The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.
PLoS Comput Biol. 2019 Mar 28;15(3):e1006577. doi: 10.1371/journal.pcbi.1006577. eCollection 2019 Mar.
The complexity of morphogenesis poses a fundamental challenge to understanding the mechanisms governing the formation of biological patterns and structures. Over the past century, numerous processes have been identified as critically contributing to morphogenetic events, but the interplay between the various components and aspects of pattern formation have been much harder to grasp. The combination of traditional biology with mathematical and computational methods has had a profound effect on our current understanding of morphogenesis and led to significant insights and advancements in the field. In particular, the theoretical concepts of reaction-diffusion systems and positional information, proposed by Alan Turing and Lewis Wolpert, respectively, dramatically influenced our general view of morphogenesis, although typically in isolation from one another. In recent years, agent-based modeling has been emerging as a consolidation and implementation of the two theories within a single framework. Agent-based models (ABMs) are unique in their ability to integrate combinations of heterogeneous processes and investigate their respective dynamics, especially in the context of spatial phenomena. In this review, we highlight the benefits and technical challenges associated with ABMs as tools for examining morphogenetic events. These models display unparalleled flexibility for studying various morphogenetic phenomena at multiple levels and have the important advantage of informing future experimental work, including the targeted engineering of tissues and organs.
形态发生的复杂性对理解控制生物模式和结构形成的机制构成了根本性的挑战。在过去的一个世纪中,已经确定了许多过程对形态发生事件有重要贡献,但模式形成的各种组成部分和方面之间的相互作用却更难理解。传统生物学与数学和计算方法的结合对我们当前对形态发生的理解产生了深远的影响,并在该领域取得了重大的见解和进展。特别是,艾伦·图灵(Alan Turing)和刘易斯·沃尔珀特(Lewis Wolpert)分别提出的反应扩散系统和位置信息的理论概念,极大地影响了我们对形态发生的总体看法,尽管它们通常彼此孤立。近年来,基于主体的建模作为这两个理论在单个框架内的整合和实现而崭露头角。基于主体的模型(ABM)具有独特的能力,可以整合异构过程的组合并研究它们各自的动态,特别是在空间现象的背景下。在这篇综述中,我们强调了 ABM 作为研究形态发生事件的工具所具有的优势和技术挑战。这些模型在研究多个层次的各种形态发生现象方面具有无与伦比的灵活性,并且具有一个重要的优势,即可以为未来的实验工作提供信息,包括组织和器官的靶向工程。