Department of Mathematics, University of British Columbia, Vancouver, Canada.
PLoS Comput Biol. 2021 Dec 3;17(12):e1009466. doi: 10.1371/journal.pcbi.1009466. eCollection 2021 Dec.
Understanding how cells change their identity and behaviour in living systems is an important question in many fields of biology. The problem of inferring cell trajectories from single-cell measurements has been a major topic in the single-cell analysis community, with different methods developed for equilibrium and non-equilibrium systems (e.g. haematopoeisis vs. embryonic development). We show that optimal transport analysis, a technique originally designed for analysing time-courses, may also be applied to infer cellular trajectories from a single snapshot of a population in equilibrium. Therefore, optimal transport provides a unified approach to inferring trajectories that is applicable to both stationary and non-stationary systems. Our method, StationaryOT, is mathematically motivated in a natural way from the hypothesis of a Waddington's epigenetic landscape. We implement StationaryOT as a software package and demonstrate its efficacy in applications to simulated data as well as single-cell data from Arabidopsis thaliana root development.
理解细胞如何在生命系统中改变其身份和行为是许多生物学领域的一个重要问题。从单细胞测量中推断细胞轨迹一直是单细胞分析领域的一个主要课题,针对平衡和非平衡系统(例如造血与胚胎发育)已经开发出不同的方法。我们表明,最优传输分析,一种最初设计用于分析时程的技术,也可以应用于从平衡群体的单个快照中推断细胞轨迹。因此,最优传输为推断轨迹提供了一种统一的方法,适用于静止和非静止系统。我们的方法,StationaryOT,是从 Waddington 的表观遗传景观假说自然地从数学上激发的。我们将 StationaryOT 实现为一个软件包,并证明它在模拟数据以及拟南芥根发育的单细胞数据中的应用中的有效性。