Harnessing agent-based frameworks in CellAgentChat to unravel cell–cell interactions from single-cell and spatial transcriptomics

Abstract

Understanding cell–cell interactions (CCIs) is essential yet challenging owing to the inherent intricacy and diversity of cellular dynamics. Existing approaches often analyze global patterns of CCIs using statistical frameworks, missing the nuances of individual cell behavior owing to their focus on aggregate data. This makes them insensitive in complex environments where the detailed dynamics of cell interactions matter. We introduce CellAgentChat, an agent-based model (ABM) designed to decipher CCIs from single-cell RNA sequencing and spatial transcriptomics data. This approach models biological systems as collections of autonomous agents governed by biologically inspired principles and rules. Validated across eight diverse single-cell data sets, CellAgentChat demonstrates its effectiveness in detecting intricate signaling events across different cell populations. Moreover, CellAgentChat offers the ability to generate animated visualizations of single-cell interactions and provides flexibility in modifying agent behavior rules, facilitating thorough exploration of both close and distant cellular communications. Furthermore, CellAgentChat leverages ABM features to enable intuitive in silico perturbations via agent rule modifications, facilitating the development of novel intervention strategies. This ABM method unlocks an in-depth understanding of cellular signaling interactions across various biological contexts, thereby enhancing in silico studies for cellular communication–based therapies.