Qualitative Analysis of Gene Regulatory Networks using Network Motifs

Sohei Ito, Takuma Ichinose, Masaya Shimakawa, Naoko Izumi, Shigeki Hagihara, Naoki Yonezaki

2013

Abstract

We developed a method for analysing gene regulatory networks in a purely qualitative fashion. Behaviours of networks are captured as transition systems using propositions for gene states (ON or OFF), and those related to threshold values for gene activation/inhibition. Possible behaviours of networks are specified by logical formulae in Linear Temporal Logic (LTL). With this specification, it is possible to check whether some/all behaviours satisfy a biological property, which is difficult for quantitative analyses like an ordinary differential equation approach. Our method uses satisfiability checking of LTL. Due to the complexity of LTL satisfiability checking, analyses of large networks are generally intractable in this method. To tackle this issue, in this paper, we propose approximate analysis method in which we specify behaviours in simpler formulae which compress/expand the possible behaviours of networks. We present approximate specifications for some network patterns called network motifs.

References

  1. Alon, U. (2007). Network motifs: theory and experimental approaches. Nature reviews. Genetics, 8(6):450-461.
  2. Aoshima, T., Sakuma, K., and Yonezaki, N. (2001). An efficient verification procedure supporting evolution of reactive system specifications. In Proceedings of the 4th International Workshop on Principles of Software Evolution, IWPSE 7801, pages 182-185, New York, NY, USA. ACM.
  3. Bernot, G., Comet, J., Richard, A., and Guespin, J. (2004). Application of formal methods to biological regulatory networks: extending Thomas' asynchronous logical approach with temporal logic. J. Theor. Biol., 229(3):339-347.
  4. de Jong, H., Geiselmann, J., Hernandez, G., and Page, M. (2003). Genetic network analyzer: Qualitative simulation of genetic regulatory networks. Bioinformatics, 19(3):336-344.
  5. Fages, F., Soliman, S., and Chabrier-Rivier, N. (2004). Modelling and querying interaction networks in the biochemical abstract machine BIOCHAM. Journal of Biological Physics and Chemistry, 4:64-73.
  6. Govan, J. R. W. and Harris, G. S. (1986). Pseudomonas aeruginosa and cystic fibrosis: unusual bacterial adaptation and pathogenesis. Microbiological Sciences, 3(10):302-308.
  7. Guespin, J. and Kauffman, M. (2001). Positive feedback circuits and adaptive regulations in bacteria. Acta biotheoretica, 49(4):207-218.
  8. Ito, S., Izumi, N., Hagihara, S., and Yonezaki, N. (2010). Qualitative analysis of gene regulatory networks by satisfiability checking of linear temporal logic. In Proceedings of the 10th IEEE International Conference on Bioinformatics & Bioengineering, pages 232-237.
  9. Schurr, M. J., Martin, D. W., Mudd, M. H., and Deretic, V. (1994). Gene cluster controlling conversion to alginate-overproducing phenotype in Pseudomonas aeruginosa: functional analysis in a heterologous host and role in the instability of mucoidy. Journal of Bacteriology, 176:3375-3382.
  10. Sistla, A. P. and Clarke, E. M. (1985). The complexity of propositional linear temporal logics. J. ACM, 32:733- 749.
  11. Snoussi, E. and Thomas, R. (1993). Logical identification of all steady states: the concept of feedback loop characteristic states. Bulletin of Mathematical Biology, 55(5):973-991.
  12. Thomas, R. and Kauffman, M. (2001). Multistationarity, the basis of cell differentiation and memory. II. logical analysis of regulatory networks in terms of feedback circuits. Chaos: An Interdisciplinary Journal of Nonlinear Science, 11(1):180-195.
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Paper Citation


in Harvard Style

Ito S., Ichinose T., Shimakawa M., Izumi N., Hagihara S. and Yonezaki N. (2013). Qualitative Analysis of Gene Regulatory Networks using Network Motifs . In Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2013) ISBN 978-989-8565-35-8, pages 15-24. DOI: 10.5220/0004188400150024


in Bibtex Style

@conference{bioinformatics13,
author={Sohei Ito and Takuma Ichinose and Masaya Shimakawa and Naoko Izumi and Shigeki Hagihara and Naoki Yonezaki},
title={Qualitative Analysis of Gene Regulatory Networks using Network Motifs},
booktitle={Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2013)},
year={2013},
pages={15-24},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0004188400150024},
isbn={978-989-8565-35-8},
}


in EndNote Style

TY - CONF
JO - Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2013)
TI - Qualitative Analysis of Gene Regulatory Networks using Network Motifs
SN - 978-989-8565-35-8
AU - Ito S.
AU - Ichinose T.
AU - Shimakawa M.
AU - Izumi N.
AU - Hagihara S.
AU - Yonezaki N.
PY - 2013
SP - 15
EP - 24
DO - 10.5220/0004188400150024