arXiv subjects

Loïc Paulevé

Publications and source records attributed to Loïc Paulevé.

At least 19 recordsLinked to original sources

arXiv2026

Bringing memory to Boolean networks: a unifying framework

Boolean networks are extensively applied as models of complex dynamical systems, aiming at capturing essential features related to causality and synchronicity of the state changes of components along time. Dynamics of Boolean networks result from the application of their Boolean map according to a so-called update mode, specifying the possible transitions between network configurations. In this paper, we explore update modes that possess a memory on past configurations, and provide a generic framework to define them. We show that recently introduced modes such as the most permissive and interval modes can be naturally expressed in this framework, and we propose novel update modes, the history-based, trapping, and subcube-based modes. Building on the unified definitions, we provide a comprehensive comparison of memory-based update modes, resulting in their hierarchy by simulation and weak simulation. Finally, we highlight consequences of introducing memory on the notions of trajectory and attractors.

cs.LO↗

arXiv2026

A Bilevel Integer Programming Approach for the Synchronous Attractor Control Problem

Boolean networks are dynamical models of disease development in which the activation levels of genes are represented by binary variables. Given a Boolean network, controls represent mutations or medical treatments that fix the activation levels of selected genes so that all states in every attractor (i.e., long-term recurrent states) satisfy a desired phenotype. Our goal is to enumerate all minimal controls, identifying critical gene subsets in disease development and therapy. This problem has an inherent bilevel integer programming structure and is computationally challenging. We propose an infeasibility-based Benders decomposition, a logic-based Benders framework for bilevel integer programs with multiple subproblems. In our application, each subproblem finds a forbidden attractor of a given length and yields a problem-specific feasibility cut. We also propose an auxiliary IP called subspace separation that finds a Boolean subspace that includes multiple forbidden attractors and thereby strengthens the cut. Numerical experiments show that the resulting algorithms are much more scalable than state-of-the-art methods and that subspace separation substantially improves performance.

math.OC↗

arXiv2026

Prediction of source nutrients for microorganisms using metabolic networks

Metagenomics has lowered the barrier to microbial discovery--enabling the identification of novel microbes without isolation--but cultures remain imperative for the deep study of microbes. Cultivation and isolation of non-model microbes remains a major challenge, despite advances in high-throughput culturomic methods. The quantity of simultaneous experimental variables is constrained by time and resources, but the list can be reduced using computational biology. Given an annotated genome, metabolic modelling can be used to predict source nutrients required for the growth of a microbe, which acts as an initial screen to inform culture and isolation experiments. This chapter provides an overview of metabolic networks and modelling and how they can be used to predict the nutrient requirements of a microorganism, followed by a sample protocol using a toy metabolic network, which is then expanded to a genome-scale metabolic network application. These methods can be applied to any metabolic network of interest--which in turn can be created from any genome of interest--and are a starting point for experimental validation of source nutrients required for microorganisms that remain uncultivated to date.

q-bio.MN↗

arXiv2024

Phenotype control and elimination of variables in Boolean networks

We investigate how elimination of variables can affect the asymptotic dynamics and phenotype control of Boolean networks. In particular, we look at the impact on minimal trap spaces, and identify a structural condition that guarantees their preservation. We examine the possible effects of variable elimination under three of the most popular approaches to control (attractor-based control, value propagation and control of minimal trap spaces), and under different update schemes (synchronous, asynchronous, generalized asynchronous). We provide some insights on the application of reduction, and an ample inventory of examples and counterexamples.

cs.DM↗

arXiv2024

mpbn: a simple tool for efficient edition and analysis of elementary properties of Boolean networks

The tool mpbn offers a Python programming interface for an easy interactive editing of Boolean networks and the efficient computation of elementary properties of their dynamics, including fixed points, trap spaces, and reachability properties under the Most Permissive update mode. Relying on Answer-Set Programming logical framework, we show that mpbn is scalable to models with several thousands of nodes and is one of the best-performing tool for computing minimal and maximal trap spaces of Boolean networks, a key feature for understanding and controling their stable behaviors. The tool is available at https://github.com/bnediction/mpbn.

cs.LO↗

arXiv2023

Tackling Universal Properties of Minimal Trap Spaces of Boolean Networks

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.

cs.LO↗

arXiv2023

Attractor identification in asynchronous Boolean dynamics with network reduction

Identification of attractors, that is, stable states and sustained oscillations, is an important step in the analysis of Boolean models and exploration of potential variants. We describe an approach to the search for asynchronous cyclic attractors of Boolean networks that exploits, in a novel way, the established technique of elimination of components. Computation of attractors of simplified networks allows the identification of a limited number of candidate attractor states, which are then screened with techniques of reachability analysis combined with trap space computation. An implementation that brings together recently developed Boolean network analysis tools, tested on biological models and random benchmark networks, shows the potential to significantly reduce running times.

cs.DM↗

arXiv2023

Computational Complexity of Minimal Trap Spaces in Boolean Networks

A Boolean network (BN) is a discrete dynamical system defined by a Boolean function that maps to the domain itself. A trap space of a BN is a generalization of a fixed point, which is defined as the sub-hypercubes closed by the function of the BN. A trap space is minimal if it does not contain any smaller trap space. Minimal trap spaces have applications for the analysis of attractors of BNs with various update modes. This paper establishes the computational complexity results of three decision problems related to minimal trap spaces: the decision of the trap space property of a sub-hypercube, the decision of its minimality, and the decision of the membership of a given configuration to a minimal trap space. Under several cases on Boolean function representations, we investigate the computational complexity of each problem. In the general case, we demonstrate that the trap space property is coNP-complete, and the minimality and the membership properties are $Π_2^{\text P}$-complete. The complexities drop by one level in the polynomial hierarchy whenever the local functions of the BN are either unate, or are represented using truth-tables, binary decision diagrams, or double DNFs (Petri net encoding): the trap space property can be decided in a polynomial time, whereas deciding the minimality and the membership are coNP- complete. When the BN is given as its functional graph, all these problems are in P.

cs.DM↗

arXiv2023

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

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.

eess.SY↗

arXiv2022

Avoid One's Doom: Finding Cliff-Edge Configurations in Petri Nets

A crucial question in analyzing a concurrent system is to determine its long-run behaviour, and in particular, whether there are irreversible choices in its evolution, leading into parts of the reachability space from which there is no return to other parts. Casting this problem in the unifying framework of safe Petri nets, our previous work has provided techniques for identifying attractors, i.e. terminal strongly connected components of the reachability space, whose attraction basins we wish to determine. Here, we provide a solution for the case of safe Petri nets. Our algorithm uses net unfoldings and provides a map of all of the system's configurations (concurrent executions) that act as cliff-edges, i.e. any maximal extension for those configurations lies in some basin that is considered fatal. The computation turns out to require only a relatively small prefix of the unfolding, just twice the depth of Esparza's complete prefix.

cs.FL↗

arXiv2022

Variable-Depth Simulation of Most Permissive Boolean Networks

In systems biology, Boolean networks (BNs) aim at modeling the qualitative dynamics of quantitative biological systems. Contrary to their (a)synchronous interpretations, the Most Permissive (MP) interpretation guarantees capturing all the trajectories of any quantitative system compatible with the BN, without additional parameters. Notably, the MP mode has the ability to capture transitions related to the heterogeneity of time scales and concentration scales in the abstracted quantitative system and which are not captured by asynchronous modes. So far, the analysis of MPBNs has focused on Boolean dynamical properties, such as the existence of particular trajectories or attractors. This paper addresses the sampling of trajectories from MPBNs in order to quantify the propensities of attractors reachable from a given initial BN configuration. The computation of MP transitions from a configuration is performed by iteratively discovering possible state changes. The number of iterations is referred to as the permissive depth, where the first depth corresponds to the asynchronous transitions. This permissive depth reflects the potential concentration and time scales heterogeneity along the abstracted quantitative process. The simulation of MPBNs is illustrated on several models from the literature, on which the depth parametrization can help to assess the robustness of predictions on attractor propensities changes triggered by model perturbations.

eess.SY↗

arXiv2022

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line, and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML, and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.

q-bio.QM↗

arXiv2021

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.

math.DS↗

arXiv2020

SAT Heritage: a community-driven effort for archiving, building and running more than thousand SAT solvers

SAT research has a long history of source code and binary releases, thanks to competitions organized every year. However, since every cycle of competitions has its own set of rules and an adhoc way of publishing source code and binaries, compiling or even running any solver may be harder than what it seems. Moreover, there has been more than a thousand solvers published so far, some of them released in the early 90's. If the SAT community wants to archive and be able to keep track of all the solvers that made its history, it urgently needs to deploy an important effort. We propose to initiate a community-driven effort to archive and to allow easy compilation and running of all SAT solvers that have been released so far. We rely on the best tools for archiving and building binaries (thanks to Docker, GitHub and Zenodo) and provide a consistent and easy way for this. Thanks to our tool, building (or running) a solver from its source (or from its binary) can be done in one line.

cs.AI↗

arXiv2020

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.

cs.FL↗

arXiv2020

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

Boolean 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.

cs.AI↗

arXiv2019

Concurrency in Boolean networks

Boolean networks (BNs) are widely used to model the qualitative dynamics of biological systems. Besides the logical rules determining the evolution of each component with respect to the state of its regulators, the scheduling of component updates can have a dramatic impact on the predicted behaviours. In this paper, we explore the use of Read (contextual) Petri Nets (RPNs) to study dynamics of BNs from a concurrency theory perspective. After showing bi-directional translations between RPNs and BNs and analogies between results on synchronism sensitivity, we illustrate that usual updating modes for BNs can miss plausible behaviours, i.e., incorrectly conclude on the absence/impossibility of reaching specific configurations. We propose an encoding of BNs capitalizing on the RPN semantics enabling more behaviour than the generalized asynchronous updating mode. The proposed encoding ensures a correct abstraction of any multivalued refinement, as one may expect to achieve when modelling biological systems with no assumption on its time features.

cs.LO↗

arXiv2018

Combining Refinement of Parametric Models with Goal-Oriented Reduction of Dynamics

Parametric models abstract part of the specification of dynamical models by integral parameters. They are for example used in computational systems biology, notably with parametric regulatory networks, which specify the global architecture (interactions) of the networks, while parameterising the precise rules for drawing the possible temporal evolutions of the states of the components. A key challenge is then to identify the discrete parameters corresponding to concrete models with desired dynamical properties. This paper addresses the restriction of the abstract execution of parametric regulatory (discrete) networks by the means of static analysis of reachability properties (goal states). Initially defined at the level of concrete parameterised models, the goal-oriented reduction of dynamics is lifted to parametric networks, and is proven to preserve all the minimal traces to the specified goal states. It results that one can jointly perform the refinement of parametric networks (restriction of domain of parameters) while reducing the necessary transitions to explore and preserving reachability properties of interest.

cs.LO↗