Pediatric B-ALL Bionano data

To capture the structural variant landscape more thoroughly in the human genome, we developed an integrated pipeline that combines Bionano OGM and Illumina whole genome sequencing and applied it to samples from 29 pediatric B-ALL patients. Structural variants drive tumorigenesis by disrupting normal gene function through insertions, inversions, translocations, and copy-number changes including deletions and duplications. Detecting structural variants is crucial to revealing their role in tumor development, clinical outcomes, and personalized therapy. Presently, most studies rely on short-read data from next-generation sequencing that align back to a reference genome to determine if and, if so, where a structural variant occurs. However, structural variant discovery by short-read sequencing is challenging, due primarily to the difficulty of mapping in regions of repetitive sequences. Optical genome mapping (OGM) is a recent technology for imaging and assembling long DNA strands to detect structural variation. The addition of OGM allowed us to identify 511 deletions, 506 insertions, 93 duplication/gains, and 145 translocations that were otherwise missed in short-read data. Moreover, we identified several novel gene fusions, whose expression we confirmed by RNA sequencing. Our results highlight the benefit of integrating OGM and short-read detection methods to obtain a comprehensive analysis of the genetic variation that can aid in clinical diagnosis, provide new therapeutic targets, and improve personalized medicine in cancers driven by structural variation.