Bridging Large Language Models and Single-Cell Transcriptomics in Dissecting Selective Motor Neuron Vulnerability

Understanding cell identity and function through single-cell level sequencing data remains a key challenge in computational biology. We present a novel framework that leverages gene-specific textual annotations from the NCBI Gene database to generate biologically contextualized cell embeddings. For each cell in a single-cell RNA sequencing (scRNA-seq) dataset, we rank genes by expression level, retrieve their NCBI Gene descriptions, and transform these descriptions into vector embedding representations using large language models (LLMs). The models used include OpenAI text-embedding-ada-002, text-embedding-3-small, and text-embedding-3-large (Jan 2024), as well as domain-specific models BioBERT and SciBERT. Embeddings are computed via an expression-weighted average across the top N most highly expressed genes in each cell, providing a compact, semantically rich representation. This multimodal strategy bridges structured biological data with state-of-the-art language modeling, enabling more interpretable downstream applications such as cell-type clustering, cell vulnerability dissection, and trajectory inference.

@article{jiang2025_2505.07896,
  title={ Bridging Large Language Models and Single-Cell Transcriptomics in Dissecting Selective Motor Neuron Vulnerability },
  author={ Douglas Jiang and Zilin Dai and Luxuan Zhang and Qiyi Yu and Haoqi Sun and Feng Tian },
  journal={arXiv preprint arXiv:2505.07896},
  year={ 2025 }
}