Nested sampling for parameter inference in systems biology: application to an exemplar circadian model.
Nested sampling for parameter inference in systems biology: application to an exemplar circadian model.
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DOI：
10.1186/1752-0509-7-72
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发表时间：
2013-07-30
影响因子：
--
通讯作者：
Akman OE
中科院分区：
文献类型：
--
作者：
Aitken S;Akman OE
模型选择和参数推断是系统生物学中尚未完全解决的复杂问题。与参数优化相比，参数推断计算参数均值及其标准差（或完整的后验分布），从而产生关于数据和模型拓扑约束推断参数值的程度的重要信息。我们报告应用嵌套抽样，统计方法来计算贝叶斯证据Z，推断参数，并估计日志Z在一个既定的昼夜节律模型。降解和转录参数之间的变异系数的十倍的差异被证明。我们进一步表明，剩余的参数值的不确定性减少的分析越来越多的昼夜节律周期的数据，多达4个周期，但不受采样数据更频繁。新的算法用于计算模型的可能性，和嵌套抽样算法的性能的表征也有报道。我们开发的方法大大提高了似然计算的计算效率，以及嵌套抽样中的探索性步骤。我们已经证明，在一个范例的昼夜节律模型，后参数密度的估计（总结参数均值和标准差）的影响主要是由时间序列的长度，成为更狭窄的限制，作为考虑的昼夜节律周期的数量增加。我们还展示了区分高度约束和较少约束参数的变异系数的效用。
Model selection and parameter inference are complex problems that have yet to be fully addressed in systems biology. In contrast with parameter optimisation, parameter inference computes both the parameter means and their standard deviations (or full posterior distributions), thus yielding important information on the extent to which the data and the model topology constrain the inferred parameter values. We report on the application of nested sampling, a statistical approach to computing the Bayesian evidence Z, to the inference of parameters, and the estimation of log Z in an established model of circadian rhythms. A ten-fold difference in the coefficient of variation between degradation and transcription parameters is demonstrated. We further show that the uncertainty remaining in the parameter values is reduced by the analysis of increasing numbers of circadian cycles of data, up to 4 cycles, but is unaffected by sampling the data more frequently. Novel algorithms for calculating the likelihood of a model, and a characterisation of the performance of the nested sampling algorithm are also reported. The methods we develop considerably improve the computational efficiency of the likelihood calculation, and of the exploratory step within nested sampling. We have demonstrated in an exemplar circadian model that the estimates of posterior parameter densities (as summarised by parameter means and standard deviations) are influenced predominately by the length of the time series, becoming more narrowly constrained as the number of circadian cycles considered increases. We have also shown the utility of the coefficient of variation for discriminating between highly-constrained and less-well constrained parameters.
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影响因子：
4.3
作者：
Down TA;Bergman CM;Su J;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
2.7
作者：
Chopin, Nicolas;Robert, Christian P.
通讯作者：
Robert, Christian P.
影响因子：
4.4
作者：
Gonze, D;Halloy, J;Gaspard, P
通讯作者：
Gaspard, P
影响因子：
4.5
作者：
Neal, RM
通讯作者：
Neal, RM
DOI：
10.1111/j.1365-2966.2011.18962.x
发表时间：
2011-08-01
影响因子：
4.8
作者：
Feroz, F.;Balan, S. T.;Hobson, M. P.
通讯作者：
Hobson, M. P.