AI-driven 3D Spatial Transcriptomics

TL;DR

VORTEX is an AI framework that predicts 3D spatial transcriptomics from minimal 2D data, enabling scalable, high-throughput, and non-destructive volumetric tissue analysis for biomedical research.

Contribution

The paper introduces VORTEX, a novel AI method that combines 3D tissue morphology with minimal 2D data to generate comprehensive 3D gene expression maps, overcoming limitations of existing techniques.

Findings

Enables dense 3D transcriptomics with minimal tissue sectioning

Scales to large tissue volumes efficiently

Provides cost-effective, non-destructive volumetric insights

Abstract

A comprehensive three-dimensional (3D) map of tissue architecture and gene expression is crucial for illuminating the complexity and heterogeneity of tissues across diverse biomedical applications. However, most spatial transcriptomics (ST) approaches remain limited to two-dimensional (2D) sections of tissue. Although current 3D ST methods hold promise, they typically require extensive tissue sectioning, are complex, are not compatible with non-destructive 3D tissue imaging technologies, and often lack scalability. Here, we present VOlumetrically Resolved Transcriptomics EXpression (VORTEX), an AI framework that leverages 3D tissue morphology and minimal 2D ST to predict volumetric 3D ST. By pretraining on diverse 3D morphology-transcriptomic pairs from heterogeneous tissue samples and then fine-tuning on minimal 2D ST data from a specific volume of interest, VORTEX learns both generic tissue-related and sample-specific morphological correlates of gene expression. This approach enables dense, high-throughput, and fast 3D ST, scaling seamlessly to large tissue volumes far beyond the reach of existing 3D ST techniques. By offering a cost-effective and minimally destructive route to obtaining volumetric molecular insights, we anticipate that VORTEX will accelerate biomarker discovery and our understanding of morphomolecular associations and cell states in complex tissues. Interactive 3D ST volumes can be viewed at https://vortex-demo.github.io/