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利用稳态数据和动力学进行网络推理

Network inference using steady-state data and Goldbeter-Koshland kinetics
课程网址: http://videolectures.net/mlsb2012_oates_inference/  
主讲教师: Chris J Oates
开课单位: 华威大学
开课时间: 2012-10-23
课程语种: 英语
中文简介:
动机:网络推理方法被广泛用于揭示分子参与者(如基因和蛋白质)之间的监管相互作用。感兴趣的网络(例如基因调控或蛋白质信号传导网络)的生物化学过程是基因拉力非线性的。在许多情况下,可获得有关相关化学动力学的知识。然而,用于连续数据的现有网络参考方法通常植根于方便的统计公式,其不利用化学动力学来指导推断。结果:这里我们提出了一种基于线性描述的稳态数据的网络推理方法。生化机制。我们使用化学动力学的平衡分析获得功能形式,然后使用稳态数据来推断网络。我们提出的方法直接适用于传统的稳态基因表达或蛋白质组学数据,不需要了解网络拓扑结构或任何动力学参数;两者都是从数据中同时学习的。我们使用从最近的机制模型和来自癌细胞系的蛋白质组学数据模拟的数据,在蛋白质磷酸化网络的背景下说明该方法。在前者中,真正的网络是已知的并且用于评估,而后者的结果与已知的生物化学进行比较。我们发现所提出的方法在估计网络拓扑方面比基于在线模型的方法更有效。\\ **可用性:**用于产生这些结果的MATLAB R2009b代码在SupplementalInformation中提供。
课程简介: **Motivation:** Network inference approaches are widely used to shed light on regulatory interplay between molecular players such as genes and proteins. Biochemical processes underlying networks of interest (e.g. gene regulatory or protein signalling networks) are gene- rally nonlinear. In many settings, knowledge is available concerning relevant chemical kinetics. However, existing network inference methods for continuous data are typically rooted in convenient statistical formulations which do not exploit chemical kinetics to guide inference.\\ **Results:** Here we present an approach to network inference for steady-state data that is rooted in nonlinear descriptions of biochemical mechanism. We use equilibrium analysis of chemical kinetics to obtain functional forms that are in turn used to infer networks using steady-state data. The approach we propose is directly applicable to conventional steady-state gene expression or proteomic data and does not require knowledge of either network topology or any kinetic parameters; both are simultaneously learned from data. We illustrate the approach in the context of protein phosphorylation networks, using data simulated from a recent mechanistic model and proteomic data from cancer cell lines. In the former, the true network is known and used for assessment, whilst in the latter results are compared against known biochemistry. We find that the proposed methodology is more effective at estimating network topology than methods based on linear models.\\ **Availability:** MATLAB R2009b code used to produce these results is provided in the Supplemental Information.
关 键 词: 稳态数据; 线性描述; 统计公式
课程来源: 视频讲座网
最后编审: 2020-06-08:cxin
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