A vision foundation model for single-cell biology via spatial gene cartography

Abstract

Most single-cell foundation models are adapted from language models, representing each cell as a sequence of gene tokens. This discards the relationships among genes and often the magnitude of their expression. We present scVision, a vision foundation model that instead renders each cell as a continuous image. Using optimal transport, it places genes at fixed positions on a single shared, pan-tissue layout so that co-expressed genes become spatial neighbours, turning a transcriptome into an image in which gene programs appear as local texture. We pretrain a vision transformer by masked image modelling on 72 million human cells and use the frozen encoder with no fine-tuning. In zero-shot evaluations on six independent, held-out studies, scVision is the most accurate cell-type annotator and recovers gene programs without supervision, ahead of existing foundation models and classical baselines; on multi-study integration it matches the strongest token-based model while conserving the most biological structure, without ever seeing a batch label. Permuting the gene layout with the network fixed sharply lowers accuracy, more than removing the vision transformer itself, showing that biologically meaningful position, not the network, carries the signal. By preserving expression magnitude and gene relationships, scVision reframes single-cell representation learning as a vision problem, connecting it to the mature methods of computer vision.