Konopka Tomasz, Rooman Marianne
BioSystems, BioModeling and BioProcesses Group, Université Libre de Bruxelles, CP165/61 Brussels, Belgium.
BMC Syst Biol. 2010 Sep 3;4:123. doi: 10.1186/1752-0509-4-123.
The determination of the right model structure describing a gene regulation network and the identification of its parameters are major goals in systems biology. The task is often hampered by the lack of relevant experimental data with sufficiently low noise level, but the subset of genes whose concentration levels exhibit an oscillatory behavior in time can readily be analyzed on the basis of their Fourier spectrum, known to turn complex signals into few relatively noise-free parameters. Such genes therefore offer opportunities of understanding gene regulation quantitatively.
Fourier analysis is applied to data on gene expression levels in mouse liver cells that oscillate according to the circadian rhythm. Several model structures in the form of linear and nonlinear differential equations are matched to the data and it is shown that although the considered models can reproduce many features of the oscillatory patterns, some can be excluded on the basis of Fourier analysis without appeal to prior knowledge of regulatory pathways. A systematic method for testing models is also proposed based on measuring the effects of variations in gene copy-number on the expression levels of coupled genes.
Fourier analysis is a technique that is well-adapted to the study of biological oscillators and can be used instead or in addition to conventional modeling techniques. Its usefulness will increase as more high-resolution data become available.
确定描述基因调控网络的正确模型结构及其参数识别是系统生物学的主要目标。由于缺乏足够低噪声水平的相关实验数据，该任务常常受阻，但浓度水平随时间呈现振荡行为的基因子集可以基于其傅里叶频谱进行分析，已知傅里叶频谱能将复杂信号转化为少数相对无噪声的参数。因此，这类基因提供了定量理解基因调控的机会。
将傅里叶分析应用于小鼠肝细胞中按昼夜节律振荡的基因表达水平数据。将几种线性和非线性微分方程形式的模型结构与数据进行匹配，结果表明，尽管所考虑的模型能够重现振荡模式的许多特征，但基于傅里叶分析可以排除一些模型，而无需借助调控途径的先验知识。还提出了一种基于测量基因拷贝数变化对耦合基因表达水平影响的系统模型测试方法。
傅里叶分析是一种非常适合研究生物振荡器的技术，可以替代传统建模技术或与之结合使用。随着更多高分辨率数据的可得，其用途将会增加。
