Cell2Sentence: Teaching Large Language Models the Language of Biology

Author:

Levine DanielORCID,Rizvi Syed AsadORCID,Lévy SachaORCID,Pallikkavaliyaveetil NazreenORCID,Wu Ruiming,Han InsuORCID,Zheng Zihe,Oliveira Fonseca Antonio Henrique de,Chen Xingyu,Ghadermarzi Sina,Karbasi AminORCID,Dhodapkar Rahul M.ORCID,van Dijk DavidORCID

Abstract

AbstractLarge language models like GPT have shown impressive performance on natural language tasks. Here, we present a novel method to directly adapt these pretrained models to a biological context, specifically single-cell transcriptomics, by representing gene expression data as text. Our Cell2Sentence approach converts each cell’s gene expression profile into a sequence of gene names ordered by expression level. We show that these gene sequences, which we term “cell sentences”, can be used to fine-tune causal language models like GPT-2. Critically, we find that natural language pretraining boosts model performance on cell sentence tasks. When fine-tuned on cell sentences, GPT-2 generates biologically valid cells when prompted with a cell type. Conversely, it can also accurately predict cell type labels when prompted with cell sentences. This demonstrates that language models fine-tuned using Cell2Sentence can gain a biological understanding of single-cell data, while retaining their ability to generate text. Our approach provides a simple, adaptable framework to combine natural language and transcriptomics using existing models and libraries. Our code is available at:https://github.com/vandijklab/cell2sentence-ft.

Publisher

Cold Spring Harbor Laboratory

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