Short and Long-read Sequencing Applications in Oncology and Rare Disease

Fifty years ago, at the time of New England Biolabs (NEB) establishment, novel biochemistry methods were being developed to determine nucleotide sequences in DNA. Today, whole genome sequencing is routinely performed at scale and has revolutionized all areas of life science. I will describe short and long-read sequencing technologies provided by Canada’s Michael Smith Genome Sciences Centre and their utility for treatment planning in precision oncology and diagnosis of rare genetic disorders in infants. The Personalized OncoGenomics (POG) program at BC Cancer has enrolled 2,000 late-stage cancer patients and deployed whole genome and transcriptome analyses to rapidly profile somatic DNA variants and RNA expression to inform treatment planning. We have recently added third-generation nanopore long-read sequencing to better characterize large structural variants and detect epigenetic modifications such as DNA methylation directly. As in oncology, making an accurate diagnosis in rare genetic disease of infants can profoundly influence clinical management. Long-read genome sequencing has the potential for greater diagnostic sensitivity and shorter turnaround time to disease diagnosis. The RapidOmics project is evaluating long-read sequencing of acutely ill infants cared for at BC Children’s Hospital. Impactful progress has been made in these projects, facilitated by partners including NEB.