Petri nets for systems and synthetic biology

We give a description of a Petri net-based framework for modelling and analysing biochemical pathways, which uni¯es the qualita- tive, stochastic and continuous paradigms. Each perspective adds its con- tribution to the understanding of the system, thus the three approaches do not compete, but complement each other. We illustrate our approach by applying it to an extended model of the three stage cascade, which forms the core of the ERK signal transduction pathway. Consequently our focus is on transient behaviour analysis. We demonstrate how quali- tative descriptions are abstractions over stochastic or continuous descrip- tions, and show that the stochastic and continuous models approximate each other. Although our framework is based on Petri nets, it can be applied more widely to other formalisms which are used to model and analyse biochemical networks

Algorithmic Verification of Asynchronous Programs

Asynchronous programming is a ubiquitous systems programming idiom to manage concurrent interactions with the environment. In this style, instead of waiting for time-consuming operations to complete, the programmer makes a non-blocking call to the operation and posts a callback task to a task buffer that is executed later when the time-consuming operation completes. A co-operative scheduler mediates the interaction by picking and executing callback tasks from the task buffer to completion (and these callbacks can post further callbacks to be executed later). Writing correct asynchronous programs is hard because the use of callbacks, while efficient, obscures program control flow. We provide a formal model underlying asynchronous programs and study verification problems for this model. We show that the safety verification problem for finite-data asynchronous programs is expspace-complete. We show that liveness verification for finite-data asynchronous programs is decidable and polynomial-time equivalent to Petri Net reachability. Decidability is not obvious, since even if the data is finite-state, asynchronous programs constitute infinite-state transition systems: both the program stack and the task buffer of pending asynchronous calls can be potentially unbounded. Our main technical construction is a polynomial-time semantics-preserving reduction from asynchronous programs to Petri Nets and conversely. The reduction allows the use of algorithmic techniques on Petri Nets to the verification of asynchronous programs. We also study several extensions to the basic models of asynchronous programs that are inspired by additional capabilities provided by implementations of asynchronous libraries, and classify the decidability and undecidability of verification questions on these extensions.Comment: 46 pages, 9 figure

Bounded LTL Model Checking with Stable Models

In this paper bounded model checking of asynchronous concurrent systems is introduced as a promising application area for answer set programming. As the model of asynchronous systems a generalisation of communicating automata, 1-safe Petri nets, are used. It is shown how a 1-safe Petri net and a requirement on the behaviour of the net can be translated into a logic program such that the bounded model checking problem for the net can be solved by computing stable models of the corresponding program. The use of the stable model semantics leads to compact encodings of bounded reachability and deadlock detection tasks as well as the more general problem of bounded model checking of linear temporal logic. Correctness proofs of the devised translations are given, and some experimental results using the translation and the Smodels system are presented.Comment: 32 pages, to appear in Theory and Practice of Logic Programmin

Abstracting Asynchronous Multi-Valued Networks: An Initial Investigation

Multi-valued networks provide a simple yet expressive qualitative state based modelling approach for biological systems. In this paper we develop an abstraction theory for asynchronous multi-valued network models that allows the state space of a model to be reduced while preserving key properties of the model. The abstraction theory therefore provides a mechanism for coping with the state space explosion problem and supports the analysis and comparison of multi-valued networks. We take as our starting point the abstraction theory for synchronous multi-valued networks which is based on the finite set of traces that represent the behaviour of such a model. The problem with extending this approach to the asynchronous case is that we can now have an infinite set of traces associated with a model making a simple trace inclusion test infeasible. To address this we develop a decision procedure for checking asynchronous abstractions based on using the finite state graph of an asynchronous multi-valued network to reason about its trace semantics. We illustrate the abstraction techniques developed by considering a detailed case study based on a multi-valued network model of the regulation of tryptophan biosynthesis in Escherichia coli.Comment: Presented at MeCBIC 201

Multiplicative-Additive Proof Equivalence is Logspace-complete, via Binary Decision Trees

Given a logic presented in a sequent calculus, a natural question is that of equivalence of proofs: to determine whether two given proofs are equated by any denotational semantics, ie any categorical interpretation of the logic compatible with its cut-elimination procedure. This notion can usually be captured syntactically by a set of rule permutations. Very generally, proofnets can be defined as combinatorial objects which provide canonical representatives of equivalence classes of proofs. In particular, the existence of proof nets for a logic provides a solution to the equivalence problem of this logic. In certain fragments of linear logic, it is possible to give a notion of proofnet with good computational properties, making it a suitable representation of proofs for studying the cut-elimination procedure, among other things. It has recently been proved that there cannot be such a notion of proofnets for the multiplicative (with units) fragment of linear logic, due to the equivalence problem for this logic being Pspace-complete. We investigate the multiplicative-additive (without unit) fragment of linear logic and show it is closely related to binary decision trees: we build a representation of proofs based on binary decision trees, reducing proof equivalence to decision tree equivalence, and give a converse encoding of binary decision trees as proofs. We get as our main result that the complexity of the proof equivalence problem of the studied fragment is Logspace-complete.Comment: arXiv admin note: text overlap with arXiv:1502.0199

SPDL Model Checking via Property-Driven State Space Generation

In this report we describe how both, memory and time requirements for stochastic model checking of SPDL (stochastic propositional dynamic logic) formulae can significantly be reduced. SPDL is the stochastic extension of the multi-modal program logic PDL.\ud SPDL provides means to specify path-based properties with or without timing restrictions. Paths can be characterised by so-called programs, essentially regular expressions, where the executability can be made dependent on the validity of test formulae. For model-checking SPDL path formulae it is necessary to build a product transition system (PTS)\ud between the system model and the program automaton belonging to the path formula that is to be verified.\ud In many cases, this PTS can be drastically reduced during the model checking procedure, as the program restricts the number of potentially satisfying paths. Therefore, we propose an approach that directly generates the reduced PTS from a given SPA specification and an SPDL path formula.\ud The feasibility of this approach is shown through a selection of case studies, which show enormous state space reductions, at no increase in generation time.\u

From types to type requirements: Genericity for model-driven engineering

The final publication is available at Springer via http://dx.doi.org/10.1007/s10270-011-0221-0Model-driven engineering (MDE) is a software engineering paradigm that proposes an active use of models during the development process. This paradigm is inherently type-centric, in the sense that models and their manipulation are defined over the types of specific meta-models. This fact hinders the reuse of existing MDE artefacts with other meta-models in new contexts, even if all these meta-models share common characteristics. To increase the reuse opportunities of MDE artefacts, we propose a paradigm shift from type-centric to requirement-centric specifications by bringing genericity into models, meta-models and model management operations. For this purpose, we introduce so-called concepts gathering structural and behavioural requirements for models and meta-models. In this way, model management operations are defined over concepts, enabling the application of the operations to any meta-model satisfying the requirements imposed by the concept. Model templates rely on concepts to define suitable interfaces, hence enabling the definition of reusable model components. Finally, similar to mixin layers, templates can be defined at the meta-model level as well, to define languages in a modular way, as well as layers of functionality to be plugged-in into other meta-models. These ideas have been implemented in MetaDepth, a multi-level meta-modelling tool that integrates action languages from the Epsilon family for model management and code generation.This work has been sponsored by the Spanish Ministry of Science and Innovation with projects METEORIC (TIN2008-02081) and Go Lite (TIN2011-24139), and by the R&D program of the Community of Madrid with project “e-Madrid” (S2009/TIC-1650)