Advancing automated cell type annotation with large language models and single-cell isoform sequencing

Accurate cell type identification is critical for interpreting single-cell transcriptomic data and understanding complex biological systems. In this review, we discuss how natural language processing and large language models can enhance the accuracy and scalability of cell type annotation. We also highlight how emerging single-cell long-read sequencing technologies enable isoform-level transcriptomic profiling, offering higher resolution than conventional gene expression-based methods and providing opportunities to redefine cell types. By integrating the insights of key technical and algorithmic advances across sequencing and computational approaches, we provide a unified overview of recent developments that are reshaping automated cell type annotation and improving the precision of biological interpretation.