Investigating Co-infection Dynamics through Evolution of Bio-PEPA Model Parameters: A Combined Process Algebra and Evolutionary Computing Approach

Process algebras are an effective method for defining models of complex interacting biological processes, but defining a model requires expertise from both modeller and domain expert. In addition, even with the right model, tuning parameters to allow model outputs to match experimental data can be difficult. This is the well-known parameter fitting problem. Evolutionary algorithms provide effective methods for finding solutions to optimisation problems with large search spaces and are well suited to investigating parameter fitting problems. We present the Evolving Process Algebra EPA framework which combines an evolutionary computation approach with process algebra modelling to produce parameter distribution data that provides insight into the parameter space of the biological system under investigation. The EPA framework is demonstrated through application to a novel example: T helper cell activation in the immune system in the presence of co-infection.

[1]  David E. Goldberg,et al.  Genetic Algorithms in Search Optimization and Machine Learning , 1988 .

[2]  David Corne,et al.  Evolutionary Computation In Bioinformatics , 2003 .

[3]  Jos C. M. Baeten,et al.  A brief history of process algebra , 2005, Theor. Comput. Sci..

[4]  Carron Shankland,et al.  Evolving Bio-PEPA process algebra models using genetic programming , 2012, GECCO '12.

[5]  Alex Fraser,et al.  Simulation of Genetic Systems by Automatic Digital Computers I. Introduction , 1957 .

[6]  David R. B. Stockwell,et al.  Genetic Algorithms II , 1999 .

[7]  John H. Holland,et al.  Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence , 1992 .

[8]  Jane Hillston,et al.  A compositional approach to performance modelling , 1996 .

[9]  Adelinde M. Uhrmacher,et al.  A flexible and scalable experimentation layer , 2008, 2008 Winter Simulation Conference.

[10]  Jacques Cohen,et al.  The crucial role of CS in systems and synthetic biology , 2008, CACM.

[11]  W. Paul,et al.  Heterogeneity and plasticity of T helper cells , 2010, Cell Research.

[12]  As Fraser,et al.  Simulation of Genetic Systems by Automatic Digital Computers VII. Effects of Reproductive Ra'l'e, and Intensity of Selection, on Genetic Structure , 1960 .

[13]  A. Graham,et al.  IL-4 is required to prevent filarial nematode development in resistant but not susceptible strains of mice. , 2002, International journal for parasitology.

[14]  Paolo Milazzo,et al.  The Calculus of Looping Sequences , 2008, SFM.

[15]  Brian J. Ross,et al.  Evolving stochastic processes using feature tests and genetic programming , 2009, GECCO.

[16]  M. Yazdanbakhsh,et al.  Co‐infection of helminths and malaria: modulation of the immune responses to malaria , 2006, Parasite immunology.

[17]  Miguel Rocha,et al.  Modeling formalisms in Systems Biology , 2011, AMB Express.

[18]  D. E. Goldberg,et al.  Genetic Algorithms in Search, Optimization & Machine Learning , 1989 .

[19]  Michael A. Gibson,et al.  Efficient Exact Stochastic Simulation of Chemical Systems with Many Species and Many Channels , 2000 .

[20]  I. Chou,et al.  Recent developments in parameter estimation and structure identification of biochemical and genomic systems. , 2009, Mathematical biosciences.

[21]  F. Finkelman,et al.  Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models. , 1997, Annual review of immunology.

[22]  John H. Holland,et al.  Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence , 1992 .

[23]  Carron Shankland,et al.  A rigorous approach to investigating common assumptions about disease transmission , 2010, Theory in Biosciences.

[24]  Corrado Priami,et al.  Process Calculi and Life Science , 2006, APC 25.

[25]  Adam Duguid,et al.  Design and development of software tools for Bio-PEPA , 2009, Proceedings of the 2009 Winter Simulation Conference (WSC).

[26]  Kenneth de Jong,et al.  Evolutionary computation: a unified approach , 2007, GECCO.

[27]  Zbigniew Michalewicz,et al.  Evolutionary Computation 2 : Advanced Algorithms and Operators , 2000 .

[28]  Carron Shankland,et al.  Optimisation of process algebra models using evolutionary computation , 2011, 2011 IEEE Congress of Evolutionary Computation (CEC).

[29]  Jane Hillston,et al.  Bio-PEPA: A framework for the modelling and analysis of biological systems , 2009, Theor. Comput. Sci..