Towards modular verification of pathways: fairness and assumptions

Modular verification is a technique used to face the state explosion problem often encountered in the verification of properties of complex systems such as concurrent interactive systems. The modular approach is based on the observation that properties of interest often concern a rather small portion of the system. As a consequence, reduced models can be constructed which approximate the overall system behaviour thus allowing more efficient verification. Biochemical pathways can be seen as complex concurrent interactive systems. Consequently, verification of their properties is often computationally very expensive and could take advantage of the modular approach. In this paper we report preliminary results on the development of a modular verification framework for biochemical pathways. We view biochemical pathways as concurrent systems of reactions competing for molecular resources. A modular verification technique could be based on reduced models containing only reactions involving molecular resources of interest. For a proper description of the system behaviour we argue that it is essential to consider a suitable notion of fairness, which is a well-established notion in concurrency theory but novel in the field of pathway modelling. We propose a modelling approach that includes fairness and we identify the assumptions under which verification of properties can be done in a modular way. We prove the correctness of the approach and demonstrate it on the model of the EGF receptor-induced MAP kinase cascade by Schoeberl et al.Comment: In Proceedings MeCBIC 2012, arXiv:1211.347

Modular Verification of Biological Systems

Systems of interest in systems biology (such as metabolic pathways, signalling pathways and gene regulatory networks) often consist of a huge number of components interacting in different ways, thus exhibiting very complex behaviours. In biology, such behaviours are usually explored by means of simulation techniques applied to models defined on the basis of system observation and of hypotheses on its functioning. Model checking has also been recently applied to the analysis of biological systems. This analysis technique typically relies on a state space representation whose size, unfortunately, makes the analysis often intractable for realistic models. A method for trying to avoid the state space explosion problem is to consider a decomposition of the system, and to apply a modular verification technique. In particular, properties to be verified often concern only a small portion of the modelled system rather than the system as a whole. Hence, for each property it would be useful to be able to isolate a minimal fragment of the model that is necessary to verify such a property. In this thesis we introduce a modular verification technique in which the system of interest is described by means of an automata-based formalism, called sync-programs, that supports modular construction. Our modular verification technique is based on results of Grumberg et al.~and on their application to the theory of concurrent systems proposed by Attie and Emerson. In particular, we adapt Attie and Emerson's approach to deal with biological systems by allowing automata to synchronise by performing transitions simultaneously. Modular verification allows qualitative aspects of systems to be analysed with the guarantee that properties proved to hold in a suitable model fragment also hold in the whole model. The correctness of the verification technique is proved. The class of properties preserved is ACTL$^{-}$, the universal fragment of temporal logic CTL. The preservation holds only for positive answers and negative answers are not necessarily preserved. In order to verify properties we use the NuSMV model checker, which is a well-established and efficient instrument. We provide a formal translation of sync-programs to simpler automata, which can be given as input to NuSMV. We prove the correspondence of the verification problems. We show the application of our verification technique in some biological case studies. We compare the time required to verify the property on the whole model with the time needed to verify the same property by only considering those modules which are involved in the behaviour of the system related to the property. In order to handle modelling and verification of more realistic biological scenarios, we propose also a dynamic version of our formalism. It allows entities to be created dynamically, in particular by other already running entities, as it often happens in biological systems. Moreover, multiple copies of the same entities can be present at the same time in a system. We show a correspondence of our model with Petri Nets. This has a consequence that tools developed for Petri Nets could be used also for dynamic sync-programs. Modular verification allows properties expressed as DACTL- formulae (dynamic version of ACTL-) to be verified on a portion of the model. The results of analysis of the case study of the MAP kinase cascade activated by surface and internalised EGF receptors, which consists of 143 species and 80 reactions, suggest applicability and scalability of the approach. The results raise the prospect of rendering tractable problems that are currently intractable in the verification of biological systems. In addition, we expect that the techniques developed in the thesis could be applied with profit not only to models of biological systems, but more generally to models of concurrent systems

A service-oriented architecture for integrating the modeling and formal verification of genetic regulatory networks

<p>Abstract</p> <p>Background</p> <p>The study of biological networks has led to the development of increasingly large and detailed models. Computer tools are essential for the simulation of the dynamical behavior of the networks from the model. However, as the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in a large number of simulation traces. Formal verification based on temporal logic and model checking provides promising methods to automate and scale the analysis of the models. However, a framework that tightly integrates modeling and simulation tools with model checkers is currently missing, on both the conceptual and the implementational level.</p> <p>Results</p> <p>We have developed a generic and modular web service, based on a service-oriented architecture, for integrating the modeling and formal verification of genetic regulatory networks. The architecture has been implemented in the context of the qualitative modeling and simulation tool G<smcaps>NA</smcaps> and the model checkers N<smcaps>U</smcaps>SMV and C<smcaps>ADP</smcaps>. G<smcaps>NA</smcaps> has been extended with a verification module for the specification and checking of biological properties. The verification module also allows the display and visual inspection of the verification results.</p> <p>Conclusions</p> <p>The practical use of the proposed web service is illustrated by means of a scenario involving the analysis of a qualitative model of the carbon starvation response in <it>E. coli</it>. The service-oriented architecture allows modelers to define the model and proceed with the specification and formal verification of the biological properties by means of a unified graphical user interface. This guarantees a transparent access to formal verification technology for modelers of genetic regulatory networks.</p

A review of modelling and verification approaches for computational biology

This paper reviews most frequently used computational modelling approaches and formal verification techniques in computational biology. The paper also compares a number of model checking tools and software suits used in analysing biological systems and biochemical networks and verifiying a wide range of biological properties

Conceptual System Dynamics and Agent-Based Modelling Simulation of Interorganisational Fairness in Food Value Chains: Research Agenda and Case Studies

open16siThe research on which this paper is based formed part of the VALUMICS project “Understanding Food Value Chain and Network Dynamics” funded from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 727243System dynamics and agent-based simulation modelling approaches have a potential as tools to evaluate the impact of policy related decision making in food value chains. The context is that a food value chain involves flows of multiple products, financial flows and decision making among the food value chain players. Each decision may be viewed from the level of independent actors, each with their own motivations and agenda, but responding to externalities and to the behaviours of other actors. The focus is to show how simulation modelling can be applied to problems such as fairness and power asymmetries in European food value chains by evaluating the outcome of interventions in terms of relevant operational indicators of interorganisational fairness (e.g., profit distribution, market power, bargaining power). The main concepts of system dynamics and agent-based modelling are introduced and the applicability of a hybrid of these methods to food value chains is justified. This approach is outlined as a research agenda, and it is demonstrated how cognitive maps can help in the initial conceptual model building when implemented for specific food value chains studied in the EU Horizon 2020 VALUMICS project. The French wheat to bread chain has many characteristics of food value chains in general and is applied as an example to formulate a model that can be extended to capture the functioning of European FVCs. This work is to be further progressed in a subsequent stream of research for the other food value chain case studies with different governance modes and market organisation, in particular, farmed salmon to fillet, dairy cows to milk and raw tomato to processed tomato.openMcGarraghy S.; Olafsdottir G.; Kazakov R.; Huber E.; Loveluck W.; Gudbrandsdottir I.Y.; Cechura L.; Esposito G.; Samoggia A.; Aubert P.-M.; Barling D.; Duric I.; Jaghdani T.J.; Thakur M.; Saviolidis N.M.; Bogason S.G.McGarraghy S.; Olafsdottir G.; Kazakov R.; Huber E.; Loveluck W.; Gudbrandsdottir I.Y.; Cechura L.; Esposito G.; Samoggia A.; Aubert P.-M.; Barling D.; Duric I.; Jaghdani T.J.; Thakur M.; Saviolidis N.M.; Bogason S.G

Conceptual System Dynamics and Agent-Based Modelling Simulation of Interorganisational Fairness in Food Value Chains: Research Agenda and Case Studies

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)System dynamics and agent-based simulation modelling approaches have a potential as tools to evaluate the impact of policy related decision making in food value chains. The context is that a food value chain involves flows of multiple products, financial flows and decision making among the food value chain players. Each decision may be viewed from the level of independent actors, each with their own motivations and agenda, but responding to externalities and to the behaviours of other actors. The focus is to show how simulation modelling can be applied to problems such as fairness and power asymmetries in European food value chains by evaluating the outcome of interventions in terms of relevant operational indicators of interorganisational fairness (e.g., profit distribution, market power, bargaining power). The main concepts of system dynamics and agent-based modelling are introduced and the applicability of a hybrid of these methods to food value chains is justified. This approach is outlined as a research agenda, and it is demonstrated how cognitive maps can help in the initial conceptual model building when implemented for specific food value chains studied in the EU Horizon 2020 VALUMICS project. The French wheat to bread chain has many characteristics of food value chains in general and is applied as an example to formulate a model that can be extended to capture the functioning of European FVCs. This work is to be further progressed in a subsequent stream of research for the other food value chain case studies with different governance modes and market organisation, in particular, farmed salmon to fillet, dairy cows to milk and raw tomato to processed tomato.Peer reviewedFinal Published versio

Taming the Big Green Elephant

In this open access publication it is shown, that sustainable low carbon development is a transformative process that constitutes the shifting from the initially chosen or taken pathway to another pathway as goals have been re-visited and revised to enable the system to adapt to changes. However, shifting entails transition costs that are accrued through the effects of lock-ins that have framed decisions and collective actions. The uncertainty about these costs can be overwhelming or even disruptive. This book aims to provide a comprehensive and integrated analytical framework that promotes the understanding of transformation towards sustainability. The analysis of this book is built upon negotiative perspectives to help define, design, and facilitate collective actions in order to execute the principles of sustainability

Taming the Big Green Elephant

In this open access publication it is shown, that sustainable low carbon development is a transformative process that constitutes the shifting from the initially chosen or taken pathway to another pathway as goals have been re-visited and revised to enable the system to adapt to changes. However, shifting entails transition costs that are accrued through the effects of lock-ins that have framed decisions and collective actions. The uncertainty about these costs can be overwhelming or even disruptive. This book aims to provide a comprehensive and integrated analytical framework that promotes the understanding of transformation towards sustainability. The analysis of this book is built upon negotiative perspectives to help define, design, and facilitate collective actions in order to execute the principles of sustainability

A framework for characterising and evaluating the effectiveness of environmental modelling

Environmental modelling is transitioning from the traditional paradigm that focuses on the model and its quantitative performance to a more holistic paradigm that recognises successful model-based outcomes are closely tied to undertaking modelling as a social process, not just as a technical procedure. This paper redefines evaluation as a multi-dimensional and multi-perspective concept, and proposes a more complete framework for identifying and measuring the effectiveness of modelling that serves the new paradigm. Under this framework, evaluation considers a broader set of success criteria, and emphasises the importance of contextual factors in determining the relevance and outcome of the criteria. These evaluation criteria are grouped into eight categories: project efficiency, model accessibility, credibility, saliency, legitimacy, satisfaction, application, and impact. Evaluation should be part of an iterative and adaptive process that attempts to improve model-based outcomes and foster pathways to better futures