JuLI: accurate detection of DNA fusions in clinical sequencing for precision oncology

Abstract Accurate detection of genomic fusions by high-throughput sequencing in clinical samples with inadequate tumor purity and formalin-fixed, paraffin embedded tissue is an essential task in precise oncology. We developed the fusion detection algorithm Junction Location Identifier for optimization of high-depth clinical sequencing. Novel filtering steps were implemented to minimize false positives in clinical setting. The algorithm was comprehensively validated using high-depth sequencing data from cancer cell lines and clinical samples and genome sequencing data from NA12878. Junction Location Identifier showed improved performance mainly in positive predictive value over state-of-the-art fusion callers in cases with high-depth clinical sequencing and rescued a driver fusion from false negative in plasma cell-free DNA using joint calling.