function governing the evolution of a specie. Instead the logical functions associated to each specie, constrained by the influence graph, are encoded within the parameters of a discrete regulatory network. The space of admissible logical functions is then represented by a parametric regulatory network. On the one hand, parametric regulatory networks can be used for identification of parameter values for which the resulting discrete regulatory network satisfies given (dynamical) properties. Parameter identification of regulatory networks can thus be seen as a particular instance of model synthesis, in the constrained setting of the underlying influence graph. On the other hand, parametric regulatory networks may be analysed as a stand-alone model, for making predictions that are robust with respect to variability in the network.The analysis of parametric regulatory network dynamics is hampered by dual combinatorial explosion, of the state space and of the parameter space. In this thesis, we develop novel methods of parametric regulatory network analysis, in the form of specialised semantics, aimed at alleviating the combinatorial explosion. First, we introduce abstract interpretation for the set of admissible parameter evaluations (parametrisations).The abstraction allows us to represent any set of parametrisations by a constant size encoding, at the cost of a conservative over-approximation. Second, we lift partial order semantics in the form of unfolding from Petri nets to parametric regulatory networks. The influence graphs of biological regulatory networks tend to be relatively sparse, allowing for a lot of concurrency. This can be harnessed by partial order reduction methods to produce concise state space representations.The two approaches are aimed at tackling both aspects of the dual combinatorial explosion and are introduced in a compatible manner, allowing one to employ them simultaneously. Such application is supported by a prototype implementation used to conduct experiments on various parametric regulatory networks. We further consider refinements of the methods, such as an on-the-run model reduction method lifted to parametric regulatory networks from automata networks.L'analyse de la dynamique des réseaux de régulation biologique, notamment des réseaux de signalisation et de régulation génique, fait face à l'incertitude du modèle de calcul exact. En effet, la plupart des connaissances disponibles concernent l'existence d'interactions (éventuellement indirectes) entre des entités biologiques (espèces), par ex. protéines, ARN, gènes, etc. Les détails sur la manière dont les différents régulateurs d'une même cible coopèrent, et plus encore sur les taux cohérents pour ces interactions, sont cependant rarement disponibles. A cet égard, des approches de modélisation qualitative sous forme de réseaux de régulation discrets, tels que les réseaux booléens et Thomas, offrir un niveau d'abstraction approprié pour la dynamique du réseau de régulation biologique. Les réseaux de régulation discrets étant basés sur un graphe d'influence, ils nécessitent peu de paramètres supplémentaires par rapport aux modèles quantitatifs classiques. Néanmoins, la détermination des paramètres discrets est un défi bien connu et un goulot d'étranglement majeur pour fournir des prédictions robustes à partir de modèles informatiques.Le graphe d'influence d'un réseau de régulation établit des dépendances pour l'évolution de chaque espèce, spécifiées par les arêtes dirigées du graphe. Les dépendances seules, cependant, ne suffisent pas pour spécifier la fonction logique régissant l'évolution d'une espèce. Au lieu de cela, les fonctions logiques associées à chaque espèce, contraintes par le graphe d'influence, sont codées dans les paramètres d'un réseau de régulation discret. L'espace des fonctions logiques admissibles est alors représenté par un réseau de régulation paramétrique. D'une part, les réseaux de régulation paramétriques peuvent être utilisés pour l'identification de valeurs de paramètres pour lesquelles le réseau de régulation discret résultant satisfait des propriétés (dynamiques) données. L'identification des paramètres des réseaux de régulation peut ainsi être vue comme un exemple particulier de synthèse de modèle, dans le cadre contraint du graphe d'influence sous-jacent. D'autre part, les réseaux de régulation paramétriques peuvent être analysés comme un modèle autonome, pour faire des prédictions robustes vis-à-vis de la variabilité du réseau.L'analyse de la dynamique du réseau de régulation paramétrique est entravée par la double explosion combinatoire, de l'espace d'états et de l'espace des paramètres. Dans cette thèse, nous développons de nouvelles méthodes d'analyse de réseau de régulation paramétrique, sous forme de sémantique spécialisée, visant à atténuer l'explosion combinatoire. Tout d'abord, nous introduisons une interprétation abstraite de l'ensemble des évaluations de paramètres admissibles (paramétrisations). L'abstraction permet de représenter n'importe quel ensemble de paramétrisations par un encodage de taille constante, au prix d'une sur-approximation conservatrice. Deuxièmement, nous élevons la sémantique d'ordre partiel sous la forme d'un déploiement des réseaux de Petri vers des réseaux de régulation paramétriques. Les graphiques d'influence des réseaux de régulation biologique ont tendance à être relativement clairsemés, ce qui permet une grande concurrence. Cela peut être exploité par des méthodes de réduction d'ordre partiel pour produire des représentations d'espace d'état concises.Les deux approches visent à aborder les deux aspects de la double explosion combinatoire et sont introduites de manière compatible, ce qui permet de les utiliser simultanément. Une telle application est soutenue par une implémentation prototype utilisée pour mener des expériences sur divers réseaux de régulation paramétriques. Nous considérons en outre des raffinements des méthodes, comme une méthode de réduction de modèle à la volée portée aux réseaux de régulation paramétriques à partir de réseaux d'automates