An Abstraction Theory for Qualitative Models of Biological Systems

Multi-valued network models are an important qualitative modelling approach used widely by the biological community. In this paper we consider developing an abstraction theory for multi-valued network models that allows the state space of a model to be reduced while preserving key properties of the model. This is important as it aids the analysis and comparison of multi-valued networks and in particular, helps address the well-known problem of state space explosion associated with such analysis. We also consider developing techniques for efficiently identifying abstractions and so provide a basis for the automation of this task. We illustrate the theory and techniques developed by investigating the identification of abstractions for two published MVN models of the lysis-lysogeny switch in the bacteriophage lambda.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

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

Abstracting Asynchronous Multi-Valued Networks

Multi-valued networks (MVNs) provide a simple yet expressive qualitative state based modelling approach for biological systems. In this paper we develop an abstraction theory for asynchronous MVNs that allows the state space of a model to be reduced while preserving key properties. The abstraction theory therefore provides a mechanism for coping with the state space explosion problem and supports the analysis and comparison of MVNs. We take as our starting point the abstraction theory for synchronous MVNs which uses the under- approximation approach of trace set inclusion. We show this definition of asynchronous abstraction allows the sound inference of analysis properties and preserves other interesting model properties. One problem that arises in the asynchronous case is that the trace set of an MVN can be infinite making a simple trace set inclusion check infeasible. To address this we develop a decision procedure for checking asynchronous abstractions based on using the finite state graph of an asynchronous MVN to reason about its trace semantics and formally show that this decision procedure is correct. We illustrate the abstraction techniques developed by considering two detailed case studies in which asynchronous abstractions are identified and validated for existing asynchronous MVN models taken from the literature

Integrating heterogeneous knowledges for understanding biological behaviors: a probabilistic approach

Despite recent molecular technique improvements, biological knowledge remains incomplete. Reasoning on living systems hence implies to integrate heterogeneous and partial informations. Although current investigations successfully focus on qualitative behaviors of macromolecular networks, others approaches show partial quantitative informations like protein concentration variations over times. We consider that both informations, qualitative and quantitative, have to be combined into a modeling method to provide a better understanding of the biological system. We propose here such a method using a probabilistic-like approach. After its exhaustive description, we illustrate its advantages by modeling the carbon starvation response in Escherichia coli. In this purpose, we build an original qualitative model based on available observations. After the formal verification of its qualitative properties, the probabilistic model shows quantitative results corresponding to biological expectations which confirm the interest of our probabilistic approach.Comment: 10 page

Towards Autopoietic Computing

A key challenge in modern computing is to develop systems that address complex, dynamic problems in a scalable and efficient way, because the increasing complexity of software makes designing and maintaining efficient and flexible systems increasingly difficult. Biological systems are thought to possess robust, scalable processing paradigms that can automatically manage complex, dynamic problem spaces, possessing several properties that may be useful in computer systems. The biological properties of self-organisation, self-replication, self-management, and scalability are addressed in an interesting way by autopoiesis, a descriptive theory of the cell founded on the concept of a system's circular organisation to define its boundary with its environment. In this paper, therefore, we review the main concepts of autopoiesis and then discuss how they could be related to fundamental concepts and theories of computation. The paper is conceptual in nature and the emphasis is on the review of other people's work in this area as part of a longer-term strategy to develop a formal theory of autopoietic computing.Comment: 10 Pages, 3 figure

Process Calculi Abstractions for Biology

Several approaches have been proposed to model biological systems by means of the formal techniques and tools available in computer science. To mention just a few of them, some representations are inspired by Petri Nets theory, and some other by stochastic processes. A most recent approach consists in interpreting the living entities as terms of process calculi where the behavior of the represented systems can be inferred by applying syntax-driven rules. A comprehensive picture of the state of the art of the process calculi approach to biological modeling is still missing. This paper goes in the direction of providing such a picture by presenting a comparative survey of the process calculi that have been used and proposed to describe the behavior of living entities. This is the preliminary version of a paper that was published in Algorithmic Bioprocesses. The original publication is available at http://www.springer.com/computer/foundations/book/978-3-540-88868-

BioDiVinE: A Framework for Parallel Analysis of Biological Models

In this paper a novel tool BioDiVinEfor parallel analysis of biological models is presented. The tool allows analysis of biological models specified in terms of a set of chemical reactions. Chemical reactions are transformed into a system of multi-affine differential equations. BioDiVinE employs techniques for finite discrete abstraction of the continuous state space. At that level, parallel analysis algorithms based on model checking are provided. In the paper, the key tool features are described and their application is demonstrated by means of a case study

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

Analysis and Synthesis of Metadata Goals for Scientific Data

The proliferation of discipline-specific metadata schemes contributes to artificial barriers that can impede interdisciplinary and transdisciplinary research. The authors considered this problem by examining the domains, objectives, and architectures of nine metadata schemes used to document scientific data in the physical, life, and social sciences. They used a mixed-methods content analysis and Greenberg’s (2005) metadata objectives, principles, domains, and architectural layout (MODAL) framework, and derived 22 metadata-related goals from textual content describing each metadata scheme. Relationships are identified between the domains (e.g., scientific discipline and type of data) and the categories of scheme objectives. For each strong correlation (\u3e0.6), a Fisher’s exact test for nonparametric data was used to determine significance (p \u3c .05). Significant relationships were found between the domains and objectives of the schemes. Schemes describing observational data are more likely to have “scheme harmonization” (compatibility and interoperability with related schemes) as an objective; schemes with the objective “abstraction” (a conceptual model exists separate from the technical implementation) also have the objective “sufficiency” (the scheme defines a minimal amount of information to meet the needs of the community); and schemes with the objective “data publication” do not have the objective “element refinement.” The analysis indicates that many metadata-driven goals expressed by communities are independent of scientific discipline or the type of data, although they are constrained by historical community practices and workflows as well as the technological environment at the time of scheme creation. The analysis reveals 11 fundamental metadata goals for metadata documenting scientific data in support of sharing research data across disciplines and domains. The authors report these results and highlight the need for more metadata-related research, particularly in the context of recent funding agency policy changes