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有限状态线性模型下基因调控网络的重建

Reconstruction of gene regulatory networks under the finite state linear model.

作者信息

Ruklisa Dace, Brazma Alvis, Viksna Juris

机构信息

Institute of Mathematics and Computer Science, University of Latvia, Rainis boulevard 29, Riga LV-1459, Latvia.

出版信息

Genome Inform. 2005;16(2):225-36.

Abstract

We study the Finite State Linear Model (FSLM) for modelling gene regulatory networks proposed by A. Brazma and T. Schlitt in [4]. The model incorporates biologically intuitive gene regulatory mechanism similar to that in Boolean networks, and can describe also the continuous changes in protein levels. We consider several theoretical properties of this model; in particular we show that the problem whether a particular gene will reach an active state is algorithmically unsolvable. This imposes some practical difficulties in simulation and reverse engineering of FSLM networks. Nevertheless, our simulation experiments show that sufficiently many of FSLM networks exhibit a regular behaviour and that the model is still quite adequate to describe biological reality. We also propose a comparatively efficient O(2(K)n(K+1)M(2K)m log m) time algorithm for reconstruction of FSLM networks from experimental data. Experiments on reconstruction of random networks are performed to estimate the running time of the algorithm in practice, as well as the number of measurements needed for successful network reconstruction.

摘要

我们研究了A. Brazma和T. Schlitt在[4]中提出的用于建模基因调控网络的有限状态线性模型(FSLM)。该模型纳入了与布尔网络中类似的具有生物学直观性的基因调控机制,并且还能够描述蛋白质水平的连续变化。我们考虑了此模型的几个理论特性;特别地,我们证明了特定基因是否会达到激活状态这一问题在算法上是不可解的。这给FSLM网络的模拟和逆向工程带来了一些实际困难。然而,我们的模拟实验表明,足够多的FSLM网络呈现出规则行为,并且该模型对于描述生物现实仍然相当适用。我们还提出了一种相对高效的O(2(K)n(K + 1)M(2K)m log m)时间算法,用于从实验数据重建FSLM网络。进行了随机网络重建实验,以估计该算法在实际中的运行时间,以及成功进行网络重建所需的测量次数。

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