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Parameter estimation and determinability analysis applied to Drosophila gap gene circuits.


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Authors

Ashyraliyev, Maksat 
Jaeger, Johannes 
Blom, Joke G 

Abstract

BACKGROUND: Mathematical modeling of real-life processes often requires the estimation of unknown parameters. Once the parameters are found by means of optimization, it is important to assess the quality of the parameter estimates, especially if parameter values are used to draw biological conclusions from the model. RESULTS: In this paper we describe how the quality of parameter estimates can be analyzed. We apply our methodology to assess parameter determinability for gene circuit models of the gap gene network in early Drosophila embryos. CONCLUSION: Our analysis shows that none of the parameters of the considered model can be determined individually with reasonable accuracy due to correlations between parameters. Therefore, the model cannot be used as a tool to infer quantitative regulatory weights. On the other hand, our results show that it is still possible to draw reliable qualitative conclusions on the regulatory topology of the gene network. Moreover, it improves previous analyses of the same model by allowing us to identify those interactions for which qualitative conclusions are reliable, and those for which they are ambiguous.

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RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.

Keywords

Animals, Drosophila, Gene Regulatory Networks, Genes, Insect, Models, Genetic

Journal Title

BMC Syst Biol

Conference Name

Journal ISSN

1752-0509
1752-0509

Volume Title

Publisher

Springer Science and Business Media LLC