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Detection of alternative isoforms of gene fusions using long-read Nanopore RNA-seq


Gene fusions are the result of chromosomal rearrangement and other structural variants. They can be detected in RNA-seq as chimeric transcripts. They can be important cancer drivers and drug targets. It is difficult to identify gene fusions from short-read (Illumina) data. Very few of the reads will cross the fusion breakpoint. Lots of noise from other mismapping reads. Long read sequencing (nanopore, pacBio) can capture whole transcripts. More sequence around the fusion point allows for more confident fusion detection. Also allows for better alternative splicing and full-length isoform identification. The ability to detect alternative splicing in fusions is novel and clinically relevant. Alternative splicing has been shown to be a method for developing resistance to drugs targeting gene fusions. We have developed FLAIR-Fusion, a computational tool to identify gene fusions and their full-length isoforms

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