Kimura Shuhei, Nakayama Satoshi, Hatakeyama Mariko
Graduate School of Engineering, Tottori University, Koyama-minami, Tottori, Japan.
Bioinformatics. 2009 Apr 1;25(7):918-25. doi: 10.1093/bioinformatics/btp072. Epub 2009 Feb 2.
Genetic network inference methods based on sets of differential equations generally require a great deal of time, as the equations must be solved many times. To reduce the computational cost, researchers have proposed other methods for inferring genetic networks by solving sets of differential equations only a few times, or even without solving them at all. When we try to obtain reasonable network models using these methods, however, we must estimate the time derivatives of the gene expression levels with great precision. In this study, we propose a new method to overcome the drawbacks of inference methods based on sets of differential equations.
Our method infers genetic networks by obtaining classifiers capable of predicting the signs of the derivatives of the gene expression levels. For this purpose, we defined a genetic network inference problem as a series of discrimination tasks, then solved the defined series of discrimination tasks with a linear programming machine. Our experimental results demonstrated that the proposed method is capable of correctly inferring genetic networks, and doing so more than 500 times faster than the other inference methods based on sets of differential equations. Next, we applied our method to actual expression data of the bacterial SOS DNA repair system. And finally, we demonstrated that our approach relates to the inference method based on the S-system model. Though our method provides no estimation of the kinetic parameters, it should be useful for researchers interested only in the network structure of a target system.
Supplementary data are available at Bioinformatics online.
基于微分方程组的遗传网络推断方法通常需要大量时间,因为方程组必须求解多次。为了降低计算成本,研究人员提出了其他方法来推断遗传网络,即只需对方程组求解几次,甚至根本无需求解。然而,当我们尝试使用这些方法获得合理的网络模型时,必须极其精确地估计基因表达水平的时间导数。在本研究中,我们提出了一种新方法来克服基于微分方程组的推断方法的缺点。
我们的方法通过获得能够预测基因表达水平导数符号的分类器来推断遗传网络。为此,我们将遗传网络推断问题定义为一系列判别任务,然后用线性规划机器解决所定义的一系列判别任务。我们的实验结果表明,所提出的方法能够正确推断遗传网络,并且比其他基于微分方程组的推断方法快500多倍。接下来,我们将我们的方法应用于细菌SOS DNA修复系统的实际表达数据。最后,我们证明了我们的方法与基于S系统模型的推断方法相关。虽然我们的方法没有对动力学参数进行估计,但它应该对只对目标系统的网络结构感兴趣的研究人员有用。
补充数据可在《生物信息学》在线获取。