SpaFactor: Lightweight Spatial Context-Aware Gene Program Modeling for Histology-to-Transcriptomics Inference

SpaFactor is a lightweight framework that predicts spatial gene expression from hematoxylin and eosin images by fusing central spot visuals with multiscale neighborhood context. It uses a residual MLP to map tissue microenvironment to low‑dimensional latent gene programs, which are decoded into coordinated multi‑gene predictions. Across five public cohorts, SpaFactor outperforms existing methods, especially for spatially variable genes, and better recovers biologically organized spatial patterns.

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