Verification of Spatial and Temporal Modalities in Biochemical Systems

AbstractBiochemical systems such as metabolic and signaling pathways tend to be arranged in a physical space: the product of one reaction must be in the right place to become the reactant for the subsequent reaction in the pathway. Moreover, in some cases, the behavior of the systems can depend on both, the location of the reactants as well as on the time needed for the reaction to occur. We address the problem of specifying and verifying properties of biochemical systems that exhibit both temporal and spatial modalities at the same time. For that, we use as specification language a fragment of intuitionistic linear logic with subexponentials (SELL). The subexponential signature allows us to capture the spatial relations among the different components of the system and the timed constraints for reactions to occur. We show that our framework is general enough to give a declarative semantics to P-Systems and we show that such logical characterization has a strong level of adequacy. Hence, derivations in SELL follow exactly the behavior of the modeled system

Closure Hyperdoctrines

(Pre)closure spaces are a generalization of topological spaces covering also the notion of neighbourhood in discrete structures, widely used to model and reason about spatial aspects of distributed systems. In this paper we present an abstract theoretical framework for the systematic investigation of the logical aspects of closure spaces. To this end, we introduce the notion of closure (hyper)doctrines, i.e. doctrines endowed with inflationary operators (and subject to suitable conditions). The generality and effectiveness of this concept is witnessed by many examples arising naturally from topological spaces, fuzzy sets, algebraic structures, coalgebras, and covering at once also known cases such as Kripke frames and probabilistic frames (i.e., Markov chains). By leveraging general categorical constructions, we provide axiomatisations and sound and complete semantics for various fragments of logics for closure operators. Hence, closure hyperdoctrines are useful both for refining and improving the theory of existing spatial logics, and for the definition of new spatial logics for new applications

Continuous-time temporal logic specification and verification for nonlinear biological systems in uncertain contexts

In this thesis we introduce a complete framework for modelling and verification of biological systems in uncertain contexts based on the bond-calculus process algebra and the LBUC spatio-temporal logic. The bond-calculus is a biological process algebra which captures complex patterns of interaction based on affinity patterns, a novel communication mechanism using pattern matching to express multiway interaction affinities and general kinetic laws, whilst retaining an agent-centric modelling style for biomolecular species. The bond-calculus is equipped with a novel continuous semantics which maps models to systems of Ordinary Differential Equations (ODEs) in a compositional way. We then extend the bond-calculus to handle uncertain models, featuring interval uncertainties in their species concentrations and reaction rate parameters. Our semantics is also extended to handle uncertainty in every aspect of a model, producing non-deterministic continuous systems whose behaviour depends either on time-independent uncertain parameters and initial conditions, corresponding to our partial knowledge of the system at hand, or time-varying uncertain inputs, corresponding to genuine variability in a system’s behaviour based on environmental factors. This language is then coupled with the LBUC spatio-temporal logic which combines Signal Temporal Logic (STL) temporal operators with an uncertain context operator which quantifies over an uncertain context model describing the range of environments over which a property must hold. We develop model-checking procedures for STL and LBUC properties based on verified signal monitoring over flowpipes produced by the Flow* verified integrator, including the technique of masking which directs monitoring for atomic propositions to time regions relevant to the overall verification problem at hand. This allows us to monitor many interesting nested contextual properties and frequently reduces monitoring costs by an order of magnitude. Finally, we explore the technique of contextual signal monitoring which can use a single Flow* flowpipe representing a functional dependency to complete a whole tree of signals corresponding to different uncertain contexts. This allows us to produce refined monitoring results over the whole space and to explore the variation in system behaviour in different contexts

Modal Logics for Brane Calculus

The Brane Calculus is a calculus of mobile processes, intended to model the transport machinery of a cell system. In this paper, we introduce the Brane Logic, a modal logic for expressing formally properties about systems in Brane Calculus. Similarly to previous logics for mobile ambients, Brane Logic has specific spatial and temporal modalities. Moreover, since in Brane Calculus the activity resides on membrane surfaces and not inside membranes, we need to add a specific logic (akin Hennessy-Milner’s) for reasoning about membrane activity.\ud We present also a proof system for deriving valid sequents in Brane Logic. Finally, we present a model checker for a decidable fragment of this logic