Modeling single cell trajectory using forward-backward stochastic differential equations

PLoS Comput Biol. 2024 Apr 15;20(4):e1012015. doi: 10.1371/journal.pcbi.1012015. eCollection 2024 Apr.

Abstract

Recent advances in single-cell sequencing technology have provided opportunities for mathematical modeling of dynamic developmental processes at the single-cell level, such as inferring developmental trajectories. Optimal transport has emerged as a promising theoretical framework for this task by computing pairings between cells from different time points. However, optimal transport methods have limitations in capturing nonlinear trajectories, as they are static and can only infer linear paths between endpoints. In contrast, stochastic differential equations (SDEs) offer a dynamic and flexible approach that can model non-linear trajectories, including the shape of the path. Nevertheless, existing SDE methods often rely on numerical approximations that can lead to inaccurate inferences, deviating from true trajectories. To address this challenge, we propose a novel approach combining forward-backward stochastic differential equations (FBSDE) with a refined approximation procedure. Our FBSDE model integrates the forward and backward movements of two SDEs in time, aiming to capture the underlying dynamics of single-cell developmental trajectories. Through comprehensive benchmarking on multiple scRNA-seq datasets, we demonstrate the superior performance of FBSDE compared to other methods, highlighting its efficacy in accurately inferring developmental trajectories.

MeSH terms

  • Models, Theoretical*
  • Stochastic Processes

Grants and funding

DK and ZZ acknowledge financial support from a Catalyst Grant from Data Science Institute and Medicine by Design, University of Toronto. KZ and JZ are partially supported by CANSSI (Canadian Statistical Sciences Institute). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.