Scalable spatial transcriptomics through computational array reconstruction.

Hu, Chenlei; Borji, Mehdi; Marrero, Giovanni J; Kumar, Vipin; Weir, Jackson A; Kammula, Sachin V; Macosko, Evan Z; Chen, Fei · Nat Biotechnol · 2026

basic_science · Level V

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Abstract

Spatial transcriptomics enables gene expression mapping within tissues but is often limited by imaging constraints. We present an imaging-free approach that reconstructs spatial barcode locations using molecular diffusion and dimensionality reduction. Validated against ground truth imaging, our method achieves high fidelity and scales to centimeter-sized tissues. This approach enhances spatial transcriptomics' accessibility and throughput, enabling large-scale studies without specialized imaging equipment.

Medical subject headings