Quantitative modeling of the saccharomyces cerevisiae FLR1 regulatory network using an s-system formalism

Dulce CalÇada, Susana Vinga, Ana T. Freitas, Arlindo L. Oliveira

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In this study we address the problem of finding a quantitative mathematical model for the genetic network regulating the stress response of the yeast Saccharomyces cerevisiae to the agricultural fungicide mancozeb. An S-system formalism was used to model the interactions of a five-gene network encoding four transcription factors (Yap1, Yrr1, Rpn4 and Pdr3) regulating the transcriptional activation of the FLR1 gene. Parameter estimation was accomplished by decoupling the resulting system of nonlinear ordinary differential equations into a larger nonlinear algebraic system, and using the LevenbergMarquardt algorithm to fit the models predictions to experimental data. The introduction of constraints in the model, related to the putative topology of the network, was explored. The results show that forcing the network connectivity to adhere to this topology did not lead to better results than the ones obtained using an unrestricted network topology. Overall, the modeling approach obtained partial success when trained on the nonmutant datasets, although further work is required if one wishes to obtain more accurate prediction of the time courses.

Original languageEnglish
Pages (from-to)613-630
Number of pages18
JournalJournal Of Bioinformatics And Computational Biology
Volume9
Issue number5
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Gene Regulatory Networks
Yeast
Transcriptional Activation
Saccharomyces cerevisiae
Transcription Factors
Theoretical Models
Yeasts
Topology
Genes
Fungicides
Transcription factors
Ordinary differential equations
Parameter estimation
Nonlinear systems
Chemical activation
Mathematical models
Datasets
mancozeb

Keywords

  • FLR1 regulatory network
  • Gene regulatory network
  • S-systems

Cite this

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title = "Quantitative modeling of the saccharomyces cerevisiae FLR1 regulatory network using an s-system formalism",
abstract = "In this study we address the problem of finding a quantitative mathematical model for the genetic network regulating the stress response of the yeast Saccharomyces cerevisiae to the agricultural fungicide mancozeb. An S-system formalism was used to model the interactions of a five-gene network encoding four transcription factors (Yap1, Yrr1, Rpn4 and Pdr3) regulating the transcriptional activation of the FLR1 gene. Parameter estimation was accomplished by decoupling the resulting system of nonlinear ordinary differential equations into a larger nonlinear algebraic system, and using the LevenbergMarquardt algorithm to fit the models predictions to experimental data. The introduction of constraints in the model, related to the putative topology of the network, was explored. The results show that forcing the network connectivity to adhere to this topology did not lead to better results than the ones obtained using an unrestricted network topology. Overall, the modeling approach obtained partial success when trained on the nonmutant datasets, although further work is required if one wishes to obtain more accurate prediction of the time courses.",
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Quantitative modeling of the saccharomyces cerevisiae FLR1 regulatory network using an s-system formalism. / CalÇada, Dulce; Vinga, Susana; Freitas, Ana T.; Oliveira, Arlindo L.

In: Journal Of Bioinformatics And Computational Biology, Vol. 9, No. 5, 10.2011, p. 613-630.

Research output: Contribution to journalArticle

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