Dagstuhl Seminar Proceedings, Volume 9091



Publication Details

  • published at: 2009-05-05
  • Publisher: Schloss Dagstuhl – Leibniz-Zentrum für Informatik

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Document
09091 Abstracts Collection – Formal Methods in Molecular Biology

Authors: Rainer Breitling, David Roger Gilbert, Monika Heiner, and Corrado Priami


Abstract
From 23. February to 27. February 2009, the Dagstuhl Seminar 09091 ``Formal Methods in Molecular Biology '' was held in Schloss Dagstuhl~--~Leibniz Center for Informatics. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available.

Cite as

Rainer Breitling, David Roger Gilbert, Monika Heiner, and Corrado Priami. 09091 Abstracts Collection – Formal Methods in Molecular Biology. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, pp. 1-24, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{breitling_et_al:DagSemProc.09091.1,
  author =	{Breitling, Rainer and Gilbert, David Roger and Heiner, Monika and Priami, Corrado},
  title =	{{09091 Abstracts Collection – Formal Methods in Molecular Biology }},
  booktitle =	{Formal Methods in Molecular Biology},
  pages =	{1--24},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.1},
  URN =		{urn:nbn:de:0030-drops-19972},
  doi =		{10.4230/DagSemProc.09091.1},
  annote =	{Keywords: Formal models, systems biology, biological processes}
}
Document
09091 Executive Summary – Formal Methods in Molecular Biology

Authors: Rainer Breitling, David Roger Gilbert, Monika Heiner, and Corrado Priami


Abstract
Formal logical models play an increasing role in the newly emerging field of Systems Biology. Compared to the classical, well-established approach of modeling biological processes using continuous and stochastic differential equations, formal logical models offer a number of important advantages. Many different formal modeling paradigms have been applied to molecular biology, each with its own community, formalisms and tools. In this seminar we brought together modelers from various backgrounds to stimulate closer interaction within the field and to create a common platform for discussion. A central feature of the seminar was a modeling competition (with a highly collaborative flavor) of various modeling paradigms.

Cite as

Rainer Breitling, David Roger Gilbert, Monika Heiner, and Corrado Priami. 09091 Executive Summary – Formal Methods in Molecular Biology. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{breitling_et_al:DagSemProc.09091.2,
  author =	{Breitling, Rainer and Gilbert, David Roger and Heiner, Monika and Priami, Corrado},
  title =	{{09091 Executive Summary – Formal Methods in Molecular Biology}},
  booktitle =	{Formal Methods in Molecular Biology},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.2},
  URN =		{urn:nbn:de:0030-drops-19964},
  doi =		{10.4230/DagSemProc.09091.2},
  annote =	{Keywords: Formal models, systems biology, biological processes.}
}
Document
Analyzing various models of Circadian Clock and Cell Cycle coupling

Authors: Attila Csikász-Nagy, Adrien Faure, Roberto Larcher, Paola Lecca, Ivan Mura, Ferenc Jordan, Alida Palmisano, Alessandro Romanel, Sean Sedwards, Heike Siebert, Sylvain Soliman, Denis Thieffry, Judit Zámborszky, Tommaso Mazza, and Paolo Ballarini


Abstract
The daily rhythm can influence the proliferation rate of many cell types. In the mammalian system the transcription of the cell cycle regulatory protein Wee1 is controlled by the circadian clock. Zamborszky et al. (2007) present a computational model coupling the cell cycle and circadian rhythm, showing that this coupling can lead to multimodal cell cycle time distributions. Biological data points to additional couplings, including a link back from the cell cycle to the circadian clock. Proper modelling of this coupling requires a more detailed description of both parts of the model. Hence, we aim at further extending and analysing earlier models using a combination of modelling techniques and computer software, including CoSBI lab, BIOCHAM, and GINsim.

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Attila Csikász-Nagy, Adrien Faure, Roberto Larcher, Paola Lecca, Ivan Mura, Ferenc Jordan, Alida Palmisano, Alessandro Romanel, Sean Sedwards, Heike Siebert, Sylvain Soliman, Denis Thieffry, Judit Zámborszky, Tommaso Mazza, and Paolo Ballarini. Analyzing various models of Circadian Clock and Cell Cycle coupling. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, pp. 1-6, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{csikasznagy_et_al:DagSemProc.09091.3,
  author =	{Csik\'{a}sz-Nagy, Attila and Faure, Adrien and Larcher, Roberto and Lecca, Paola and Mura, Ivan and Jordan, Ferenc and Palmisano, Alida and Romanel, Alessandro and Sedwards, Sean and Siebert, Heike and Soliman, Sylvain and Thieffry, Denis and Z\'{a}mborszky, Judit and Mazza, Tommaso and Ballarini, Paolo},
  title =	{{Analyzing various models of Circadian Clock and Cell Cycle coupling}},
  booktitle =	{Formal Methods in Molecular Biology},
  pages =	{1--6},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.3},
  URN =		{urn:nbn:de:0030-drops-19944},
  doi =		{10.4230/DagSemProc.09091.3},
  annote =	{Keywords: Cell cycle, circadian clock, computational modelling}
}
Document
BioModel Engineering: Its role in Systems Biology and Synthetic Biology

Authors: David Roger Gilbert, Rainer Breitling, and Monika Heiner


Abstract
BioModel Engineering takes place at the interface of computing science, mathematics, engineering and biology, and provides a systematic approach for designing, constructing and analyzing computational models of biological systems. Some of its central concepts are inspired by efficient software engineering strategies. BioModel Engineering does not aim at engineering biological systems per se, but rather aims at describing their structure and behavior, in particular at the level of intracellular molecular processes, using computational tools and techniques in a principled way. The two major application areas of BioModel Engineering are systems biology and synthetic biology. In the former, the aim is the design and construction of models of existing biological systems, which explain observed properties and predict the response to experimental interventions; in the latter, BioModel Engineering is used as part of a general strategy for designing and constructing synthetic biological systems with novel functionalities. The overall steps in building computational models in a BioModel Engineering framework are: Problem Identification, Model Construction, Static and Dynamic Analysis, Simulation, and Model management and development. A major theme in BioModel Engineering is that of constructing a (qualitative) model means (1) finding the structure, (2) obtaining an initial state and (3) parameter fitting. In an approach that we have taken, the structure is obtained by piecewise construction of models from modular parts, the initial state which describes concentrations of species or numbers of molecules is obtained by analysis of the structure, and parameter fitting comprises determining the rate parameters of the kinetic equations by reference to trusted data. Model checking can play a key role in BioModel Engineering – for example in recent work we have shown how parameter estimation can be achieved by characterising the desired behaviour of a model with a temporal logic property and altering the model to make it conform to the property as determined through model checking.

Cite as

David Roger Gilbert, Rainer Breitling, and Monika Heiner. BioModel Engineering: Its role in Systems Biology and Synthetic Biology. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, pp. 1-2, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{gilbert_et_al:DagSemProc.09091.4,
  author =	{Gilbert, David Roger and Breitling, Rainer and Heiner, Monika},
  title =	{{BioModel Engineering: Its role in Systems Biology and Synthetic Biology}},
  booktitle =	{Formal Methods in Molecular Biology},
  pages =	{1--2},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.4},
  URN =		{urn:nbn:de:0030-drops-19929},
  doi =		{10.4230/DagSemProc.09091.4},
  annote =	{Keywords: Biochemical systems, models, design, construction, systems biology, synthetic biology, model checking.}
}
Document
Modelling and analysis of the NF-$kappa$B pathway in Bio-PEPA

Authors: Federica Ciocchetta, Andrea Degasperi, John Heath, and Jane Hillston


Abstract
In this work we present a Bio-PEPA model describing the Nuclear Factor $kappa$B (NF-$kappa$B) signalling pathway. In particular our model focuses on the dynamic response of NF-$kappa$B to an external stimulus. Each biochemical species in the pathway is represented by a specific Bio-PEPA component and the external stimulus is abstracted by Bio-PEPA events. The Bio-PEPA model is a formal intermediate representation of the pathway on which various kinds of analysis can be performed. Both stochastic and deterministic simulations are carried out to validate our model against the experimental data in the literature and to verify some properties, such as the impact of the stimulus duration and of the NF-$kappa$B initial amount on the behaviour of some species. Finally, sensitivity analysis is considered to investigate the most influential parameters of the model.

Cite as

Federica Ciocchetta, Andrea Degasperi, John Heath, and Jane Hillston. Modelling and analysis of the NF-$kappa$B pathway in Bio-PEPA. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, pp. 1-18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{ciocchetta_et_al:DagSemProc.09091.5,
  author =	{Ciocchetta, Federica and Degasperi, Andrea and Heath, John and Hillston, Jane},
  title =	{{Modelling and analysis of the NF-\$kappa\$B pathway in Bio-PEPA}},
  booktitle =	{Formal Methods in Molecular Biology},
  pages =	{1--18},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.5},
  URN =		{urn:nbn:de:0030-drops-19911},
  doi =		{10.4230/DagSemProc.09091.5},
  annote =	{Keywords: Process algebras, NF-\$kappa\$B pathway, modelling, analysis}
}
Document
Rule-based Modeling of Transcriptional Attenuation at the Tryptophan Operon

Authors: Céline Kuttler, Cédric Lhoussaine, and Mirabelle Nebut


Abstract
Transcriptional attenuation at E.coli's tryptophan operon is a prime example of RNA-mediated gene regulation. In this paper, we present a discrete stochastic model for this phenomenon based on chemical reactions. Our model is compact and intelligible, due to n-ary reactions (which preclude object-centric approaches) and to rule schemas that define finite sets of chemical reactions. Stochastic simulations with our model confirm results that were previously obtained by master equations or differential equations. In addition, our approach permits to reflect mutation experiments by simple model modifications, and to re-use model components for transcriptional attenuation in other genes and organisms.

Cite as

Céline Kuttler, Cédric Lhoussaine, and Mirabelle Nebut. Rule-based Modeling of Transcriptional Attenuation at the Tryptophan Operon. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, pp. 1-22, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{kuttler_et_al:DagSemProc.09091.6,
  author =	{Kuttler, C\'{e}line and Lhoussaine, C\'{e}dric and Nebut, Mirabelle},
  title =	{{Rule-based Modeling of Transcriptional Attenuation at the Tryptophan Operon}},
  booktitle =	{Formal Methods in Molecular Biology},
  pages =	{1--22},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.6},
  URN =		{urn:nbn:de:0030-drops-19938},
  doi =		{10.4230/DagSemProc.09091.6},
  annote =	{Keywords: Systems biology, rule-based modeling languages, stochastic simulation, kappa.}
}
Document
Stochastic modelling of cellular growth and division by means of the pi@ calculus

Authors: Cristian Versari


Abstract
The application of Concurrency Theory to Systems Biology is in its earliest stage of progress. The metaphor of cells as computing systems by Regev and Shapiro opened the employment of concurrent languages for the modelling of biological systems. Their peculiar characteristics led to the design of many bio-inspired formalisms which achieve higher faithfulness and specificity. In this paper we discuss the application to the biological modelling of pi@, a core calculus for the representation of biological systems. The pi@ language represents a keystone in this respect, thanks to its expressiveness capabilities which allow the modelling of a wide variety of phenomena (e.g. simple chemical reactions, but also formation of molecular or protein complexes, organisation of complex system in dynamical compartment hierarchies) despite of its simplicity and conservativeness. Here we analyse a biological case study involving cellular growth and division, modelled in the stochastic variant of pi@: the case study is formalised and stochastically simulated according to a multi-compartment extension of Gillespie's stochastic simulation algorithm. The results underline the usefulness of the modelling approach adopted in pi@ for the correct handling of systems with variable volume.

Cite as

Cristian Versari. Stochastic modelling of cellular growth and division by means of the pi@ calculus. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, pp. 1-15, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{versari:DagSemProc.09091.7,
  author =	{Versari, Cristian},
  title =	{{Stochastic modelling of cellular growth and division by means of the pi@ calculus}},
  booktitle =	{Formal Methods in Molecular Biology},
  pages =	{1--15},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.7},
  URN =		{urn:nbn:de:0030-drops-19907},
  doi =		{10.4230/DagSemProc.09091.7},
  annote =	{Keywords: Process algebra, pi-calculus, simulation, stochastic}
}
Document
Symbolic Steady States and Dynamically Essential Subnetworks of Discrete Regulatory Networks

Authors: Heike Siebert


Abstract
Analyzing complex networks is a difficult task, regardless of the chosen modeling framework. For a discrete regulatory network, even if the number of components is in some sense manageable, we have to deal with the problem of analyzing the dynamics in an exponentially large state space. A well known idea to approach this difficulty is to identify smaller building blocks of the system the study of which in isolation still renders information on the dynamics of the whole network. In this talk, we introduce the notion of symbolic steady state which allows us to identify such building blocks. We state explicit rules how to derive attractors of the network from subnetwork attractors valid for synchronous as well as asynchronous dynamics. Illustrating those rules, we derive general conditions for circuits embedded in the network to transfer their behavioral characteristics pertaining number and size of attractors observed in isolation to the complex network.

Cite as

Heike Siebert. Symbolic Steady States and Dynamically Essential Subnetworks of Discrete Regulatory Networks. In Formal Methods in Molecular Biology. Dagstuhl Seminar Proceedings, Volume 9091, pp. 1-3, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2009)


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@InProceedings{siebert:DagSemProc.09091.8,
  author =	{Siebert, Heike},
  title =	{{Symbolic Steady  States and Dynamically Essential Subnetworks of Discrete Regulatory Networks}},
  booktitle =	{Formal Methods in Molecular Biology},
  pages =	{1--3},
  series =	{Dagstuhl Seminar Proceedings (DagSemProc)},
  ISSN =	{1862-4405},
  year =	{2009},
  volume =	{9091},
  editor =	{Rainer Breitling and David Roger Gilbert and Monika Heiner and Corrado Priami},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/DagSemProc.09091.8},
  URN =		{urn:nbn:de:0030-drops-19957},
  doi =		{10.4230/DagSemProc.09091.8},
  annote =	{Keywords: Discrete networks, logical analysis, symbolic steady states}
}

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