A Compositional Approach to the Stochastic Dynamics of Gene Networks

We propose a compositional approach to the dynamics of gene regu-latory networks based on the stochastic π-calculus, and develop a representation of gene network elements which can be used to build complex circuits in a transparent and efficient way. To demonstrate the power of the approach we apply it to several artificial networks, such as the repressilator and combinatorial gene circuits first studied in Combinatorial Synthesis of Genetic Networks [1]. For two examples of the latter systems, we point out how the topology of the circuits and the interplay of the stochastic gate interactions influence the circuit behavior. Our approach may be useful for the testing of biological mechanisms proposed to explain the experimentally observed circuit dynamics.

[1]  E Friedman,et al.  Loose ends. , 2020, The Healthcare Forum journal.

[2]  Robin Milner,et al.  Communicating and mobile systems - the Pi-calculus , 1999 .

[3]  M. Thattai,et al.  Intrinsic noise in gene regulatory networks , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Luca Cardelli,et al.  A Correct Abstract Machine for the Stochastic Pi-calculus , 2004 .

[5]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[6]  Dennis Bray Reasoning for results , 2006 .

[7]  Luca Cardelli,et al.  BioAmbients: an abstraction for biological compartments , 2004, Theor. Comput. Sci..

[8]  Linyong Mao,et al.  Probabilistic representation of gene regulatory networks , 2004, Bioinform..

[9]  M. Elowitz,et al.  Combinatorial Synthesis of Genetic Networks , 2002, Science.

[10]  E. Shapiro,et al.  Cellular abstractions: Cells as computation , 2002, Nature.

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

[12]  Y. Lazebnik Can a biologist fix a radio? — or, what I learned while studying apoptosis , 2004, Biochemistry (Moscow).

[13]  Davide Sangiorgi,et al.  Communicating and Mobile Systems: the π-calculus, , 2000 .

[14]  Luca Cardelli,et al.  Brane Calculi Interactions of Biological Membranes , 2004 .

[15]  Joachim Niehren,et al.  Gene Regulation in the Pi Calculus: Simulating Cooperativity at the Lambda Switch , 2006, Trans. Comp. Sys. Biology.

[16]  D. Gillespie Exact Stochastic Simulation of Coupled Chemical Reactions , 1977 .

[17]  Bud Mishra,et al.  Wild by Nature , 2002, Science.

[18]  Pierpaolo Degano,et al.  VICE: A VIrtual CEll , 2004, CMSB.

[19]  U. Alon,et al.  Assigning numbers to the arrows: Parameterizing a gene regulation network by using accurate expression kinetics , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  W. J. EGGELING Wild Nature , 1966, Nature.

[21]  M. Ehrenberg,et al.  Stochastic focusing: fluctuation-enhanced sensitivity of intracellular regulation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.