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Executable Modeling of Morphogenesis : A Turing-Inspired Approach

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Języki publikacji
EN
Abstrakty
EN
In his pioneering 1952 paper, ”The chemical basis of morphogenesis”, Alan Turing introduced, perhaps for the first time, a model of the morphogenesis of embryo development. Central to his theory is the concept of cells with chemical entities that interact with morphogens to drive embryonic development through changes in what he termed ’the state of the system’. Turing’s concepts have inspired many mathematical and computational models proposed since then. Here we discuss the way Turing’s ideas inspired our approach to the state-based modeling of morphogenesis, which results in a fully executable program for the interactions between chemical entities and morphogens. As a representative example we describe our modeling of pancreatic organogenesis, a complex developmental process that develops from a flat sheet of cells into a 3D cauliflower-like shape. We show how we constructed the model and tested the relations between morphogens and cells, and illustrate the analysis of the model against experimental data. Finally, we discuss a variant of the original Turing-Test for a machine’s ability to demonstrate intelligence as a future means to validate computerized biological models, like the one presented here.
Słowa kluczowe
Wydawca
Rocznik
Strony
403--417
Opis fizyczny
Bibliogr. 33 poz., rys.
Twórcy
autor
autor
autor
  • Department of Computer Science and Applied Mathematics andWeizmann, Institute of Science, Rehovot 76100, Israel, yaki.setty@gmail.com
Bibliografia
  • [1] Turing, A.M.: The chemical basis of morphogenesis. Philosophical Transactions of the Royal Society of London. B 1952. 327: p. 37-72.
  • [2] Turing, A.M.: The chemical basis of morphogenesis. 1953. Bulletin of mathematical biology, 1990. 52(1-2): p. 153-97; discussion 119-52.
  • [3] Caicedo-Carvajal, C.E. and T. Shinbrot: In silico zebrafish pattern formation. Developmental biology, 2008. 315(2): p. 397-403.
  • [4] Shinbrot, T., et al.: Cellular morphogenesis in silico. Biophysical journal, 2009. 97(4): p. 958-67.
  • [5] Swindale, N.V.: A model for the formation of ocular dominance stripes. Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society, 1980. 208(1171): p. 243-64.
  • [6] Bonabeau, E.: From classical models of morphogenesis to agent-based models of pattern formation. Artificial life, 1997. 3(3): p. 191-211.
  • [7] Smith, B.J. and D.P. Gaver, 3rd, Agent-based simulations of complex droplet pattern formation in a twobranch microfluidic network. Lab on a chip, 2010. 10(3): p. 303-12.
  • [8] Fortuna, S. and A. Troisi: An artificial intelligence approach for modeling molecular self-assembly: agentbased simulations of rigid molecules. The journal of physical chemistry. B, 2009. 113(29): p. 9877-85.
  • [9] Setty, Y., et al.: Four-dimensional realistic modeling of pancreatic organogenesis. Proceedings of the National Academy of Sciences of the United States of America, 2008. 105(51): p. 20374-9.
  • [10] Setty, Y., et al.: A model of stem cell population dynamics: in-silico analysis and in-vivo validation. Development, 2011: p. In Press.
  • [11] Setty, Y., et al.: How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex. BMC systems biology, 2011. Under Review.
  • [12] Harel, D.: Statecharts: A visual formalism for complex systems. Sci. Comput. Program., 1987. 8(3): p. 231-274.
  • [13] Efroni, S., H. David, and C.I. R.: Reactive Animation: Realistic Modeling of Complex Dynamic Systems. Computer, 2005. 38(1): p. 38-47.
  • [14] Harel, D. and Y. Setty: Generic Reactive Animation: Realistic Modeling of Complex Natural Systems, in Proceedings of the 1st international workshop on Formal Methods in Systems Biology 2008, Springer-Verlag: Cambridge, UK. p. 1-16.
  • [15] Pictet, R.L., et al.: An ultrastructural analysis of the developing embryonic pancreas. Developmental biology, 1972. 29(4): p. 436-67.
  • [16] Jensen, J.: Gene regulatory factors in pancreatic development. Developmental dynamics : an official publication of the American Association of Anatomists, 2004. 229(1): p. 176-200.
  • [17] Slack, J.M.: Developmental biology of the pancreas. Development, 1995. 121(6): p. 1569-80.
  • [18] Kim, S.K., M. Hebrok, and D.A. Melton: Notochord to endoderm signaling is required for pancreas development. Development, 1997. 124(21): p. 4243-52.
  • [19] Kim, S.K. and M. Hebrok: Intercellular signals regulating pancreas development and function. Genes & development, 2001. 15(2): p. 111-27.
  • [20] Kim, S.K. and R.J. MacDonald: Signaling and transcriptional control of pancreatic organogenesis. Current opinion in genetics & development, 2002. 12(5): p. 540-7.
  • [21] Edlund, H.: Pancreatic organogenesis-developmental mechanisms and implications for therapy. Nature reviews. Genetics, 2002. 3(7): p. 524-32.
  • [22] Bollobas, B.: Random Graphs. Cambridge University Press, 2001.
  • [23] Harel, D.: A grand challenge: full reactive modeling of a multi-cellular animal, in Proceedings of the 6th international conference on Hybrid systems: computation and control 2003, Springer-Verlag: Prague, Czech Republic. p. 2-2.
  • [24] Turing, A.M.: Computing Machinery and Intelligence. Mind 1950. 236: p. 433-460.
  • [25] Nakamasu, A., et al.: Interactions between zebrafish pigment cells responsible for the generation of Turing patterns. Proceedings of the National Academy of Sciences of the United States of America, 2009. 106(21): p. 8429-34.
  • [26] Klika, V., et al.: The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation. Bulletin of mathematical biology, 2011.
  • [27] Liu, H., et al.: Pattern formation in the iodate-sulfite-thiosulfate reaction-diffusion system. Physical chemistry chemical physics : PCCP, 2011.
  • [28] Gravn, C.P. and R. Lahoz-beltra: Evolving morphogenetic fields in the zebra skin pattern based on Turing's morphogen hypothesis Int. J. Appl. Math. Comput. Sci., 2004. 14(3): p. 351-361.
  • [29] Howard, J., S.W. Grill, and J.S. Bois: Turing's next steps: the mechanochemical basis of morphogenesis. Nature reviews. Molecular cell biology, 2011. 12(6): p. 392-8.
  • [30] Harris, A.K., D. Stopak, and P.Warner: Generation of spatially periodic patterns by a mechanical instability: a mechanical alternative to the Turing model. Journal of embryology and experimental morphology, 1984. 80: p. 1-20.
  • [31] Boldea, C. and C. Boboila: Pattern generation using an ultra-discrete cellular automata model for thomasmurray reaction-diffusion system, in Proceedings of the 2nd conference on European computing conference2008, World Scientific and Engineering Academy and Society (WSEAS): Malta. p. 458-462.
  • [32] Ghosh, R. and C. Tomlin: Symbolic reachable set computation of piecewise affine hybrid automata and its application to biological modeling: Delta-Notch protein signaling. IEE Transactions on Systems Biology, 2004. 1: p. 170-183.
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Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-article-BUS8-0027-0011
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