Understanding the LLM-based gene embeddings

Cai, Y.; Gan, D.; Zhang, H.; Li, J.

doi:10.64898/2025.12.19.695582

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bioRxiv · 10.64898/2025.12.19.695582

Understanding the LLM-based gene embeddings

Cai, Y.·Gan, D.·Zhang, H.·Li, J.

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Abstract

Large language model (LLM)-derived gene embeddings, generated from brief NCBI gene descriptions, have shown strong performance in recent biological applications, yet the biological information they contain remains unclear. We evaluate these embeddings using a Gene Set Enrichment Analysis (GSEA)-based framework that treats each embedding dimension as a potential carrier of pathway-level information. OpenAIs embeddings recover over 93% of Hallmark and C2 pathways, with pathway signals distributed across many dimensions. Even embeddings generated from gene symbols alone recover more than 64% of pathways, indicating substantial prior biological knowledge embedded in the model. Comparing 11 small language models reveals that domain-specific models perform best with minimal input, but all models approach OpenAI-level coverage when given modest textual context. Collectively, these results show that LLM-derived embeddings encode unexpectedly extensive pathway-level information, supporting their use as lightweight, informative representations for downstream biological analysis.

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Cai, Y., Gan, D., Zhang, H., Li, J.. 2025-12-22. Understanding the LLM-based gene embeddings. https://doi.org/10.64898/2025.12.19.695582

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