Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation

N/A (targeted long-read RNA-seq, rare disease cohort)

Targeted long-read RNA-seq on genes of interest (rare disease gene panels) → splicing variant resolution with complete isoform profiles, phasing, and deep coverage of rare transcripts; applicable with low-quality samples and various tissues

Development and validation of a targeted long-read RNA-seq approach (targeted LR RNA-seq) for rare disease diagnosis and variant interpretation. The method targets clinical gene-of-interest panels, enabling deep transcript coverage with complete isoform profiles. It is applicable with low-quality RNA samples and various tissues (blood, fibroblasts). Validation on rare disease cohorts demonstrates resolution of splicing variants uninterpretable by standard methods.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Targeted LR RNA-seq is positioned as the ideal complement to LRS WGS: deeper and more informative than short-read RNA-seq for genes of interest, less expensive than whole-genome LRS RNA-seq. Targeting on clinical panels (myopathy, NDD, neuropathy panels) makes it scalable for diagnostic laboratories. An approach to watch for implementation in 2026-2027.

Science Advances (top journal) +2; gene panel targeting (clinical scalability) +2; applicable with low-quality samples +2; complementary to LRS WGS for splicing variants +2