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

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.