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Towards foundation models that learn across biological scales

Kalfon, J.; Cantini, L.; Peyre, G.

2025-05-18 bioinformatics
10.1101/2025.05.16.653447 bioRxiv
Show abstract

We have reached a point where many bio foundation models exist across 4 different scales, from molecules to molecular chains, cells, and tissues. However, while related in many ways, these models do not yet bridge these scales. We present a framework and architecture called Xpressor that enables cross-scale learning by (1) using a novel cross-attention mechanism to compress high-dimensional gene representations into lower-dimensional cell-state vectors, and (2) implementing a multi-scale fine-tuning approach that allows cell models to leverage and adapt protein-level representations. Using a cell Foundation Model as an example, we demonstrate that our architecture improves model performance across multiple tasks, including cell-type prediction (+12%) and embedding quality (+8%). Together, these advances represent first steps toward models that can understad and bridge different scales of biological organization.

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