GenePT: A Simple But Effective Foundation Model for Genes and Cells Built From ChatGPT
Abstract
There has been significant recent progress in leveraging large-scale gene expression data to develop foundation models for single-cell biology. Models such as Geneformer and scGPT implicitly learn gene and cellular functions from the gene expression profiles of millions of cells, which requires extensive data curation and resource-intensive training. Here we explore a much simpler alternative by leveraging ChatGPT embeddings of genes based on literature. Our proposal, GenePT, uses NCBI text descriptions of individual genes with GPT-3.5 to generate gene embeddings. From there, GenePT generates single-cell embeddings in two ways: (i) by averaging the gene embeddings, weighted by each genes expression level; or (ii) by creating a sentence embedding for each cell, using gene names ordered by the expression level. Without the need for dataset curation and additional pretraining, GenePT is efficient and easy to use. On many downstream tasks used to evaluate recent single-cell foundation models -- e.g., classifying gene properties and cell types -- GenePT achieves comparable, and often better, performance than Geneformer and other models. GenePT demonstrates that large language model embedding of literature is a simple and effective path for biological foundation models.
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Abstract summary
Claude Opus 5.5 · xhigh effort · 2 Nov 2026 · from the abstract · CC BY-NC-ND 4.0
GenePT embeds National Center for Biotechnology Information (NCBI) gene text descriptions using GPT-3.5 and aggregates them by expression to represent single cells without pretraining on millions of transcriptomes.
Single-cell foundation models such as Geneformer and scGPT learn gene and cell representations from expression profiles of millions of cells, requiring extensive dataset curation and compute-intensive pretraining. GenePT avoids expression-based pretraining by using GPT-3.5 embeddings of literature-based gene descriptions and combining them with single-cell expression levels.
Key results
ShownWithout expression dataset curation or additional model pretraining, GenePT matches or outperforms single-cell foundation models such as Geneformer on downstream gene-level and cell-level classification tasks.
Evaluated on gene property classification and cell type classification tasks against Geneformer and other models (quantitative performance metrics and dataset counts are not reported in the abstract). · Abstract
Methods, data and reproducibility
GenePT generates gene-level embeddings from National Center for Biotechnology Information (NCBI) text descriptions using GPT-3.5, then constructs single-cell embeddings either by taking an expression-weighted average of gene embeddings or by embedding a sentence of gene names ranked by expression level.
- National Center for Biotechnology Information (NCBI) text descriptions of individual genes
- Methods & tools
- GenePT, ChatGPT, GPT-3.5, NCBI, Geneformer, scGPT
Limitations (2)
- The abstract does not provide quantitative evaluation metrics, dataset details, or links to code and precomputed embeddings. · noted in this summary
- Gene representations rely on existing NCBI literature descriptions, which may be sparse for poorly annotated genes. · noted in this summary
Who should read:Read this if you use or benchmark single-cell foundation models like Geneformer or scGPT and want a training-free baseline built from GPT-3.5 gene text embeddings.
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