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This research demonstrates that adversarial fine-tuning of foundation models can effectively translate between unpaired spatial transcriptomics and single-cell RNA sequencing data, overcoming the scarcity of paired datasets. By recovering spatial neighborhood information from dissociated cells, the method outperforms existing multi-omics translation approaches, offering a scalable solution for high-resolution tissue analysis. The work bridges computational biology and AI, leveraging foundation models to address limitations in subcellular gene profiling.
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Single-Cell Cross-Modal Transfer by Adversarial Fine-Tuning of Foundation Models

arXiv2 min read

arXiv:2606.07676v1 Announce Type: cross Abstract: Spatial transcriptomics (ST) is a powerful tool for exploring biological properties dependent on structure, proximity, and interaction in tissue. The methods underpinning ST are developing rapidly but are limited in their ability to profile many thousands of genes at a subcellular scale. Although dissociated from tissue, it is known that the whole-transcriptome readouts of cells in single-cell RNA sequencing (scRNA-seq) retain information about their former in situ neighbourhoods, motivating computational methods to recover it. While paired ST and scRNA-seq datasets are scarce, each modality in its own right is abundantly available. We therefore propose to perform cross-modal translation between unpaired ST and scRNA-seq data. In this work we show that a single-cell foundation model can perform this translation via adversarial fine-tuning. We demonstrate that our method performs favourably against methods built for multi-omics translation.

Abstract:Spatial transcriptomics (ST) is a powerful tool for exploring biological properties dependent on structure, proximity, and interaction in tissue. The methods underpinning ST are developing rapidly but are limited in their ability to profile many thousands of genes at a subcellular scale. Although dissociated from tissue, it is known that the whole-transcriptome readouts of cells in single-cell RNA sequencing (scRNA-seq) retain information about their former in situ neighbourhoods, motivating computational methods to recover it. While paired ST and scRNA-seq datasets are scarce, each modality in its own right is abundantly available. We therefore propose to perform cross-modal translation between unpaired ST and scRNA-seq data. In this work we show that a single-cell foundation model can perform this translation via adversarial fine-tuning. We demonstrate that our method performs favourably against methods built for multi-omics translation.

Genomics (q-bio.GN); Artificial Intelligence (cs.AI)

arXiv:2606.07676 [q-bio.GN]

(or arXiv:2606.07676v1 [q-bio.GN] for this version)

https://doi.org/10.48550/arXiv.2606.07676 Focus to learn more arXiv-issued DOI via DataCite (pending registration)

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Full text under the publisher's open licence · 230 words

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