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An Accelerated Method for Simulating Population Dynamics

Published online by Cambridge University Press:  03 June 2015

Daniel A. Charlebois*
Affiliation:
Department of Physics, University of Ottawa, 150 Louis Pasteur, Ottawa, Ontario K1N 6N5, Canada Ottawa Institute of Systems Biology, University of Ottawa, 451 Symth Road, Ottawa, Ontario K1H 8M5, Canada
Mads Kærn*
Affiliation:
Department of Physics, University of Ottawa, 150 Louis Pasteur, Ottawa, Ontario K1N 6N5, Canada Ottawa Institute of Systems Biology, University of Ottawa, 451 Symth Road, Ottawa, Ontario K1H 8M5, Canada Department of Cellular and Molecular Medicine, University of Ottawa, 451 Symth Road, Ottawa, Ontario K1H 8M5, Canada
*
Corresponding author.Email:[email protected]
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Abstract

We present an accelerated method for stochastically simulating the dynamics of heterogeneous cell populations. The algorithm combines a Monte Carlo approach for simulating the biochemical kinetics in single cells with a constant-number Monte Carlo method for simulating the reproductive fitness and the statistical characteristics of growing cell populations. To benchmark accuracy and performance, we compare simulation results with those generated from a previously validated population dynamics algorithm. The comparison demonstrates that the accelerated method accurately simulates population dynamics with significant reductions in runtime under commonly invoked steady-state and symmetric cell division assumptions. Considering the increasing complexity of cell population models, the method is an important addition to the arsenal of existing algorithms for simulating cellular and population dynamics that enables efficient, coarse-grained exploration of parameter space.

Type
Research Article
Copyright
Copyright © Global Science Press Limited 2013

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References

[1]Acar, M., Mettetal, J. T. and Oudenaarden, A. van, Stochastic switching as a survival strategy in fluctuating environments, Nat. Genet., 40 (2008), 471475.Google Scholar
[2]Blake, W., Balazsi, G., Kohanski, M., Isaacs, F., Murphy, K., Kuang, Y., Cantor, C., Walt, D. and Collins, J., Phenotypic consequences of promoter-mediated transcriptional noise, Mol. Cell, 24 (2006), 853865.CrossRefGoogle ScholarPubMed
[3]Boman, B. M., Wicha, M. S., Fields, J. Z. and Runquist, O. A., Symmetric division of cancer stem cells - a key mechanism in tumor growth that should be targeted in future therapeutic approaches, Clinical Pharmacology and Therapeutics, 81 (2007), 893898.Google Scholar
[4]Charlebois, D. A, Intosalmi, J., Fraser, D. and Kaern, M., An algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics, Commun. Comput. Phys., 9 (2011), 89112.Google Scholar
[5]Charlebois, D. A, Abdennur, N. and Kaern, M., Gene expression noise facilitates adaptation and drug resistance independently of mutation, Phys. Rev. Lett., 107 (2011), doi: 10.1103/Phys-RevLett.107.218101.CrossRefGoogle ScholarPubMed
[6]Ribeiro, A. S., Charlebois, D. A. and Lyold-Price, J., CellLine, a stochastic cell lineage simulator, Bioinformatics, 23 (2007), 34093411.Google Scholar
[7]Eldar, A. and Elowitz, M., Functional roles for noise in genetic circuits, Nature, 467 (2010), 167173.Google Scholar
[8]Feierbach, B. and Chang, F., Roles of the fission yeast formin for3p in cell polarity, actin cable formation and symmetric cell division, Curr. Biol., 11 (2001), 16561665.Google ScholarPubMed
[9]Fraser, D. and Kaern, M., A chance at survival: gene expression noise and phenotypic diversification strategies, Molec. Microbiol., 71 (2009), 13331340.Google Scholar
[10]Gillespie, D. T., A general method for numerically simulating the stochastic time evolution of coupled chemical reactions, J. Comput. Phys., 22 (1976), 403434.CrossRefGoogle Scholar
[11]Gillespie, D. T., Exact stochastic simulation of coupled chemical reactions, J. Phys. Chem., 81 (1977), 23402361.Google Scholar
[12]Lu, T., Volfson, D., Tsimring, L. and Hasty, J., Cellular growth and division in the Gillespie algorithm, Syst. Biol., 1 (2004), 121128.Google Scholar
[13]Volfson, D., Marciniak, J.1, Blake, W. J., Ostroff, N.1, Tsimring, L. S. and Hasty, J., Origins of extrinsic variability in eukaryotic gene expression, Nature, 439 (2006), 861864.CrossRefGoogle ScholarPubMed
[14]Huttner, W. B. and Kosodo, Y., Symmetric versus asymmetric cell division during neurogenesis in the developing vertebrate central nervous system, Curr. Opin. Cell. Biol., 17 (2005), 648657.Google Scholar
[15]Kaern, M., Elston, T. C., Blake, W. J. and Collins, J. J., Stochasticity in gene expression, Nat. Rev. Genet., 6 (2005), 451464.Google Scholar
[16]Kaufmann, B. B. and Oudenaarden, A. van, Stochastic gene expression: from single molecules to the proteome, Curr. Opin. Genet. Dev., 17 (2007), 107112.CrossRefGoogle Scholar
[17]Lin, Y., Lee, K. and Matsoukas, T., Solution of the population balance equation using constant-number Monte Carlo, Chem. Eng. Sci., 57 (2002), 22412252.Google Scholar
[18]Lu, T., Volfson, D., Tsimring, L. and Hasty, J., Cellular growth and division in the Gillespie algorithm, Syst. Biol., 1 (2004), 121128.CrossRefGoogle ScholarPubMed
[19]Nevozhay, D., Adams, R. M., Itallie, E. V., Bennett, M. R. and Balazsi, G., Mapping the environmental fitness landscape of a synthetic gene circuit, PLoS Comput. Biol., 8 (2012), doi:10.1371/journal.pcbi.1002480.Google Scholar
[20]Maheshri, N. and O’Shea, E. K., Living with noisy genes: how cells function reliably with inherent variability in gene expression, Annu. Rev. BioPhys. Biomol. Struct., 36 (2007), 413434.Google Scholar
[21]Mantzaris, N. V., Stochastic and deterministic simulations of heterogeneous cell population dynamics, J. Theor. Biol., 241 (2006), 690706.Google Scholar
[22]Mantzaris, N. V., From single-cell genetic architecture to cell population dynamics: Quantitatively decomposing the effects of different population heterogeneity sources for a genetic network with positive feedback architecture, BioPhys. J., 92 (2007), 42714288.Google Scholar
[23]McKay, M. D., Beckman, R. J. and Conover, W. J., A comparison of three methods for selecting values of input variables in the analysis of output from a computer code, Technometrics, 21 (1979), 239245.Google Scholar
[24]McKay, M. D., Sensitivity and uncertainty analysis using a statistical sample of input values, in: Ronen, Y. (Ed.), Uncertainty Analysis, Ch. 4, pp. 145186, CRC Press, Bcca Raton, Florida, 1988.Google Scholar
[25]Murugan, R., Multiple stochastic point processes in gene expression, J. Stat. Phys., 131 (2008), 153165.Google Scholar
[26]Paulsson, J., Summing up the noise in gene networks, Nature, 427 (2004), 415418.Google Scholar
[27]Raser, J. M. and O’Shea, E. K., Control of stochasticity in eukaryotic gene expression, Science, 304 (2004), 18111814.Google Scholar
[28]Ramkrishna, D., The status of population balances, Rev. Chem. Engng., 3 (1985), 4995.Google Scholar
[29]Samoilov, M. S., Price, G. and Arkin, A. P., From fluctuations to phenotypes: The physiology of noise, Sci. STKE, 366 (2006), re17.Google Scholar
[30]Scott, M., Ingalls, B. and Kaern, M., Estimations of intrinsic and extrinsic noise in models of nonlinear genetic networks, Chaos, 16 (2006), 026107.Google Scholar
[31]Shahrezaei, V. and Swain, P. S., Analytical distributions for stochastic gene expression, PNAS, 105 (2008), 1725617261.Google Scholar
[32]Shahrezaei, V., Ollivier, J. and Swain, P.Colored extrinsic fluctuations and stochastic gene expression, Mol. Syst. Biol., 4 (2008), 196.CrossRefGoogle ScholarPubMed
[33]Sigal, A., Milo, R., Cohen, A., Geva-Zatorsky, N., Klein, Y., Liron, Y., Rosenfeld, N., Danon, T., Perzov, N. and Alon, U., Variability and memory of protein levels in human cells, Nature, 444 (2006), 643646.CrossRefGoogle ScholarPubMed
[34]Smith, M. and Matsoukas, T., Constant-number Monte Carlo simulation of population balances, Chem. Eng. Sci., 53 (1998), 17771786.Google Scholar
[35]Spudich, J. L. and Koshland, D. E., Non-genetic individuality: chance in the single cell, Nature, 262 (1976), 467471.CrossRefGoogle ScholarPubMed
[36]Swain, P. S., Elowits, M. B. and Siggia, E. D., Intrinsic and extrinsic contributions to stochasticity in gene expression, PNAS, 99 (2002), 1279512800.Google Scholar
[37]Thattai, M. and Oudenaarden, A. van, Attenuation of noise in ultrasensitive signaling cascades, BioPhys. J., 82 (2002), 29432950.Google Scholar
[38]Uhlenbeck, G. and Ornstein, L., On the theory of Brownian motion, Phys. Rev., 36 (2008), 823841.Google Scholar
[39]Woolner, S. and Papalopulu, N., Spindle position in symmetric cell divisions during epiboly is controlled by opposing and dynamic apicobasal forces, Dev. Cell, 22 (2009), 775787.Google Scholar
[40]Zadrag-Tecza, R., Kwolek-Mirek, M., Bartosz, G. and Bilinski, T., Cell volume as a factor limiting the replicative lifespan of the yeast Saccharomyces cerevisiae, Biogerontology, 10 (2009), 481488.Google Scholar
[41]Zhang, Z., Qian, W. and Zhang, J., Positive selection for elevated gene expression noise in yeast, Mol. Syst. Biol., (2009), doi:10.1038/msb.2009.58.Google Scholar
[42]Zhuravel, D., Fraser, D., St-Pierre, S., Tepliakova, L., Pang, W., Hasty, J. and Kaern, M., Phenotypic impact of regulatory noise in cellular stress-response pathways, Syst. Synth. Biol., 4 (2010), doi:10.1007/s11693-010-9055-2.Google Scholar