Temporal Logic based Framework to Model and Analyse Gene Networks with Alternative Splicing
Sohei Ito
2016
Abstract
Toward system-level understanding of biological systems, we need a formalism to model and analyse them. Due to incompleteness of knowledge about quantitative parameters and molecular mechanisms, qualitative methods have been useful alternatives. We have been working on temporal logic-based approach for qualitative modelling and analysis of gene regulatory networks. Although our framework is well-established to model several aspects of gene regulation, we still lack treatment of alternative splicing, which contributes to proteomic diversity of eukaryotic organisms. In this paper we extend our logic-based qualitative framework to be able to capture alternative splicing, which is crucial to model the gene regulatory networks in eukaryotic organisms. We study mechanisms of alternative splicing and propose how we model each mechanism, then demonstrate the modelling method by analysing the regulatory network of sex determination in Drosophila and verify that the network ensures sex determination.
References
- Aoshima, T. (2003). On a verification System for Reactive System Specifications. PhD thesis, Tokyo Institute of Technology.
- Batt, G., Salah, R. B., and Maler, O. (2007). On timed models of gene networks. In FORMATS 2007, volume 4763 of LNCS, pages 38-52.
- Camara, N., Whitworth, C., and Van Doren, M. (2008). The creation of sexual dimorphism in the Drosophila soma. Curr. Top. Dev. Biol., 83:65-107.
- Ciocchetta, F. and Hillston, J. (2009). Bio-PEPA: A framework for the modelling and analysis of biological systems. Theor. Comput. Sci., 410:3065-3084.
- David, C. and Manley, J. (2008). The search for alternative splicing regulators: new approaches offer a path to a splicing code. Genes Dev., 22(3):279-285.
- Fear, J., Arbeitman, M. N., Salomon, M., Dalton, J., Tower, J., Nuzhdin, S. V., and McIntyre, L. M. (2015). The wright stuff: reimagining path analysis reveals novel components of the sex determination hierarchy in drosophila melanogaster. BMC Systems Biology, 9:53.
- Heiner, M., Gilbert, D. R., and Donaldson, R. (2008). Petri nets for systems and synthetic biology. In SFM 2008, volume 5016 of LNCS, pages 215-264.
- Hertel, K. (2008). Combinatorial control of exon recognition. J. Biol. Chem., 283(3):1211-1215.
- Ito, S., Hagihara, S., and Yonezaki, N. (2014). A qualitative framework for analysing homeostasis in gene networks. In Proceedings of BIOINFORMATICS 2014, pages 5-16.
- Ito, S., Ichinose, T., Shimakawa, M., Izumi, N., Hagihara, S., and Yonezaki, N. (2013a). Modular analysis of gene networks by linear temporal logic. J. Integrative Bioinformatics, 10(2).
- Ito, S., Ichinose, T., Shimakawa, M., Izumi, N., Hagihara, S., and Yonezaki, N. (2013b). Qualitative analysis of gene regulatory networks using network motifs. In Proceedings of BIOINFORMATICS 2013, pages 15- 24.
- Ito, S., Ichinose, T., Shimakawa, M., Izumi, N., Hagihara, S., and Yonezaki, N. (2015). Qualitative analysis of gene regulatory networks by temporal logic. Theor. Comput. Sci., 594(23):151-179.
- 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 BIBE 2010, pages 232-237.
- Kornblihtt, A. (2005). Promoter usage and alternative splicing. Curr. Opin. Cell Biol., 17(3):262-268.
- Louis, M., Holm, L., Sánchez, L., and Kaufman, M. (2003). A theoretical model for the regulation of sex-lethal, a gene that controls sex determination and dosage compensation in drosophila melanogaster. Genetics, 165(3):1355-84.
- Matlin, A., Clark, F., and Smith, C. (2005). Understanding alternative splicing: towards a cellular code. Nat. Rev. Mol. Cell Biol., 6(5):386-398.
- Palsson, B. (2000). The challenges of in silico biology. Nat. Biotechnol., 18:1147-50.
- Salz, H. K. and Erickson, J. W. (2010). Sex determination in Drosophila: The view from the top. Fly, 4:60-70.
- Thomas, R. (1991). Regulatory networks seen as asynchronous automata: A logical description. J. Theor. Biol., 153(1):1-23.
- Tsay, Y.-K., Chen, Y.-F., Tsai, M.-H., Wu, K.-N., and Chan, W.-C. (2007). GOAL: a graphical tool for manipulating Büchi automata and temporal formulae. In Proceedings of the 13th international conference on Tools and algorithms for the construction and analysis of systems, volume 4424 of TACAS'07, pages 466-471, Berlin, Heidelberg. Springer-Verlag.
- Vardi, M. Y. and Wolper, P. (1994). Reasoning about infinite computations. Inf. Comput., 115:1-37.
- Wen, J. (2013). Computational modeling and inference of alternative splicing regulation. PhD thesis, University of Miami.
Paper Citation
in Harvard Style
Ito S. (2016). Temporal Logic based Framework to Model and Analyse Gene Networks with Alternative Splicing . In Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2016) ISBN 978-989-758-170-0, pages 151-158. DOI: 10.5220/0005655001510158
in Bibtex Style
@conference{bioinformatics16,
author={Sohei Ito},
title={Temporal Logic based Framework to Model and Analyse Gene Networks with Alternative Splicing},
booktitle={Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2016)},
year={2016},
pages={151-158},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0005655001510158},
isbn={978-989-758-170-0},
}
in EndNote Style
TY - CONF
JO - Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2016)
TI - Temporal Logic based Framework to Model and Analyse Gene Networks with Alternative Splicing
SN - 978-989-758-170-0
AU - Ito S.
PY - 2016
SP - 151
EP - 158
DO - 10.5220/0005655001510158