Kinnunen Patrick C, Ho Kenneth K Y, Srivastava Siddhartha, Huang Chengyang, Shen Wanggang, Garikipati Krishna, Luker Gary D, Banovic Nikola, Huan Xun, Linderman Jennifer J, Luker Kathryn E
Departments of Chemical Engineering, University of Michigan, Ann Arbor, MI, United States.
Radiology, University of Michigan, Ann Arbor, MI, United States.
Front Syst Biol. 2024 Mar 8;4:1333760. doi: 10.3389/fsysb.2024.1333760. eCollection 2024.
Cellular heterogeneity is a ubiquitous aspect of biology and a major obstacle to successful cancer treatment. Several techniques have emerged to quantify heterogeneity in live cells along axes including cellular migration, morphology, growth, and signaling. Crucially, these studies reveal that cellular heterogeneity is not a result of randomness or a failure in cellular control systems, but instead is a predictable aspect of multicellular systems. We hypothesize that individual cells in complex tissues can behave as reward-maximizing agents and that differences in reward perception can explain heterogeneity. In this perspective, we introduce inverse reinforcement learning as a novel approach for analyzing cellular heterogeneity. We briefly detail experimental approaches for measuring cellular heterogeneity over time and how these experiments can generate datasets consisting of cellular states and actions. Next, we show how inverse reinforcement learning can be applied to these datasets to infer how individual cells choose different actions based on heterogeneous states. Finally, we introduce potential applications of inverse reinforcement learning to three cell biology problems. Overall, we expect inverse reinforcement learning to reveal why cells behave heterogeneously and enable identification of novel treatments based on this new understanding.
细胞异质性是生物学中普遍存在的一个方面,也是癌症治疗成功的主要障碍。已经出现了几种技术来量化活细胞在细胞迁移、形态、生长和信号传导等轴线上的异质性。至关重要的是,这些研究表明,细胞异质性不是随机性的结果,也不是细胞控制系统失灵的结果,而是多细胞系统可预测的一个方面。我们假设复杂组织中的单个细胞可以表现为奖励最大化的主体,并且奖励感知的差异可以解释异质性。从这个角度来看,我们引入逆强化学习作为一种分析细胞异质性的新方法。我们简要详细介绍了随时间测量细胞异质性的实验方法,以及这些实验如何生成由细胞状态和行为组成的数据集。接下来,我们展示了逆强化学习如何应用于这些数据集,以推断单个细胞如何根据异质状态选择不同的行为。最后,我们介绍了逆强化学习在三个细胞生物学问题上的潜在应用。总体而言,我们期望逆强化学习能够揭示细胞行为异质化的原因,并基于这一新认识实现新型治疗方法的识别。