Multimodal learning enables chat-based exploration of single-cell data

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Abstract

Single-cell sequencing characterizes biological samples at unprecedented scale and detail, but data interpretation remains challenging. Here, we present CellWhisperer, an artificial intelligence (AI) model and software tool for chat-based interrogation of gene expression. We establish a multimodal embedding of transcriptomes and their textual annotations, using contrastive learning on 1 million RNA sequencing profiles with AI-curated descriptions. This embedding informs a large language model that answers user-provided questions about cells and genes in natural-language chats. We benchmark CellWhisperer’s performance for zero-shot prediction of cell types and other biological annotations and demonstrate its use for biological discovery in a meta-analysis of human embryonic development. We integrate a CellWhisperer chat box with the CELLxGENE browser, allowing users to interactively explore gene expression through a combined graphical and chat interface. In summary, CellWhisperer leverages large community-scale data repositories to connect transcriptomes and text, thereby enabling interactive exploration of single-cell RNA-sequencing data with natural-language chats.

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Schaefer, M., Peneder, P., Malzl, D., Lombardo, S. D., Peycheva, M., Burton, J., … Bock, C. (2025). Multimodal learning enables chat-based exploration of single-cell data. Nature Biotechnology. https://doi.org/10.1038/s41587-025-02857-9

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