Hypatia: Comparative Isoform Profiling Across Cell Populations from Long-Read Single-Cell Transcriptomes

High-throughput long-read single-cell RNA-sequencing enables isoform-level study across single cells, yet methods for systematically assessing cell-to-cell variations remain limited. Here, we develop Hypatia, a comprehensive platform for dissecting isoform complexities across cell populations, devising Tsallis entropy and Cramer’s V to facilitate robust comparative profiling. Hypatia revealed prominent isoform species variations and usage shifts across cell-types in glioblastoma, renal cell carcinoma, and heart, highlighting clinically relevant applications for studying isoform-derived, cell-specific functions.