Unravelling gene networks from noisy under-determined experimental perturbation data.

A de la Fuente, D P Makhecha
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引用次数: 18

Abstract

Systems biology aims to study the properties of biological systems in terms of the properties of their molecular constituents. This occurs frequently by a process of mathematical modelling. The first step in this modelling process is to unravel the interaction structure of biological systems from experimental data. Previously, an algorithm for gene network inference from gene expression perturbation data was proposed. Here, the algorithm is extended by using regression with subset selection. The performance of the algorithm is extensively evaluated on a set of data produced with gene network models at different levels of simulated experimental noise. Regression with subset selection outperforms the previously stated matrix inverse approach in the presence of experimental noise. Furthermore, this regression approach enables us to deal with under-determination, that is, when not all genes are perturbed. The results on incomplete data sets show that the new method performs well at higher number of perturbations, even when noise levels are high. At lower number of perturbations, although still being able to recover the majority of the connections, less confidence can be placed in the recovered edges.

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从嘈杂的未确定实验扰动数据中揭示基因网络。
系统生物学的目的是研究生物系统的性质,根据其分子成分的性质。这是通过数学建模过程经常发生的。建模过程的第一步是从实验数据中揭示生物系统的相互作用结构。此前,提出了一种基于基因表达扰动数据的基因网络推断算法。在此,采用带子集选择的回归对算法进行了扩展。该算法的性能在不同水平的模拟实验噪声下由基因网络模型产生的一组数据上进行了广泛的评估。在存在实验噪声的情况下,具有子集选择的回归优于先前所述的矩阵逆方法。此外,这种回归方法使我们能够处理决定不足,也就是说,不是所有的基因都受到干扰。在不完全数据集上的结果表明,即使在噪声水平很高的情况下,新方法也能在较高数量的扰动下表现良好。在较低的扰动数量下,尽管仍然能够恢复大部分连接,但可以对恢复的边缘放置较少的置信度。
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