Sloppy/Stiff Parameters Rankings in Sensitivity Analysis of Signaling Pathways

Malgorzata Kardynska, Jaroslaw Smieja, Anna Naumowicz, Patryk Janus, Piotr Widlak, Marek Kimmel

Abstract

Sensitivity analysis methods have been developed for over half a century. However, their application to systems biology is a relatively new concept and has not been fully investigated. In this paperwe focus on creating parameter rankings based on sloppy/stiff parameter sensitivity analysis, that can be used to find the most important parameters and processes (that have the greatest impact on the system output) and subsequently can be used to reduce the number of experiments needed to precisely estimate parameters values or to indicate molecular targets for new drugs. In order to test the proposed procedure we performed sensitivity analysis of the HSF/NF-кB pathway model - a model combining two signaling pathways essential for cell survival.

References

  1. Locke J.C.W., Southern M.M., Kozma-Bognar L., Hibberd V., Brown P.E., Turner M.S., and Millar A.J., (2005) Extension of a genetic network model by iterative experimentation and mathematical analysis, MolSystBiol 1, 0013.
  2. Voit E., Neves A.R., and Santos H. (2006) The intricate side of systems biology, PNAS 103, 9452-9457.
  3. Maerkl S.J. and Quake S.R., (2007) A systems approach to measuring the binding energy landscapes of transcription factors, Science 315, 233-237.
  4. Rand D.A., (2008) Mapping the global sensitivity of cellular network dynamics, J. Royal Society Interface 5, 59-69.
  5. Gutenkunst R.N., Watefall J.J., Casey F.P., Brown K.S., Myers C.R., and Sethna J.P., (2007) Universally sloppy parameter sensitivities in systems biology models, PLoS Computational Biology 3, 1871-1878.
  6. Kim K.A., Spencer S.L., Albeck J.G., Burke J.M., Sorger P.K., Gaudet S., and Kim H., (2010) Systematic calibration of a cell signaling network model, BMC Bioinformatics 11, 202.
  7. Marin-Sanguino A., Gupta S.K., Voit E.O., and Vera J., (2011) Biochemical pathway modeling tools for drug target detection in cancer and other complex diseases, Methods in Enzymology 487, 319-369.
  8. Smieja J., Kardynska M., Naumowicz A., Janus P., Widlak P., Kimmel M., (2015) In Silico Analysis of Interactions Between NFkB and HSF Pathways, Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms, Oscar Pastor, Christine Sinoquet, Ana Fred, Hugo Gamboa and Dirk Elias (eds.), Lisbon, Portugal, 201- 206.
  9. Cataldi A., Rapino M., Centurione L., Sabatini N., Grifone G., Garaci F., Rana R., (2003) NF-?B activation plays an antiapoptotic role in human leukemic K562 cells exposed to ionizing radiation, Journal of Cellular Biochemistry 89, 956-963.
  10. Hayden, M.S., and Ghosh, S. (2012) NF-?B, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 26, 203-234.
  11. Perkins, N.D. (2012) The diverse and complex roles of NF-?B subunits in cancer. Nat. Rev. Cancer 12, 121- 132.
  12. Janus P., Pakula-Cis M., Kalinowska-Herok M., Kashchak N., Szoltysek K., Piglowski W., Widlak W., Kimmel M., Widlak P., (2011) NF-kB signalling pathway is inhibited by heat shock independently of active transcription factor HSF1 and increased levels of inducible heat shock proteins, Genes to Cells 16, 1168-1175.
  13. Lipniacki T., Paszek P., Brasier A.R., Luxon B., Kimmel M., (2004) Mathematical model of NF-?B regulatory module, J TheorBiol 228, 195-215.
  14. Szymanska Z., Zylicz M., (2009) Mathematical modelling of heat shock protein synthesis in response to temperature change, J TheorBiol 259, 562-569.
  15. Sobol I., (2001) Global sensitivity indices for nonlinear mathematical models and their Monte Carlo estimates, MathComp Sim, 55, 271-280.
Download


Paper Citation


in Harvard Style

Kardynska M., Smieja J., Naumowicz A., Janus P., Widlak P. and Kimmel M. (2016). Sloppy/Stiff Parameters Rankings in Sensitivity Analysis of Signaling Pathways . 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 278-283. DOI: 10.5220/0005820002780283


in Bibtex Style

@conference{bioinformatics16,
author={Malgorzata Kardynska and Jaroslaw Smieja and Anna Naumowicz and Patryk Janus and Piotr Widlak and Marek Kimmel},
title={Sloppy/Stiff Parameters Rankings in Sensitivity Analysis of Signaling Pathways},
booktitle={Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2016)},
year={2016},
pages={278-283},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0005820002780283},
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 - Sloppy/Stiff Parameters Rankings in Sensitivity Analysis of Signaling Pathways
SN - 978-989-758-170-0
AU - Kardynska M.
AU - Smieja J.
AU - Naumowicz A.
AU - Janus P.
AU - Widlak P.
AU - Kimmel M.
PY - 2016
SP - 278
EP - 283
DO - 10.5220/0005820002780283