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Combining tree-based and dynamical systems for the inference of gene regulatory networks

机译:结合基于树和动力学的系统来推断基因调控网络

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摘要

>Motivation: Reconstructing the topology of gene regulatory networks (GRNs) from time series of gene expression data remains an important open problem in computational systems biology. Existing GRN inference algorithms face one of two limitations: model-free methods are scalable but suffer from a lack of interpretability and cannot in general be used for out of sample predictions. On the other hand, model-based methods focus on identifying a dynamical model of the system. These are clearly interpretable and can be used for predictions; however, they rely on strong assumptions and are typically very demanding computationally.>Results: Here, we propose a new hybrid approach for GRN inference, called Jump3, exploiting time series of expression data. Jump3 is based on a formal on/off model of gene expression but uses a non-parametric procedure based on decision trees (called ‘jump trees’) to reconstruct the GRN topology, allowing the inference of networks of hundreds of genes. We show the good performance of Jump3 on in silico and synthetic networks and applied the approach to identify regulatory interactions activated in the presence of interferon gamma.>Availability and implementation: Our MATLAB implementation of Jump3 is available at .>Contact: or >Supplementary information: are available at Bioinformatics online.
机译:>动机:从基因表达数据的时间序列重建基因调控网络(GRN)的拓扑结构仍然是计算系统生物学中一个重要的开放问题。现有的GRN推理算法面临两个局限性之一:无模型方法具有可扩展性,但缺乏可解释性,通常不能用于样本外预测。另一方面,基于模型的方法着重于识别系统的动力学模型。这些是很容易解释的,可以用于预测。 >结果:在这里,我们提出了一种新的GRN推理混合方法,称为Jump3,它利用了表达数据的时间序列。 Jump3基于正式的基因表达开/关模型,但使用基于决策树(称为“跳跃树”)的非参数过程来重建GRN拓扑,从而可以推断数百个基因的网络。我们在计算机和合成网络上显示了Jump3的良好性能,并应用了该方法来识别存在干扰素γ时激活的调节相互作用。>可用性和实现:我们的MATLAB Jump3实现可从。< strong>联系方式:或>补充信息:可从生物信息学在线获得。

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