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使用调节动力学的ODE模型验证推断的基因网络

Validating inferred gene networks using ODE models of regulation dynamics
课程网址: http://videolectures.net/licsb08_erguler_vig/  
主讲教师: Michael Stumpf
开课单位: 帝国理工学院
开课时间: 2008-04-17
课程语种: 英语
中文简介:
从表达数据推断基因调控网络仍然是生物信息学和系统生物学中最重要和最具挑战性的问题之一。传统上,通过与实验确定的网络进行比较来执行推​​断网络的验证:如果推断的网络(或更一般地,其子网之一)准确地描述了已知的生物行为,那么我们将对其有效性具有更大程度的信任。然而,推断的网络通常预测许多以前未被观察到的新的交互。通过实验验证每个预测将是一项困难,耗时,昂贵且最终繁琐的任务。我们在这里提出了一种数据驱动的方法,用于验证推断的基因调控网络。在我们工作的第一阶段,我们从时间过程mRNA表达数据推断出一个调节网络。假设推断网络是正确的,我们提出参数ODE模型将观察到的mRNA表达水平与隐藏的转录因子活性联系起来。在第二阶段,我们推断ODE系统的参数,然后评估结果模型描述观察到的表达数据的动态行为的程度。对数据的良好描述将支持推断网络和ODE模型的有效性,而不合适将表明在某种程度上重新模拟模型。通过将其应用于酵母基因表达数据来说明该方法的价值。
课程简介: Inferring gene regulatory networks from expression data remains one of the most important and challenging problems in bioinformatics and systems biology. Traditionally, validation of inferred networks is performed by comparison with experimentally identifiedtrue networks: if the inferred network (or, more generally, one of its subnets) accurately describes known biological behaviour, then we will have a greater degree of belief in its validity. However, inferred networks typically predict many new interactions that have not previously been observed. Verifying each of these predictions experimentally would be a difficult, time-consuming, expensive, and ultimately tedious, task. We here present a data-driven method for validating inferred gene regulatory networks. In the first stage of our work, we infer a regulatory network from time-course mRNA expression data. Assuming the inferred network to be correct, we propose a parametric ODE model to link the observed mRNA expression levels with the hidden transcription factor activity. In the second stage, we infer the parameters of our ODE system and then assess how well the resulting model describes the dynamic behaviour of the observed expression data. A good description of the data would lend support to the validity of both the inferred network and the ODE model, while a poor fit would suggest a reformulation of the model at some level. The value of this approach is illustrated by applying it to yeast gene expression data.
关 键 词: 基因调控网络; 转录因子; 酵母基因; ODE系统
课程来源: 视频讲座网
最后编审: 2020-01-16:chenxin
阅读次数: 71