Mapping cells through time and space with moscot

Area of Science:

• Computational biology
• Genomics
• Developmental biology

Background:

• Single-cell genomic technologies offer multimodal profiling but face limitations in capturing native temporal dynamics and spatial context.
• Optimal transport methods can recover cellular context but often struggle with multimodality and scalability for large single-cell atlases.

Purpose of the Study:

• Introduce moscot (multi-omics single-cell optimal transport), a scalable computational framework designed for single-cell genomics.
• Enable the integration of multimodal data and overcome limitations in reconstructing cellular context across space and time.
• Facilitate the analysis of complex biological systems, including developmental trajectories and cell lineage relationships.

Main Methods:

• Developed moscot, a scalable framework for optimal transport supporting multimodality in single-cell genomics.
• Applied moscot to reconstruct developmental trajectories of 1.7 million cells across 20 time points in mouse embryos.
• Utilized moscot.spatiotemporal to analyze gene expression across spatial and temporal dimensions for mouse embryogenesis.
• Integrated gene expression and chromatin accessibility data to resolve cell lineage relationships in pancreas development.

Main Results:

• Successfully reconstructed developmental trajectories for a large-scale mouse embryo dataset.
• Enriched spatial transcriptomic data and aligned multiple brain sections using multimodal information.
• Uncovered spatiotemporal dynamics of mouse embryogenesis using gene expression data.
• Resolved endocrine-lineage relationships in pancreas development and validated NEUROD2's role in epsilon progenitor cells.

Conclusions:

• Moscot provides a scalable and versatile framework for multimodal single-cell optimal transport.
• The framework enables comprehensive reconstruction of cellular context, developmental trajectories, and spatiotemporal dynamics.
• Moscot facilitates novel discoveries in developmental biology and cell lineage analysis, supported by experimental validation.