Jashnsaz Hossein, Fox Zachary R, Munsky Brian, Neuert Gregor
Department of Molecular Physiology and Biophysics, School of Medicine, Vanderbilt University, Nashville, TN 37232 USA.
Inria Paris, Paris 75012, France.
STAR Protoc. 2021 Jul 7;2(3):100660. doi: 10.1016/j.xpro.2021.100660. eCollection 2021 Sep 17.
This protocol provides a step-by-step approach to perturb single cells with time-varying stimulation profiles, collect distinct signaling responses, and use these to infer a system of ordinary differential equations to capture and predict dynamics of protein-protein regulation in signal transduction pathways. The models are validated by predicting the signaling activation upon new cell stimulation conditions. In comparison to using standard step-like stimulations, application of diverse time-varying cell stimulations results in better inference of model parameters and substantially improves model predictions. For complete details on the use and results of this protocol, please refer to Jashnsaz et al. (2020).
本方案提供了一种逐步的方法，用于对单细胞施加随时间变化的刺激模式，收集不同的信号响应，并利用这些响应来推断常微分方程组，以捕捉和预测信号转导途径中蛋白质-蛋白质调控的动态变化。通过预测新的细胞刺激条件下的信号激活来验证模型。与使用标准的阶梯状刺激相比，应用多种随时间变化的细胞刺激能够更好地推断模型参数，并显著提高模型预测能力。有关本方案的使用和结果的完整详细信息，请参阅贾什恩萨兹等人（2020年）的文献。
