Chen Kuang-Chi, Wang Tse-Yi, Tseng Huei-Hun, Huang Chi-Ying F, Kao Cheng-Yan
Division of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan.
Bioinformatics. 2005 Jun 15;21(12):2883-90. doi: 10.1093/bioinformatics/bti415. Epub 2005 Mar 31.
The explosion of microarray studies has promised to shed light on the temporal expression patterns of thousands of genes simultaneously. However, available methods are far from adequate in efficiently extracting useful information to aid in a greater understanding of transcriptional regulatory network. Biological systems have been modeled as dynamic systems for a long history, such as genetic networks and cell regulatory network. This study evaluated if the stochastic differential equation (SDE), which is prominent for modeling dynamic diffusion process originating from the irregular Brownian motion, can be applied in modeling the transcriptional regulatory network in Saccharomyces cerevisiae.
To model the time-continuous gene-expression datasets, a model of SDE is applied to depict irregular patterns. Our goal is to fit a generalized linear model by combining putative regulators to estimate the transcriptional pattern of a target gene. Goodness-of-fit is evaluated by log-likelihood and Akaike Information Criterion. Moreover, estimations of the contribution of regulators and inference of transcriptional pattern are implemented by statistical approaches. Our SDE model is basic but the test results agree well with the observed dynamic expression patterns. It implies that advanced SDE model might be perfectly suited to portray transcriptional regulatory networks.
The R code is available on request.
微阵列研究的激增有望同时揭示数千个基因的时间表达模式。然而,现有的方法在有效提取有用信息以帮助更好地理解转录调控网络方面还远远不够。长期以来,生物系统一直被建模为动态系统,如基因网络和细胞调控网络。本研究评估了以模拟源于不规则布朗运动的动态扩散过程而闻名的随机微分方程(SDE)是否可用于对酿酒酵母中的转录调控网络进行建模。
为了对时间连续的基因表达数据集进行建模,应用了一个SDE模型来描述不规则模式。我们的目标是通过组合假定的调节因子来拟合一个广义线性模型,以估计目标基因的转录模式。通过对数似然和赤池信息准则来评估拟合优度。此外,通过统计方法实现对调节因子贡献的估计和转录模式的推断。我们的SDE模型很基础,但测试结果与观察到的动态表达模式非常吻合。这意味着先进的SDE模型可能非常适合描绘转录调控网络。
如有需要可提供R代码。