Long-read whole-transcriptome sequencing and selective gene panel profiling enable sensitive detection of fusion oncogenes in pediatric B-cell acute lymphoblastic leukemia

Long-read whole-transcriptome sequencing (WTS) has the potential to precisely characterize fusion oncogenes that drive leukemia and other cancers. While there are a variety of general-purpose fusion detection algorithms that use modern long-read sequencing data, they show poor sensitivity for precision diagnostics in B-ALL and do not robustly assess technical and analytical parameters (ex. sequencing depth) to reliably detect fusion transcripts. FUSILLI (FUSions In Leukemia Long-read sequencing Investigator) is a novel long-read fusion detection algorithm, with a focus on targeted genomic subtyping in B-ALL.