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Integrating literature-constrained and data-driven inference of signalling networks

机译:集成文献约束和数据驱动的信令网络推理

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摘要

>Motivation: Recent developments in experimental methods facilitate increasingly larger signal transduction datasets. Two main approaches can be taken to derive a mathematical model from these data: training a network (obtained, e.g., from literature) to the data, or inferring the network from the data alone. Purely data-driven methods scale up poorly and have limited interpretability, whereas literature-constrained methods cannot deal with incomplete networks.>Results: We present an efficient approach, implemented in the R package CNORfeeder, to integrate literature-constrained and data-driven methods to infer signalling networks from perturbation experiments. Our method extends a given network with links derived from the data via various inference methods, and uses information on physical interactions of proteins to guide and validate the integration of links. We apply CNORfeeder to a network of growth and inflammatory signalling. We obtain a model with superior data fit in the human liver cancer HepG2 and propose potential missing pathways.>Availability: CNORfeeder is in the process of being submitted to Bioconductor and in the meantime available at .>Contact: >Supplementary information: are available at Bioinformatics online.
机译:>动机:实验方法的最新发展促进了越来越大的信号转导数据集。可以采用两种主要方法从这些数据中得出数学模型:对数据训练网络(例如从文献中获得),或者仅从数据中推断网络。纯粹由数据驱动的方法扩展性差且可解释性有限,而受文献限制的方法无法处理不完整的网络。>结果:我们提出了一种有效的方法,该方法在R包CNORfeeder中实现,可以整合文献-约束和数据驱动的方法从扰动实验中推断出信号网络。我们的方法利用通过各种推断方法从数据得出的链接扩展了给定的网络,并使用有关蛋白质物理相互作用的信息来指导和验证链接的整合。我们将CNORfeeder应用于生长和炎症信号传递网络。我们获得了具有与人类肝癌HepG2匹配的优异数据的模型,并提出了可能的缺失途径。>可用性: CNORfeeder正在提交给Bioconductor,同时可通过以下网址获取。>联系方式: >补充信息:可从在线生物信息学获得。

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