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使用图形模型反向工程基因和蛋白质调控网络:一项比较评估研究

Reverse engineering gene and protein regulatory networks using graphical models: A comparative evaluation study
课程网址: http://videolectures.net/pmnp07_grzegorczyk_regp/  
主讲教师: Marco Grzegorczyk
开课单位: BioSS-苏格兰生物数学与统计
开课时间: 2007-09-05
课程语种: 英语
中文简介:
系统生物学的主要目标之一是从后基因组数据中推断生物化学途径和调控网络的结构,如微阵列基因表达和细胞仪蛋白表达数据。文献中提出了各种逆向工程机器学习方法,了解它们的相对优缺点很重要。在演讲中,三种不同的图形模型机器学习方法,即关联网络、高斯图形模型和贝叶斯网络,在真实的细胞蛋白数据和来自RAF信号通路的模拟数据上进行了交叉比较。关联网络基于成对的关联分数,并且易于实现。但这种推断并不是在整个系统的背景下进行的,也不可能区分直接联想和间接联想。高斯图形模型解决了这两个缺点,其中两个变量之间的部分相关性,以所有其他领域变量为条件,被用作关联得分。贝叶斯网络是用于条件依赖和独立关系的更灵活的概率图形模型。贝叶斯网络基于有向无环图,可用于分析干预数据,以确定假定的因果关系。经验结果是通过应用Schaefer和Strimmer(2005)的收缩估计器来计算高斯图形模型的逆协方差矩阵而获得的,并且贝叶斯网络推理是通过使用阶马尔可夫链蒙特卡罗(MCMC)从后验分布中采样贝叶斯网络来完成的,如Friedman和Koller(2003)所提出的。实验结果是通过分析Sachs等人(2005)中报道的RAF蛋白信号网络的数据获得的;其描述了人类免疫系统细胞中11种磷酸化蛋白和磷脂的相互作用。因此,区分了Sachs等人(2005)中报道的真实细胞术蛋白活性测量和合成数据以及纯观察和介入数据。通过在没有任何干扰的情况下被动监测系统来获得观测数据,而通过主动操纵变量来获得干预数据,例如使用基因敲除实验。这项实证研究的详细结果已发表在Werhli等人(2006年)和Grzegorczyk(2007年)上。这三个主要发现可以总结如下。首先,仅在高斯观测数据上,发现贝叶斯网络和高斯图形模型的性能优于相关性网络。其次,对于观测数据,贝叶斯网络和高斯图形模型之间没有观察到显著差异。第三,只有在介入数据方面,贝叶斯网络的表现明显优于其他两种方法。
课程简介: One of the major goals in systems biology is to infer the architecture of biochemical pathways and regulatory networks from postgenomic data, such as microarray gene expression and cytometric protein expression data. Various reverse engineering Machine Learning methods have been proposed in the literature, and it is important to understand their relative merits and shortcomings. In the talk the learning performances of three different graphical models machine learning methods, namely Relevance networks, Gaussian Graphical Models, and Bayesian networks, are cross-compared on real cytometric protein data and simulated data from the RAF signalling pathway. Relevance networks are based on pairwise association scores and straightforward to implement. But the inference is not done in the context of the whole system and there is no possibility to distinguished between direct and indirect associations. Both shortcomings are addressed by Gaussian graphical models, where the partial correlation between two variables, conditional on all the other domain variables, is employed as association score. Bayesian networks are more flexible probabilistic graphical models for conditional dependence and independence relations. Bayesian networks are based on directed acyclic graphs and can be exploited to analyse interventional data for identifying putative causal interactions. The empirical results were obtained by applying the shrinkage estimator of Schaefer and Strimmer (2005) to compute the inverse covariance matrix for Gaussian Graphical Models, and Bayesian network inference was done by sampling BNs from the posterior distribution with order Markov chain Monte Carlo (MCMC), as proposed by Friedman and Koller (2003). The experimental results were obtained by analysing data from the RAF protein signalling network reported in Sachs et al. (2005); which describes the interaction of eleven phosphorylated proteins and phospholipids in human immune system cells. Thereby it was distinguished between real cytometric protein activity measurements reported in Sachs et al. (2005) and synthetically generated data as well as between pure observational and interventional data. Observational data are obtained by passively monitoring the system without any interference while interventional data are obtained by actively manipulating variables, e.g. using gene knock-out experiments. Detailed results of this empirical study have been published in Werhli et al. (2006) and Grzegorczyk (2007). The three main findings can be summarized as follows. First, exclusively on Gaussian observational data, Bayesian networks and Gaussian graphical models were found to outperform Relevance networks. Second, for observational data no significant difference between Bayesian networks and Gaussian Graphical models was observed. Third, only for interventional data Bayesian networks clearly performed superior to the other two approaches.
关 键 词: 系统生物学; 工程机器; 贝叶斯网络
课程来源: 视频讲座网
数据采集: 2023-04-20:chenjy
最后编审: 2023-05-13:chenjy
阅读次数: 18