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Regulatory Networks

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Computational Toxicology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 930))

Abstract

The usefulness of mathematical models for the biological regulatory networks relies on the predictive capability of the models in order to suggest interesting hypotheses and suitable biological experiments. All mathematical frameworks dedicated to biological regulatory networks must manage a large number of abstract parameters, which are not directly measurable in the cell. The cornerstone to establish predictive models is the identification of the possible parameter values. Formal frameworks involve qualitative models with discrete values and computer-aided logic reasoning. They can provide the biologists with an automatic identification of the parameters via a formalization of some biological knowledge into temporal logic formulas. For pedagogical reasons, we focus on gene regulatory networks and develop a qualitative model of the detoxification of benzo[a]pyrene in human cells to illustrate the approach.

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References

  1. Kier LB, Bonchev D, Buck GA (2005) Modeling biochemical networks: a cellular-automata approach. Chem Biodivers 2:233–243

    Article  PubMed  Google Scholar 

  2. Hoehme S, Drasdo D (2010) A cell-based simulation software for multicellular systems. Bioinformatics 26(20):2641–2642

    Article  PubMed  CAS  Google Scholar 

  3. Poudret M, Comet J-P, Le Gall P et al (2008) Topology-based abstraction of complex biological systems: application to the Golgi apparatus. Theory Biosci 127:79–88

    Article  PubMed  Google Scholar 

  4. Eungdamrong NJ, Iyengar R (2004) Modeling cell signaling networks. Biol Cell 96:355–362

    PubMed  CAS  Google Scholar 

  5. Schuster S, Hilgetag C, Woods JH et al (2002) Elementary flux modes in biochemical reaction systems: algebraic properties, validated calculation procedure and example from nucleotide metabolism. J Math Biol 45:153–181

    Article  PubMed  CAS  Google Scholar 

  6. Thomas R, d’Ari R (1990) Biological feedback. CRC, Boca Raton

    Google Scholar 

  7. Bostrom CE, Gerde P, Hanberg A et al (2002) Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambiant air. Environ Health Perspect 110(suppl 3):451–488

    Article  PubMed  CAS  Google Scholar 

  8. Phillips DH (1999) Polycyclic aromatic hydrocarbons in the diet. Mutat Res 443(1–2):39–147

    Google Scholar 

  9. Schmidt JV, Bradfield CA (1996) Ah receptor signaling pathways. Annu Rev Cell Dev Biol 12:55–89

    Article  PubMed  CAS  Google Scholar 

  10. Hankinson O (1995) The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 35:307–340

    Article  PubMed  CAS  Google Scholar 

  11. Gu YZ, Hogenesch JB, Bradfield CA (2000) The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol 40:519–561

    Article  PubMed  CAS  Google Scholar 

  12. Nebert DW, Roe AL, Dieter MZ et al (2000) Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. Biochem Pharmacol 59:65–85

    Article  PubMed  CAS  Google Scholar 

  13. Nebert DW, Dalton TP, Okey AB et al (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 279(23):23847–23850

    Article  PubMed  CAS  Google Scholar 

  14. Nebert DW, Vasiliou V (2004) Analysis of the glutathione S-transferase (GST) gene family. Hum Genomics 1(6):460–464

    PubMed  CAS  Google Scholar 

  15. Nioi P, Hayes JD (2004) Contribution of NAD(P)H:quinine oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix–loop–helix transcription factors. Mutat Res 555(1–2):149–171

    PubMed  CAS  Google Scholar 

  16. Yoshinari K, Okino N, Sato T et al (2006) Induction of detoxifying enzymes in rodent white adipose tissue by aryl hydrocarbon receptor agonists and antioxidants. Drug Metab Dispos 4:1081–1089

    Article  Google Scholar 

  17. Wills LP, Zhu S, Willett KL et al (2009) Effect of CYP1A inhibition on the biotransformation of benzo[a]pyrene in two populations of Fundulus heteroclitus with different exposure histories. Aquat Toxicol 92(3):195–201

    Article  PubMed  CAS  Google Scholar 

  18. Parkinson A (1996) Biotransformation of xenobiotics. In: Klaassen CD (ed) Casarett and Doull’s toxicology: the basic science of poisons. McGraw-Hill, New York

    Google Scholar 

  19. Yang SK (1988) Stereoselectivity of cytochrome P-450 isozyemes and epoxide hydrolase in the metabolism of polycylic aromatic hydrocarbons. Biochem Pharmocol 37:61–70

    Article  CAS  Google Scholar 

  20. Köhle C, Bock KW (2007) Coordinate regulation of phase I and II xenobiotic metabolism by the Ah receptor and Nrf2. Biochem Pharmacol 73:1853–1862

    Article  PubMed  Google Scholar 

  21. de Jong H (2002) Modeling and simulation of genetic regulatory systems: a literature review. J Comput Biol 9(1):67–103

    Article  PubMed  Google Scholar 

  22. Gillespie DT (1977) Exact stochastic simulation of coupled chemical reactions. J Phys Chem 81:2340–2361

    Article  CAS  Google Scholar 

  23. Tyson JJ, Othmer HG (1978) The dynamics of feedback control circuits in biochemical pathways. Prog Theor Biol 5:1–62

    CAS  Google Scholar 

  24. Bernot G, Comet J-P, Richard A et al (2004) Application of formal methods to biological regulatory networks: extending Thomas’ asynchronous logical approach with temporal logic. J Theor Biol 229(3):339–347

    Article  PubMed  Google Scholar 

  25. Khalis Z, Comet J-P, Richard A et al (2009) The SMBioNet method for discovering models of gene regulatory networks. Genes Genomes Genomics 3(special issue 1):15–22

    Google Scholar 

  26. Emerson EA (1990) Temporal and modal logic. In: Van Leeuwen J (ed) Handbook of theoretical computer science. MIT Press, Cambridge

    Google Scholar 

  27. Cimatti A, Clarke EM, Giunciglia EF et al (2002) NuSMV 2: An open source tool for symbolic model checking. In: Proceeding of international conference on computer-aided verification (CAV 2002), pp 27–31

    Google Scholar 

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Correspondence to Gilles Bernot .

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Bernot, G., Comet, JP., Faverney, C.Rd. (2013). Regulatory Networks. In: Reisfeld, B., Mayeno, A. (eds) Computational Toxicology. Methods in Molecular Biology, vol 930. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-059-5_9

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  • DOI: https://doi.org/10.1007/978-1-62703-059-5_9

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-058-8

  • Online ISBN: 978-1-62703-059-5

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