Evolving Cell Signaling Networks in Silico

The ESIGNET project (Evolving Cell Signaling Networks in Silico) is a Specific Targeted Research Project funded by the European Commission under the Sixth Framework Programme.

The overall goal of this project is to study the computational properties of CSNs by evolving them using methods from evolutionary computation, and to re-apply this understanding in developing new ways to model and predict real CSNs. The project is highly interdisciplinary. Its completion requires insight into the subject from many points of views. The research will be at the interface of (at least) Biology, Computer Science, and Control Engineering. It also utilises a plethora of approaches and methods. The high potential of the proposal is largely due to the co-ordinated and concerted multi-disciplinary and methodological approaches. This is reflected in the composition of the consortium. All researchers in this consortium have previously been involved in research at the interface between Computer Science and Biology and have a strong ability to integrate insights from those fields.

We acknowledge with thanks the Systems Biology Institute, Tokyo, Japan for permission to use the graphic image above.

The ESIGNET project investigates the possibility to computationally evolve and simulate artificial cell signaling networks (CSNs) with pre-specified properties by means of Evolutionary Computation methods. It is required that the interactions between the simulated particles in the artificial chemistry are realistic with respect to the interactions found in real CSNs. In this project an artificial intelligence predictor for unknown components of cell signaling networks in organisms will be built.

CSNs are of fundamental importance for our understanding of organismic processes and for medical research (understanding of diseases, development of effective drugs). A general and theoretical understanding of CSNs is currently missing: ESIGNET aims to fill this gap, with potential benefits in terms of improved research and modelling methods and new applications and techniques. The impact of the project is not limited to computer science and Biology, but will contribute to a number of emerging fields of science and technology; examples are nano-technology and intelligent drug delivering systems. The opportunities of the research are thus far reaching. Understanding how distributed systems of chemically interacting particles perform computations is a necessary condition for our ability to construct molecular wetware computers in vitro and incorporate them into future technology. Even in the case that not all of these applications will be realised, most workpackages contain fall-back research topics that will yield valuable scientific output even if the highest level of ambition might not be satisfied.

Publication list

List of publications from the ESIGNET members (produced from 1.9.2005 to 28.2.2007):

• Paenke, I., Sendhoff, B., Rowe, J., Fernando, C. (2007) On the Adaptive Disadvantage of Lamarckianism in Rapidly Changing Environments. (Submitted to ECAL 2007) Download pdf.
• Fernando, C, Rowe, J. (2007) Hebbian Learning in a Gene Circuit. (GECCO 2007).
• Fernando, C., Jones, B. Stekel, D. (2007) Is there a Liquid State Machine in the Bacterium Escherichia Coli? (Submitted to IEEE Artificial Life, April 2007). Download draft here.
• Fernando, C., and Rowe, J. (2006) Natural Selection in Chemical Evolution. (To appear in Journal of Theoretical Biology, accepted January 2007).
• Fernando, C., Von Kiedrowski, G. and Szathmary E. (2006).Tidal Cycling and the Origin of Life: 'Elongators' Sequester Replicators. (To appear in Journal of Molecular Evolution, September, 2006)
  
• Fernando, C. and Penn, A. (2006) The Origin of Autonomy at the Chemical and Ecosystem Levels. (Autonomy Workshop Paper, Artifiicial Life X, Bloomington, Indiana, USA).
  
• Maron, M. and Fernando, C. (2006) Food Webs and the Evolution of Organism Complexity. (Complexity Workshop Paper, Artificial Life X, Bloomington, Indiana, USA).
• Liekens, A.M.L. and Fernando, C. (2006) Turing Complete Catalytic Particle Computers. (ECAL 2007).
• Rowe, J.E., Vose, M.D. and Wright, A.H. (2006). Differentiable coarse graining. Theoretical Computer Science vol.361, pages 111-129.
• Rowe J.E., Vose, M.D. and Wright, A.H. (2007) Neighbourhood graphs and symmetric genetic operators. Foundations of Genetic Algorithms 9 (to appear).

• J. Decraene, G. Mitchell, C. Kelly and B. McMullin. "An approach to evolving cell signaling networks in silico." International Workshop on Systems Biology 2006. 17-19 July 2006, Maynooth, Ireland.
• C. Kelly, J. Decraene, G. Mitchell, B. McMullin and D. O'Brien. "Cellular computation using classifier systems." International Workshop on Systems Biology 2006. 17-19 July 2006, Maynooth, Ireland.
• J.Decraene, G.G.Mitchell, C.Kelly and B.McMullin. "Evolving Artificial Cell Signaling Networks". European Conference on Complex Systems, ECCS-06, 25-29 September 2006, Oxford
• J. Decraene, P. Dittrich, T. Hinze, T. Lenser, B. McMullin, G. Mitchell. "A Multidisciplinary Survey of Modeling Techniques for Biochemical Networks". Integrative Post-Genomics Conference, IPG06. 29 November - 1 December 2006, Lyon, France.
• J.Decraene, G.G.Mitchell and B.McMullin. "Evolving Artificial Cell Signaling Networks using Molecular Classifier Systems". Bionetics 2006 Conference (Bio Inspired mOdels of NEtwork, Information and Computing Systems).
• J.Decraene. "The Holland Broadcast Language and the modeling of biochemical network". EuroGP 2007 - 10th European conference on Genetic Programming. 11-13 April, Valencia, Spain.
• G.Mitchell. "Quality Time Tradeoff Operator for Designing Efficient Multi Level Genetic Algorithms". 1-11 July, 1007, London, UK.
• J.Decraene, G.G. Mitchell, Barry McMullin, "Evolving Artificial Cell Signaling Networks: Perspective and Methods" In /F. Dressler and I. Carreras (eds.) Advances in Biologically Inspired Information Systems: Models, Methods, and Tools/, Springer, 2007.
• J. Decraene, "The Holland Broadcast Language", Technical report ALL-06-01, ALife Lab, RINCE, School of Electronic Engineering, Dublin City University, 2006
• J. Decraene, P. Dittrich, T. Hinze, T. Lenser, B. McMullin, G. Mitchell. A Multidisciplinary Survey of Modeling Techniques for Biochemical Networks. Integrative Post-Genomics (IPG'06), Lyon, France, 2006.

• T. Lenser, T. Hinze, B. Ibrahim, P. Dittrich. "Towards Evolutionary Network Reconstruction Tools for Systems Biology". In E. Marchiori, J.H. Moore, J.C. Rajapakse (eds.), Proceedings EvoBIO 2007, Series Lecture Notes in Computer Science, Vol. 4447, pp. 132-142, Springer, 2007
• T. Hinze, S. Hayat, T. Lenser, N. Matsumaru, P. Dittrich. "AHL Induced Gene Regulatory Networks: From an in vivo Flip-Flop Implementation to Programmable Computing Agents". submitted 2007
• J. Decraene, P. Dittrich, T. Hinze, T. Lenser, B. McMullin, G. Mitchell. "A Multidisciplinary Survey of Modeling Techniques for Biochemical Networks". Proceedings Integrative Post-Genomics (IPG'06), p. 19, INSA Lyon-France, 2006
• T. Hinze, T. Lenser, P. Dittrich. "Zellsignalnetzwerke - Biologische Computer mit universeller Berechnungsstaerke". In R. Freund, M. Oswald (Hrsg.), Proceedings 16. Theorietag Automaten und Formale Sprachen pp. 73-77, TU Wien, 2006 (in German)
• T. Hinze, T. Lenser, P. Dittrich. "A Protein Substructure Based P System for Description and Analysis of Cell Signalling Networks". In H.J. Hoogeboom, G. Paun, G. Rozenberg, A. Salomaa (eds.), Proceedings Seventh Workshop on Membrane Computing (WMC7), Series Lecture Notes in Computer Science, Vol. 4361, pp. 409-423, Springer, 2006
• N. Matsumaru, T. Lenser, T. Hinze, P. Dittrich. "Designing a chemical program using chemical organization theory". accepted for Proceedings BioSysBio (Systems Biology, Bioinformatics, Synthetic Biology) to appear as special issue of BMC Bioinformatics, 2007
• C. Schmidt, T. Hinze, T. Lenser, P. Dittrich. "Selected Public Databases and Software Tools with Relevance to the ESIGNET Project." Technical Report on Computer Science 06-24, FSU Jena, 2006

• D. Bosnacki and S. Leue and A. Lluch Lafuente, "Partial-Order Reduction for General State Exploring Algorithms", Model Checking Software SPIN 2006, Lecture Notes in Computer Science 3925:271-287, 2006
• G.J. Holzmann and D. Bosnacki, "Multi-core Model Checking with SPIN", Proceedings of HIPS-TopModels, 2007
• H.J. Buisman, H.M.M. ten Eikelder, P.A.J. Hilbers, A.M.L. Liekens, "Computing Algebraic Functions with Biochemical Reaction Networks", Artificial Life Journal, Special Issue on Artificial Chemistries, 2007
• H.M.M. ten Eikelder, S.P.M. Crijns, M.N. Steijaert, A.M.L. Liekens, P.A.J. Hilbers, "Computing with Feedforward Networks of Artificial Biochemical Neurons", submitted to International Conference on Artificial Neural Networks (ICANN 2007), 2007
• A.M.L. Liekens, C.T. Fernando, "Turing Complete Catalytic Particle Computers", submitted to European Conference on Artificial Life (ECAL 2007), 2007
• D. Bosnacki and S. Leue and A. Lluch Lafuente, "Partial-Order Reduction for General State Exploring Algorithms", to appear in International Journal of Software Tools for Technology Transfer (STTT), Springer, 2007
• G. Holzmann and D. Bosnacki, "Multi-core Model Checking with Spin", submitted to IEEE Transactions on Software Engineering, 2007
• T.E.Pronk, E.P. de Vink, D. Bosnacki, T.M. Breit, "Stochastic Modeling of Codon Bias with PRISM", submitted to MTCoord, 2007