Seim Ian, Grill Stephan W
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Systems Biology Dresden (CSBD), Dresden, Germany; Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany.
Biophys J. 2025 Mar 18;124(6):861-875. doi: 10.1016/j.bpj.2024.12.003. Epub 2024 Dec 4.
We review empirical methods that can be used to provide physical descriptions of dynamic cellular processes during development and disease. Our focus will be nonspatial descriptions and the inference of underlying interaction networks including cell-state lineages, gene regulatory networks, and molecular interactions in living cells. Our overarching questions are: How much can we learn from just observing? To what degree is it possible to infer causal and/or precise mathematical relationships from observations? We restrict ourselves to data sets arising from only observations, or experiments in which minimal perturbations have taken place to facilitate observation of the systems as they naturally occur. We discuss analysis perspectives in order from those offering the least descriptive power but requiring the least assumptions such as statistical associations. We end with those that are most descriptive, but require stricter assumptions and more previous knowledge of the systems such as causal inference and dynamical systems approaches. We hope to provide and encourage the use of a wide array of options for quantitative cell biologists to learn as much as possible from their observations at all stages of understanding of their system of interest. Finally, we provide our own recipe of how to empirically determine quantitative relationships and growth laws from live-cell microscopy data, the resultant predictions of which can then be verified with perturbation experiments. We also include an extended supplement that describes further inference algorithms and theory for the interested reader.
我们回顾了可用于对发育和疾病过程中的动态细胞过程进行物理描述的实证方法。我们的重点将是非空间描述以及对潜在相互作用网络的推断,包括细胞状态谱系、基因调控网络和活细胞中的分子相互作用。我们的首要问题是:仅通过观察我们能学到多少?从观察中推断因果关系和/或精确的数学关系的可能性有多大?我们将自己限制于仅来自观察或进行了最小扰动的实验所产生的数据集,以便于观察系统的自然状态。我们按照描述能力从低到高的顺序讨论分析视角,从那些需要最少假设(如统计关联)但描述能力最弱的视角开始。我们以那些描述性最强但需要更严格假设以及对系统有更多先验知识(如因果推断和动态系统方法)的视角结束。我们希望为定量细胞生物学家提供并鼓励他们使用各种各样的选项,以便在对感兴趣的系统的理解的各个阶段,从观察中尽可能多地学习。最后,我们提供了自己的方法,即如何从活细胞显微镜数据中凭经验确定定量关系和生长规律,其结果预测随后可通过扰动实验进行验证。我们还包括一个扩展补充内容,为感兴趣的读者描述了进一步的推断算法和理论。