Gustafsson Mika, Hörnquist Michael, Lundström Jesper, Björkegren Johan, Tegnér Jesper
Department of Science and Technology, Linköping University, Norrköping, Sweden.
Ann N Y Acad Sci. 2009 Mar;1158:265-75. doi: 10.1111/j.1749-6632.2008.03764.x.
The quest to determine cause from effect is often referred to as reverse engineering in the context of cellular networks. Here we propose and evaluate an algorithm for reverse engineering a gene regulatory network from time-series and steady-state data. Our algorithmic pipeline, which is rather standard in its parts but not in its integrative composition, combines ordinary differential equations, parameter estimations by least angle regression, and cross-validation procedures for determining the in-degrees and selection of nonlinear transfer functions. The result of the algorithm is a complete directed network, in which each edge has been assigned a score from a bootstrap procedure. To evaluate the performance, we submitted the outcome of the algorithm to the reverse engineering assessment competition DREAM2, where we used the data corresponding to the InSilico1 and InSilico2 networks as input. Our algorithm outperformed all other algorithms when inferring one of the directed gene-to-gene networks.
在细胞网络的背景下,从结果确定原因的探索通常被称为逆向工程。在此,我们提出并评估一种用于从时间序列和稳态数据逆向工程基因调控网络的算法。我们的算法流程,其各个部分相当标准,但整体组合并非如此,它结合常微分方程、通过最小角回归进行参数估计以及用于确定入度和选择非线性传递函数的交叉验证程序。该算法的结果是一个完整的有向网络,其中每条边都通过自展程序被赋予了一个分数。为了评估性能,我们将算法的结果提交到逆向工程评估竞赛DREAM2,在那里我们使用与InSilico1和InSilico2网络相对应的数据作为输入。在推断有向基因到基因网络之一时,我们的算法优于所有其他算法。