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arXiv 1504.06273q-bio.MN
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从生物网络的布尔模型预测遗传相互作用

Predicting genetic interactions from Boolean models of biological networks

Laurence Calzone, Emmanuel Barillot, Andrei Zinovyev

摘要:

遗传相互作用可以定义为双基因突变的表型定量效应与使用简单(例如,乘法或线性加法)统计模型。实验表征的模式生物的遗传相互作用网络提供了重要的见解不同的生物功能之间的关系。我们描述了一种计算方法,允许系统地和定量地表征一个布尔数学模型的生物网络中的遗传相互作用的所有损失的功能和增益的功能突变相对于所有模型的表型或输出。我们使用MaBoSS软件中定义的概率框架,基于连续时间马尔可夫链和随机模拟。此外,我们提出了几种计算工具,用于研究双突变体在模型表型概率空间中的分布。我们证明了这种方法在三个已发表的模型,我们得出的遗传相互作用网络,并分析其属性。我们分类所获得的相互作用,根据其类上位性,依赖于所选择的初始条件和表型。使用这种方法验证数学模型从实验数据和设计新的实验进行了讨论。

英文摘要:

Genetic interaction can be defined as a deviation of the phenotypic quantitative effect of a double gene mutation from the effect predicted from single mutations using a simple (e.g., multiplicative or linear additive) statistical model. Experimentally characterized genetic interaction networks in model organisms provide important insights into relationships between different biological functions. We describe a computational methodology allowing to systematically and quantitatively characterize a Boolean mathematical model of a biological network in terms of genetic interactions between all loss of function and gain of function mutations with respect to all model phenotypes or outputs. We use the probabilistic framework defined in MaBoSS software, based on continuous time Markov chains and stochastic simulations. In addition, we suggest several computational tools for studying the distribution of double mutants in the space of model phenotype probabilities. We demonstrate this methodology on three published models for each of which we derive the genetic interaction networks and analyze their properties. We classify the obtained interactions according to their class of epistasis, dependence on the chosen initial conditions and phenotype. The use of this methodology for validating mathematical models from experimental data and designing new experiments is discussed.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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