Domijan Mirela, Brown Paul E, Shulgin Boris V, Rand David A
Current address: The Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge, CB2 1LR, UK.
Warwick Systems Biology Centre, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
BMC Bioinformatics. 2016 Mar 10;17:124. doi: 10.1186/s12859-016-0972-2.
Over the last decade sensitivity analysis techniques have been shown to be very useful to analyse complex and high dimensional Systems Biology models. However, many of the currently available toolboxes have either used parameter sampling, been focused on a restricted set of model observables of interest, studied optimisation of a objective function, or have not dealt with multiple simultaneous model parameter changes where the changes can be permanent or temporary.
Here we introduce our new, freely downloadable toolbox, PeTTSy (Perturbation Theory Toolbox for Systems). PeTTSy is a package for MATLAB which implements a wide array of techniques for the perturbation theory and sensitivity analysis of large and complex ordinary differential equation (ODE) based models. PeTTSy is a comprehensive modelling framework that introduces a number of new approaches and that fully addresses analysis of oscillatory systems. It examines sensitivity analysis of the models to perturbations of parameters, where the perturbation timing, strength, length and overall shape can be controlled by the user. This can be done in a system-global setting, namely, the user can determine how many parameters to perturb, by how much and for how long. PeTTSy also offers the user the ability to explore the effect of the parameter perturbations on many different types of outputs: period, phase (timing of peak) and model solutions. PeTTSy can be employed on a wide range of mathematical models including free-running and forced oscillators and signalling systems. To enable experimental optimisation using the Fisher Information Matrix it efficiently allows one to combine multiple variants of a model (i.e. a model with multiple experimental conditions) in order to determine the value of new experiments. It is especially useful in the analysis of large and complex models involving many variables and parameters.
PeTTSy is a comprehensive tool for analysing large and complex models of regulatory and signalling systems. It allows for simulation and analysis of models under a variety of environmental conditions and for experimental optimisation of complex combined experiments. With its unique set of tools it makes a valuable addition to the current library of sensitivity analysis toolboxes. We believe that this software will be of great use to the wider biological, systems biology and modelling communities.
在过去十年中，灵敏度分析技术已被证明对于分析复杂的高维系统生物学模型非常有用。然而，许多当前可用的工具箱要么使用参数采样，要么专注于一组有限的感兴趣的模型可观测量，研究目标函数的优化，或者没有处理多个同时发生的模型参数变化，其中这些变化可以是永久性的或临时性的。
在此，我们介绍我们新的、可免费下载的工具箱PeTTSy（系统扰动理论工具箱）。PeTTSy是一个用于MATLAB的软件包，它实现了一系列用于基于大型复杂常微分方程（ODE）模型的扰动理论和灵敏度分析的技术。PeTTSy是一个全面的建模框架，引入了许多新方法，并全面解决了振荡系统的分析问题。它研究模型对参数扰动的灵敏度分析，其中扰动的时间、强度、长度和整体形状可由用户控制。这可以在系统全局设置中完成，即用户可以确定扰动多少个参数、扰动幅度以及扰动持续时间。PeTTSy还为用户提供了探索参数扰动对许多不同类型输出的影响的能力：周期、相位（峰值时间）和模型解。PeTTSy可应用于广泛的数学模型，包括自由运行和受迫振荡器以及信号系统。为了使用费希尔信息矩阵进行实验优化，它有效地允许将模型的多个变体（即具有多个实验条件的模型）组合起来，以确定新实验的值。它在分析涉及许多变量和参数的大型复杂模型时特别有用。
PeTTSy是用于分析调节和信号系统大型复杂模型的综合工具。它允许在各种环境条件下对模型进行模拟和分析，并对复杂的组合实验进行实验优化。凭借其独特的工具集，它为当前的灵敏度分析工具箱库增添了有价值的内容。我们相信该软件将对更广泛的生物学、系统生物学和建模社区非常有用。
