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

Abstract

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 corresponding NCBI gene descriptions, and transform these descriptions into vector embedding representations using large language models (LLMs). The models used include OpenAI's text-embedding-ada-002, textembedding-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.

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