Systems Biology Centre, University of Warwick, Coventry, CV4 7AL, UK.
Interface Focus. 2011 Dec 6;1(6):857-70. doi: 10.1098/rsfs.2011.0053. Epub 2011 Aug 10.
Inferring the topology of a gene-regulatory network (GRN) from genome-scale time-series measurements of transcriptional change has proved useful for disentangling complex biological processes. To address the challenges associated with this inference, a number of competing approaches have previously been used, including examples from information theory, Bayesian and dynamic Bayesian networks (DBNs), and ordinary differential equation (ODE) or stochastic differential equation. The performance of these competing approaches have previously been assessed using a variety of in silico and in vivo datasets. Here, we revisit this work by assessing the performance of more recent network inference algorithms, including a novel non-parametric learning approach based upon nonlinear dynamical systems. For larger GRNs, containing hundreds of genes, these non-parametric approaches more accurately infer network structures than do traditional approaches, but at significant computational cost. For smaller systems, DBNs are competitive with the non-parametric approaches with respect to computational time and accuracy, and both of these approaches appear to be more accurate than Granger causality-based methods and those using simple ODEs models.
从全基因组规模的转录变化时间序列测量中推断基因调控网络 (GRN) 的拓扑结构已被证明对于分解复杂的生物过程非常有用。为了解决与这种推断相关的挑战,之前已经使用了许多竞争方法,包括信息论、贝叶斯和动态贝叶斯网络 (DBN) 以及常微分方程 (ODE) 或随机微分方程的例子。这些竞争方法的性能之前已经使用各种计算机模拟和体内数据集进行了评估。在这里,我们通过评估包括基于非线性动力系统的新的非参数学习方法在内的更新的网络推断算法的性能来重新审视这项工作。对于包含数百个基因的更大的 GRN,这些非参数方法比传统方法更准确地推断网络结构,但计算成本很高。对于较小的系统,DBN 在计算时间和准确性方面与非参数方法具有竞争力,并且这两种方法似乎比基于格兰杰因果关系的方法和使用简单 ODE 模型的方法更准确。