In silico evolution of functional modules in biochemical networks.

Understanding the large reaction networks found in biological systems is a daunting task. One approach is to divide a network into more manageable smaller modules, thus simplifying the problem. This is a common strategy used in engineering. However, the process of identifying biological modules is still in its infancy and very little is understood about the range and capabilities of motif structures found in biological modules. In order to delineate these modules, a library of functional motifs has been generated via in silico evolution techniques. On the basis of their functional forms, networks were evolved from four broad areas: oscillators, bistable switches, homeostatic systems and frequency filters. Some of these motifs were constructed from simple mass action kinetics, others were based on Michaelis-Menten kinetics as found in protein/protein networks and the remainder were based on Hill equations as found in gene/protein interaction networks. The purpose of the study is to explore the capabilities of different network architectures and the rich variety of functional forms that can be generated. Ultimately, the library may be used to delineate functional motifs in real biological networks.

[1]  Irene A. Stegun,et al.  Handbook of Mathematical Functions. , 1966 .

[2]  K. S. Kölbig,et al.  Errata: Milton Abramowitz and Irene A. Stegun, editors, Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables, National Bureau of Standards, Applied Mathematics Series, No. 55, U.S. Government Printing Office, Washington, D.C., 1994, and all known reprints , 1972 .

[3]  R Heinrich,et al.  Metabolic regulation and mathematical models. , 1977, Progress in biophysics and molecular biology.

[4]  J. Stucki,et al.  Stability analysis of biochemical systems--a practical guide. , 1978, Progress in biophysics and molecular biology.

[5]  M. A. Shea,et al.  The OR control system of bacteriophage lambda. A physical-chemical model for gene regulation. , 1985, Journal of molecular biology.

[6]  Gene F. Franklin,et al.  Feedback Control of Dynamic Systems , 1986 .

[7]  J. Hervagault,et al.  Bistability and irreversible transitions in a simple substrate cycle. , 1987, Journal of theoretical biology.

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

[9]  Steven H. Strogatz,et al.  Nonlinear Dynamics and Chaos , 2024 .

[10]  Ed Anderson,et al.  LAPACK Users' Guide , 1995 .

[11]  Y. Kuznetsov Elements of Applied Bifurcation Theory , 2023, Applied Mathematical Sciences.

[12]  Thomas Wilhelm,et al.  Smallest chemical reaction system with Hopf bifurcation , 1995 .

[13]  A. Goldbeter,et al.  Biochemical Oscillations And Cellular Rhythms: Contents , 1996 .

[14]  A. Arkin,et al.  It's a noisy business! Genetic regulation at the nanomolar scale. , 1999, Trends in genetics : TIG.

[15]  James Demmel,et al.  LAPACK Users' Guide, Third Edition , 1999, Software, Environments and Tools.

[16]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[17]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[18]  B. Kholodenko,et al.  Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades. , 2000, European journal of biochemistry.

[19]  J. Doyle,et al.  Robust perfect adaptation in bacterial chemotaxis through integral feedback control. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  James M. Bower,et al.  Computational modeling of genetic and biochemical networks , 2001 .

[21]  A. Goldbeter,et al.  From simple to complex oscillatory behavior in metabolic and genetic control networks. , 2001, Chaos.

[22]  C. Rao,et al.  Control, exploitation and tolerance of intracellular noise , 2002, Nature.

[23]  J. Ferrell Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. , 2002, Current opinion in cell biology.

[24]  Eduardo Sontag,et al.  Untangling the wires: A strategy to trace functional interactions in signaling and gene networks , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Goldbeter Computational approaches to cellular rhythms , 2002, Nature.

[26]  Katherine C. Chen,et al.  Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. , 2003, Current opinion in cell biology.

[27]  Francesc Sagués,et al.  Nonlinear chemical dynamics , 2003 .

[28]  Hiroaki Kitano,et al.  Next generation simulation tools: the Systems Biology Workbench and BioSPICE integration. , 2003, Omics : a journal of integrative biology.

[29]  A. Arkin,et al.  Motifs, modules and games in bacteria. , 2003, Current opinion in microbiology.

[30]  Mads Kærn,et al.  Noise in eukaryotic gene expression , 2003, Nature.

[31]  J. Vilar,et al.  From molecular noise to behavioural variability in a single bacterium , 2004, Nature.

[32]  H. Sauro,et al.  Conservation analysis in biochemical networks: computational issues for software writers. , 2004, Biophysical chemistry.

[33]  Farren J. Isaacs,et al.  Synthetic biology evolves. , 2004, Trends in biotechnology.

[34]  H. Sauro,et al.  Preliminary Studies on the In Silico Evolution of Biochemical Networks , 2004, Chembiochem : a European journal of chemical biology.

[35]  V. Hakim,et al.  Design of genetic networks with specified functions by evolution in silico. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M E J Newman,et al.  Finding and evaluating community structure in networks. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[37]  B. Ingalls A Frequency Domain Approach to Sensitivity Analysis of Biochemical Networks , 2004 .

[38]  Herbert M. Sauro,et al.  Bifurcation discovery tool , 2005, Bioinform..