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Modelling Nonstationary Gene Regulatory Processes

机译:建模非平稳基因调控过程

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摘要

An important objective in systems biology is to infer gene regulatory networks from postgenomic data, and dynamic Bayesian networks have been widely applied as a popular tool to this end. The standard approach for nondiscretised data is restricted to a linear model and a homogeneous Markov chain. Recently, various generalisations based on changepoint processes and free allocation mixture models have been proposed. The former aim to relax the homogeneity assumption, whereas the latter are more flexible and, in principle, more adequate for modelling nonlinear processes. In our paper, we compare both paradigms and discuss theoretical shortcomings of the latter approach. We show that a model based on the changepoint process yields systematically better results than the free allocation model when inferring nonstationary gene regulatory processes from simulated gene expression time series. We further cross-compare the performance of both models on three biological systems: macrophages challenged with viral infection, circadian regulation in Arabidopsis thaliana, and morphogenesis in Drosophila melanogaster.
机译:系统生物学的一个重要目标是从后基因组数据推断基因调控网络,为此,动态贝叶斯网络已被广泛用作一种流行的工具。非离散数据的标准方法仅限于线性模型和齐次马尔可夫链。近来,已经提出了基于变更点过程和自由分配混合模型的各种概括。前者旨在放松同质性假设,而后者则更为灵活,并且原则上更适合于建模非线性过程。在我们的论文中,我们比较了这两种范式,并讨论了后一种方法的理论缺陷。我们表明,从模拟基因表达时间序列推断非平稳基因调控过程时,基于变更点过程的模型比自由分配模型可系统地产生更好的结果。我们进一步交叉比较两个模型在三种生物系统上的性能:受到病毒感染的巨噬细胞,拟南芥中的昼夜节律调节以及果蝇中的形态发生。

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