Using deep long-read RNAseq in Alzheimer's disease brain to assess clinical relevance of RNA isoform diversity.

Due to alternative splicing, human protein-coding genes average over eight RNA isoforms, resulting in nearly four distinct protein coding sequences per gene. Long-read RNAseq (IsoSeq) enables more accurate quantification of isoforms, shedding light on their specific roles. To assess the clinical relevance of measuring RNA isoform expression, we sequenced 12 aged human frontal cortices (6 Alzheimer's disease cases and 6 controls, 50% female) using one Oxford Nanopore PromethION flow cell per sample. Our study uncovered 53 new high-confidence RNA isoforms in clinically relevant genes, including several where the new isoform was one of the most highly expressed for that gene. Specific examples include

Déclaration de conflit d'intérêts

Competing interests The authors report no competing interests.