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data structures and software dependability

computer science department

brandenburg university of technology cottbus - senftenberg

Scaling up from single molecules to multicellular systems:
modelling over time and space with advanced Petri net techniques


What

Tutorial in two parts, which can be booked separately:

Where

12th International Conference on Systems Biology (ICSB 2011), Heidelberg

When

27/28 August 2011

 

Organizers

Mary Ann Blätke

Otto von Guericke University Magdeburg, Germany
mary-ann.blaetke (at) ovgu.de

David Gilbert

Brunel University, School of Information Systems, Computing and Mathematics, Uxbridge/London, UK
david.gilbert (at) brunel.ac.uk

Monika Heiner

Brandenburg University of Technology at Cottbus, Computer Science Institute, Germany
monika.heiner (at) informatik.tu-cottbus.de

P A R T 1: Saturday, 27 August 2011: 14.30 - 19.00 h (Tutorial 20)

Scaling up from single molecules to multicellular systems:
modelling over time and space with advanced Petri net technique
- Foundations of Advanced Petri Nets -


Abstract:

Petri nets provide an intuitively understandable unifying modeling framework for the accurate graphical representation of molecular or biological mechanisms in conjunction with advanced simulation methodology. Requiring no prior knowlege, this tutorial is equally appealing for wet-lab biologists who are seeking for an easy access to modeling and simulation as well as for dry-lab scientists that use computational methods in their systems biology research. In addition it is of benefit for any audience with a background in computing science and/or model engineering. The presenters' backgrounds cover biosystems engineering, bioinformatics and computer science.

We will revise basic concepts in qualitative Petri nets (structure, behaviour) and their standard analysis techniques, and then go on to introduce quantitative concepts of stochastic and continuous Petri nets within a conceptional framework. The participants will learn to use several standard modelling scenarios, which help in building a library of design patterns.

Next, we will introduce principles of BioModel Engineering with an emphasis on modular modelling, illustrated by a pain signalling network. This modular modelling approach is generalisable to a protein-oriented modelling platform to manage approved curated modules for the generation of molecular networks.

We will demonstrate how the model behaviour can be analysed using analytical and simulative model checking and illustrate further application scenarios of behaviour checking.

All topics will be combined with practical exercises for constructing, modifying, simulating and analysing models. Software (Snoopy, Charlie, Marcie) is freely available for all standard platforms (Mac OS, Windows, Linux/selected distributions) and examples will be provided. Participants can bring their own laptops for the practical exercises or use local computers with the required software installed (depending on availability).

The examples used for illustration will be of increasing complexity which will ultimately demonstrate the need for more advanced techniques. This will be the subject of the second part of this tutorial - "Further Advanced Petri Nets".


Schedule:

  1. Revision of basic qualitative Petri net concepts in the context of biological applications:
    building a library of design patterns;
  2. Introduction into advanced concepts:
    stochastic, continuous, and hybrid Petri nets and related analysis/simulation techniques;
  3. BioModel Engineering via modular, protein-oriented modelling;
  4. Behaviour checking techniques;

All topics will be combined with practical exercises: constructing, modifying, simulating and analysing models at the intracellular level: metabolic and signalling pathways, channels, receptors.

P A R T 2: Sunday, 28 August 2011: 9.00 - 13.30 h (Tutorial 21)

Scaling up from single molecules to multicellular systems:
modelling over time and space with advanced Petri net technique
- Further Advanced Petri Nets -


Abstract:

This second part of the tutorial builds upon understanding the basic Petri net concepts, acquired, e.g. by the first part of this tutorial.

Modelling across multiple scales is a current challenge in systems biology, especially when applied to multicellular organisms. In this tutorial we will discuss advanced approaches to model at different time and spatial scales using hybrid, coloured, and hierarchically coloured Petri nets.

We will illustrate different levels of abstraction that can be used in order to assist the systematic modelling of complex systems involving intra- and inter-cellular signalling mechanisms, and we provide design patterns for similar modelling problems, including repetition and variation of components, organisation of components (topology), communication between components, mobility/motility, and hierarchical organisation of components.

All topics will be combined with practical exercises for constructing, modifying, simulating and analysing models. Software (Snoopy, Charlie, Marcie) is freely available for all standard platforms (Mac OS, Windows, Linux/selected distributions) and examples will be provided. Participants can bring their own laptops for the practical exercises or use local computers with the required software installed (depending on availability).

All topics will be combined with practical exercises: constructing, modifying, simulating and analysing models at the intracellular level: metabolic and signalling pathways, channels, receptors.

The examples used for illustration include: intracellular level - calcium channels and receptors; multiple cells: cell motility and colonial structures; complex organisms: planar cell polarity in tissues (drosophila).


Schedule:

  1. Advanced modelling concepts: coloured, and hierarchically coloured Petri nets;
  2. Challenges in multi-scale modelling for systems biology: from single to multi-cell systems;
  3. Detailed discussion and analysis of examples:
    intracellular level - calcium channels and receptors;
    multiple cells: cell motility and colonial structures;
    complex organisms: planar cell polarity in tissues (drosophila);

All topics will be combined with practical exercises: constructing, modifying, simulating and analysing models.

Tools and Material

Tools


Supplementary Material

Slides

P A R T 1 :

Foundations of Advanced Petri Nets

Introduction into Advanced Concepts

P A R T 2 :

Further Advanced Petri Nets

Detailed discussion and analysis of examples:

Analysis techniques for multiscale models

Wrap-up

  • All:
    Challenges in multi-scale modelling for systems biology: from single to multi-cell systems.

Some References

Beginners might find it helpful to got through the following material in the given order:

  1. W Marwan, C Rohr, M Heiner (2011): Petri nets in Snoopy: A unifying framework for the graphical display, computational modelling, and simulation of bacterial regulatory networks; In Methods in Molecular Biology – Bacterial Molecular Networks, (Jv Helden, A Toussaint and D Thieffry, Eds.), Humana Press, in production.
  2. M Heiner, R Donaldson, D Gilbert (2010): Petri Nets for Systems Biology; In Symbolic Systems Biology: Theory and Methods, (MS Iyengar, Ed.), Jones & Bartlett Learning, LCC, pages 61–97.
  3. M Heiner, D Gilbert, Donaldson (2008), Petri Nets for Systems and Synthetic Biology. In M Bernardo, P Degano, and G Zavattaro (Eds.): SFM 2008, Springer LNCS 5016, pp. 215-264, 2008.

More background papers

  1. M Heiner, D Gilbert (2011): How Might Petri Nets Enhance Your Systems Biology Toolkit; In Proc. PETRI NETS 2011, LNCS 6709, Springer, pages 17–37.
  2. S Soliman, M Heiner: A Unique Transformation from Ordinary Differential Equations to Reaction Networks; PLoS ONE, 5(12):e14284, 2010.
  3. M Heiner, S Lehrack, D Gilbert, W Marwan (2009): Extended Stochastic Petri Nets for Model-based Design of Wetlab Experiments; Transactions on Computational Systems Biology XI, 5750:138–163.
  4. R Breitling, D Gilbert, M Heiner, R Orton (2008). A structured approach for the engineering of biochemical network models, illustrated for signalling pathways. Briefings Bioinformatics September 2008; 9: 404 - 421 [preprint]
  5. D Gilbert, M Heiner, S Lehrack (2007). A Unifying Framework for Modelling and Analysing Biochemical Pathways Using Petri Nets In proceedings CMSB 2007 (Computational Methods in Systems Biology), Editors: M.Calder and S.Gilmore, Springer LNCS/LNBI 4695, pp. 200-216.
  6. D Gilbert, M Heiner, (2006). From Petri Nets to Differential Equations - an Integrative Approach for Biochemical Network Analysis, 27th International Conference on Application and Theory of Petri Nets and other models of concurrency (ATPN06), Turku, Finland, June 26-30, 2006. Proceedings; Editors: Susanna Donatelli, P. S. Thiagarajan; LNCS 4024 / 2006, pp. 181-200, ISBN: 3-540-34699-6 DOI: 10.1007/11767589

Some more case studies

  1. Q Gao, F Liu, D Gilbert, M Heiner, D Tree (2011): A Multiscale Approach to Modelling Planar Cell Polarity in Drosophila Wing using Hierarchically Coloured Petri Nets; In Proc. 9th International Conference on Computational Methods in Systems Biology (CMSB 2011), Paris, ACM digital library, to appear, September 2011.
  2. M Heiner and K Sriram (2010): Structural Analysis to Determine the Core of Hypoxia Response Network; PLoS ONE, 5(1):e8600, 2010.
  3. D Gilbert, M Heiner, S Rosser, R Fulton, X Gu and M Trybio (2008): A Case Study in Model-driven Synthetic Biology; In IFIP WCC 2008, 2nd IFIP Conference on Biologically Inspired Collaborative Computing (BICC 2008), Milano, Springer, IFIP, volume 268, pages 163–175, September 2008

Registration / Fee / Accommodation

Register for ICSB and tutorials/workshop

Register only for tutorials/workshop

Fee:

 Tutorial 20Tutorial 21
Tutorial + ICSB45 €45 €
Tutorial ONLY75 €75 €

Online registration closes by August 23, 2011.

Questions

Contact: mary-ann.blaetke (at) ovgu.de

Downloads

Flyer Petri Net Tutorial at ICSB 2011

… the end …

Any comments or questions are welcome. Please direct them to monika.heiner@b-tu.de