Parameter estimation and determinability analysis applied to Drosophila gap gene circuits
Parameter estimation and determinability analysis applied to Drosophila gap gene circuits
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DOI：
10.1186/1752-0509-2-83
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发表时间：
2008-09-25
影响因子：
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通讯作者：
Blom, Joke G.
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文献类型：
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作者：
Ashyraliyev, Maksat;Jaeger, Johannes;Blom, Joke G.
背景：真实过程的数学建模通常需要估计未知参数。一旦通过优化方法找到了参数，就必须评估参数估计的质量，特别是在使用参数值从模型中得出生物学结论的情况下。我们应用我们的方法评估了果蝇早期胚胎GAP基因网络的基因回路模型的参数可测性。结论：我们的分析表明，由于参数之间的相关性，所考虑的模型的参数都不能以合理的精度单独确定。因此，该模型不能用作推断定量监管权重的工具。另一方面，我们的结果表明，仍然有可能对基因网络的调控拓扑得出可靠的定性结论。此外，它改进了以前对同一模型的分析，使我们能够确定哪些定性结论是可靠的，哪些是不明确的。
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.