GAMES: A Dynamic Model Development Workflow for Rigorous Characterization of Synthetic Genetic Systems.

GAMES: A Dynamic Model Development Workflow for Rigorous Characterization of Synthetic Genetic Systems.
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DOI:
10.1021/acssynbio.1c00528
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发表时间:
2022-02-18
影响因子:
4.7
通讯作者:
Leonard, Joshua N.
Leonard, Joshua N.
中科院分区:
生物学2区
文献类型:
--
作者:
Dray, Kate E.;Muldoon, Joseph J.;Mangan, Niall M.;Bagheri, Neda;Leonard, Joshua N.

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数学建模对于推进对合成生物系统的理解和设计是无价的。然而,模型开发过程复杂且往往不直观,需要对各种计算任务进行迭代,并与实验数据进行比较。特设模型开发可能对开发过程本身的再现和批判性分析构成障碍,减少潜在的影响并抑制进一步的模型开发和协作。为了帮助从业者应对这些挑战,我们介绍了游戏:用于生成和分析用于探索合成系统的模型的工作流程,包括自动化和人在循环过程。我们系统地考虑了开发动态模型的过程,包括模型制定、参数估计、参数可辨识性、实验设计、模型简化、模型改进和模型选择。我们用一个化学反应性转录因子的案例研究来演示这个工作流程。本教程中提供的通用工作流可以使生物学家更容易地为各种应用程序构建和分析模型。
Mathematical modeling is invaluable for advancing understanding and design of synthetic biological systems. However, the model development process is complicated and often unintuitive, requiring iteration on various computational tasks and comparisons with experimental data. Ad hoc model development can pose a barrier to reproduction and critical analysis of the development process itself, reducing potential impact and inhibiting further model development and collaboration. To help practitioners manage these challenges, we introduce GAMES: a workflow for Generation and Analysis of Models for Exploring Synthetic systems that includes both automated and human-in-the-loop processes. We systematically consider the process of developing dynamic models, including model formulation, parameter estimation, parameter identifiability, experimental design, model reduction, model refinement, and model selection. We demonstrate the workflow with a case study on a chemically responsive transcription factor. The generalizable workflow presented in this tutorial can enable biologists to more readily build and analyze models for various applications.
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