Construction of a 3D whole organism spatial atlas by joint modelling of multiple slices with deep neural networks

Spatial transcriptomics (ST) technologies are revolutionizing the way to explore the spatial architecture of tissues. Currently, ST data analysis is often restricted to a single two-dimensional (2D) tissue slice, limiting our capacity to understand biological processes that take place in 3D space. Here we present STitch3D, a unified framework that integrates multiple ST slices to reconstruct 3D cellular structures. By jointly modelling multiple slices and integrating them with single-cell RNA-sequencing data, STitch3D simultaneously identifies 3D spatial regions with coherent gene-expression levels and reveals 3D cell-type distributions. STitch3D distinguishes biological variation among slices from batch effects, and effectively borrows information across slices to assemble powerful 3D models. Through comprehensive experiments, we demonstrate STitch3D’s performance in building comprehensive 3D architectures, which allow 3D analysis in the entire tissue region or even the whole organism. The outputs of STitch3D can be used for multiple downstream tasks, enabling a comprehensive understanding of biological systems. Computational methods for analysing single 2D tissue slices from spatial transcriptomics studies are well established, but their extension to the 3D domain is challenging. Wang et al. develop a deep learning framework that can perform 3D reconstruction of cellular structures in tissues as well as whole organisms.