Multi-scale genetic dynamic modelling I : an algorithm to compute generators | Theory in Biosciences Skip to main content
Log in

Multi-scale genetic dynamic modelling I : an algorithm to compute generators

  • Published:
Theory in Biosciences Aims and scope Submit manuscript

Abstract

We present a new approach or framework to model dynamic regulatory genetic activity. The framework is using a multi-scale analysis based upon generic assumptions on the relative time scales attached to the different transitions of molecular states defining the genetic system. At micro-level such systems are regulated by the interaction of two kinds of molecular players: macro-molecules like DNA or polymerases, and smaller molecules acting as transcription factors. The proposed genetic model then represents the larger less abundant molecules with a finite discrete state space, for example describing different conformations of these molecules. This is in contrast to the representations of the transcription factors which are—like in classical reaction kinetics—represented by their particle number only. We illustrate the method by considering the genetic activity associated to certain configurations of interacting genes that are fundamental to modelling (synthetic) genetic clocks. A largely unknown question is how different molecular details incorporated via this more realistic modelling approach lead to different macroscopic regulatory genetic models which dynamical behaviour might—in general—be different for different model choices. The theory will be applied to a real synthetic clock in a second accompanying article (Kirkilionis et al., Theory Biosci, 2011).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
¥17,985 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Japan)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Arvas M et al (2010) Detecting novel genes with sparse arrays. Gene 467(1–2):41–51. doi:10.1016/j.gene.2010.07.009

    Article  PubMed  CAS  Google Scholar 

  • Atkinson MR et al (2003) Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli. Cell 113(5):597–607

    Article  PubMed  CAS  Google Scholar 

  • Battle A et al (2010) Automated identification of pathways from quantitative genetic interaction data. Mol Syst Biol 6:379. doi:10.1038/msb.2010.27

    Article  PubMed  Google Scholar 

  • Blasberg R (2002) PET imaging of gene expression. Eur J Cancer 38(16):2137–2146

    Article  PubMed  CAS  Google Scholar 

  • Bockhorst J et al (2003) A Bayesian network approach to operon prediction. Bioinformatics 19(10):1227–1235

    Article  PubMed  CAS  Google Scholar 

  • Branicky MS (2005) Introduction to hybrid systems. In: Hristu-Varsakelis D, Levine WS (eds) Handbook of networked and embedded control systems. Birkhäuser, Boston, pp 91–116

  • Broom BM et al (2010) Building networks with microarray data. Methods Mol Biol 620:315–343. doi:10.1007/978-1-60761-580-4_10

    Article  PubMed  CAS  Google Scholar 

  • Cantone I et al (2009) A yeast synthetic network for in vivo assessment of reverse-engineering and modeling approaches. Cell 137(1):172–181. doi:10.1016/j.cell.2009.01.055

    Article  PubMed  CAS  Google Scholar 

  • Domijan M, Kirkilionis M (2008) Graph theory and qualitative analysis of reaction networks. Netw Heterog Media 3(2):295–322

    Article  Google Scholar 

  • Domijan M, Kirkilionis M (2009) Bistability and oscillations in chemical reaction networks. J Math Biol 59(4):467–501. doi:10.1007/s00285-008-0234-7

    Article  PubMed  Google Scholar 

  • Dufva M (2009) Introduction to microarray technology. Methods Mol Biol 529:1–22. doi:10.1007/978-1-59745-538-1_1

    Article  PubMed  CAS  Google Scholar 

  • Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403(6767):335–338

    Article  PubMed  CAS  Google Scholar 

  • Fromentin J, Eveillard D, Roux O (2010) Hybrid modeling of biological networks: mixing temporal and qualitative biological properties. BMC Syst Biol 4:79. doi:10.1186/1752-0509-4-79

    Article  PubMed  Google Scholar 

  • Fuellen G (2010) Evolution of gene regulation—on the road towards computational inferences. Brief Bioinform. doi:10.1093/bib/bbq060

  • Galperin MY, Koonin EV (2010) From complete genome sequence to complete understanding?. Trends Biotechnol 28(8):398–406. doi:10.1016/j.tibtech.2010.05.006

    Article  PubMed  CAS  Google Scholar 

  • Gardiner CW (1990) Handbook of stochastic methods. Springer Verlag, Berlin

    Google Scholar 

  • Gardner TS, Cantor CR, Collins JJ (2000) Construction of a genetic toggle switch in Escherichia coli. Nature 403(6767):339–342

    Article  PubMed  CAS  Google Scholar 

  • Gillespie DT (2007) Stochastic simulation of chemical kinetics. Annu Rev Phys Chem 58:35–55

    Article  PubMed  CAS  Google Scholar 

  • Gonze D (2010) Coupling oscillations and switches in genetic networks. Biosystems 99(1):60–69. doi:10.1016/j.biosystems.2009.08.009

    Article  PubMed  Google Scholar 

  • Guantes R, Poyatos JF (2006) Dynamical principles of two-component genetic oscillators. PLoS Comput Biol 2(3):e30

    Article  PubMed  Google Scholar 

  • Hamilton JD (1994) Time series analysis. Princeton University Press, Princeton

  • Hartemink AJ et al (2001) Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks. In: Pacific symposium on biocomputing, pp 422–433

  • Hasty J, McMillen D, Collins JJ (2002) Engineered gene circuits. Nature 420(6912):224–230

    Article  PubMed  CAS  Google Scholar 

  • Holmans P (2010) Statistical methods for pathway analysis of genome-wide data for association with complex genetic traits. Adv Genet 72:141–179. doi:10.1016/B978-0-12-380862-2.00007-2

    Article  PubMed  Google Scholar 

  • Jacob F, Monod J (1961) On the regulation of gene activity. In: Cold Spring Harbour symposia on quantitative biology 26:193–211

  • Jaimovich A et al (2010) Modularity and directionality in genetic interaction maps. Bioinformatics 26(12):i228–i236. doi:10.1093/bioinformatics/btq197

    Article  PubMed  CAS  Google Scholar 

  • Jansen R et al (2003) A Bayesian networks approach for predicting protein-protein interactions from genomic data. Science 302(5644):449–453. doi:10.1126/science.1087361

    Article  PubMed  CAS  Google Scholar 

  • Janus U (2009) Biochemical systems analysis: a study of function and design in molecular biology. Ph.D thesis, University of Warwick

  • Janus U (2009) A PERL Algorithm to compute infinitesimal generators for Markov chains describing genetic modules, University of Warwick. Download from: http://lora.maths.warwick.ac.uk

  • Joosten RP et al (2010) A series of PDB related databases for everyday needs. Nucleic Acids Res. doi:10.1093/nar/gkq1105

  • Julius AA et al (2007) Hybrid model predictive control of induction of Escherichia coli. In: Proceedings of the 46th IEEE conference on decision and control. New Orleans, LA, USA, Dec. 12–14

  • Kepler TB, Elston TC (2001) Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations. Biophys J 81(6):3116–3136

    Article  PubMed  CAS  Google Scholar 

  • Kirkilionis M (2010) Exploration of cellular reaction systems. Brief Bioinform 11(1):153–178

    Article  PubMed  Google Scholar 

  • Kirkilionis M, Sbano L (2010) An averaging principle for combined interaction graphs. Connectivity and applications to genetic switches. Adv Complex Syst 13(3):293–326

    Article  Google Scholar 

  • Kirkilionis M, Sbano L (In preparation) An averaging principle for combined interaction graphs. Adv Complex Syst

  • Kirkilionis M, Janus U, Sbano L (2011) Multi-scale genetic dynamic modelling II: application to synthetic biology. An algorithmic markov chain based approach. Theory Biosci. doi:10.1007/s12064-011-0126-z

  • Madar A, Bonneau R (2009) Learning global models of transcriptional regulatory networks from data. Methods Mol Biol 541:181. doi:10.1007/978-1-59745-243-4_9

    Article  PubMed  CAS  Google Scholar 

  • Mader U et al (2010) Comprehensive identification and quantification of microbial transcriptomes by genome-wide unbiased methods. Curr Opin Biotechnol. doi:10.1016/j.copbio.2010.10.003

  • Marucci L et al (2010) Derivation, identification and validation of a computational model of a novel synthetic regulatory network in yeast. J Math Biol. doi:10.1007/s00285-010-0350-z

  • Merris R (1997) Multilinear algebra. Gordon and Beach Science Publishers, Amsterdam

  • Ng PC, Kirkness EF (2010) Whole genome sequencing. Methods Mol Biol 628:215–226. doi:10.1007/978-1-60327-367-1_12

    Article  PubMed  CAS  Google Scholar 

  • Ritchie MD, Bush WS (2010) Genome simulation approaches for synthesizing in silico datasets for human genomics. Adv Genet 72:1–24. doi:10.1016/B978-0-12-380862-2.00001-1

    Article  PubMed  CAS  Google Scholar 

  • Sarder P et al (2010) Estimating sparse gene regulatory networks using a bayesian linear regression. IEEE Trans Nanobiosci 9(2):21–131. doi:10.1109/TNB.2010.2043444

    Article  Google Scholar 

  • Sbano L, Kirkilionis M (2008a) Molecular systems with infinite and finite degrees of freedom. Part I: multi-scale analysis. WMI Preprint 5/2007. Available at: arXiv:0802.4259v2 [q-bio.BM]

  • Sbano L, Kirkilionis M (2008b) Molecular systems with infinite and finite degrees of freedom. Part II: Deterministic dynamics and examples. WMI Preprint 7/2007. Available at: arXiv:0802.4279v1 [q-bio.MN]

  • Sbano L, Kirkilionis M (2008c) Multiscale analysis of reaction networks. Theory Biosci 127:107–123

    Article  PubMed  Google Scholar 

  • Schatz MC (2010) The missing graphical user interface for genomics. Genome Biol 11(8):128. doi:10.1186/gb-2010-11-8-128

    Article  PubMed  Google Scholar 

  • Serganova I et al (2008) Molecular imaging: reporter gene imaging. Handb Exp Pharmacol 185(Pt 2):167–223. doi:10.1007/978-3-540-77496-9_8

    Article  PubMed  CAS  Google Scholar 

  • Shmulevich I, Aitchison JD (2009) Deterministic and stochastic models of genetic regulatory networks. Methods Enzymol 46:335–356. doi:10.1016/S0076-6879(09)67013-0

    Article  Google Scholar 

  • van Kampen NG (1992) Stochastic processes in physics and chemistry. Elsevier B.V., Amsterdam

  • Vilar JMG, Leibler S (2003) DNA looping and physical constraints on transcription regulation. J Mol Biol 331(5):981–989

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study in this article was partially supported by UniNet contract 12990 funded by the European Commission in the context of the VI Framework Programme.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Markus Kirkilionis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirkilionis, M., Janus, U. & Sbano, L. Multi-scale genetic dynamic modelling I : an algorithm to compute generators. Theory Biosci. 130, 165–182 (2011). https://doi.org/10.1007/s12064-011-0125-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12064-011-0125-0

Keywords

Navigation