Next-generation sequencing (NGS) has become the primary technology for discovering gene fusions. Decreasing NGS costs have resulted in a growing quantity of patients with whole transcriptome sequencing (RNA-seq) and whole genome sequencing (WGS) data. We developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read alignment. INTEGRATE has become widely adopted by the larger cancer research community to discover biologically and clinically relevant gene fusions. Here we explain the rationale driving the development of the INTEGRATE tool and describe the detailed practical procedures for applying INTEGRATE to discover gene fusions using NGS data. INTEGRATE can be applied to both combined data and RNA-seq only data.
Keywords: Cancer; Chimeras; Gene fusion; Next-generation sequencing; RNA-seq; Structural variation; Whole transcriptome sequencing; Whole-genome sequencing.