Long-read transcriptome analysis using IsoRanker for identifying pathogenic variants in Mendelian conditions

Cheng et al. introduce IsoRanker, a long-read transcriptome sequencing-based framework that prioritizes functionally relevant variants by detecting genes and isoforms with outlier expression, allelic imbalance, and/or nonsense-mediated decay (NMD). Applied to a cohort of undiagnosed individuals, IsoRanker deprioritized prior candidates and enabled pathogenic variant discovery and precision treatment.