Long-read sequencing of an advanced cancer cohort | LC 25

Biography

Kieran is a bioinformatician staff scientist at Canada’s Michael Smith Genome Sciences Centre. He helps coordinate a range of projects using new sequencing platforms, especially Oxford Nanopore sequencing. These include personalised oncogenomics, determining parent of origin for genetic disease, de novo assembly of reference genomes, and more.

In the past, he has developed software for genome scaffolding, ontology browsing, and flow cytometry analysis, and has performed research into leukaemia biology and diagnosis using a wide range of biological data.

Abstract

The Long-Read Personalized OncoGenomics (POG) dataset comprises a cohort of 189 patient tumors and 41 matched normal samples sequenced using the Oxford Nanopore Technologies PromethION platform. This dataset from the POG program and the Terry Fox Research Institute’s Marathon of Hope Cancer Centres Network (MOHCCN) includes DNA and RNA short-read sequence data, analytics, and clinical information.

We studied the potential of long-read sequencing for resolving complex cancer-related structural variants, viral integrations, and extrachromosomal circular DNA. Long-range phasing facilitated the discovery of allelically differentially methylated regions (aDMRs) and allele-specific expression, including recurrent aDMRs in the cancer genes RET and CDKN2A. MLH1 germline promoter methylation was directly observed in Lynch syndrome. BRCA1 and RAD51C promoter methylation was shown to be a likely driver of homologous recombination deficiency in cases where no coding driver mutation was found.

This dataset demonstrated applications for long-read sequencing in precision cancer medicine and is available as a resource for developing analytical approaches using long-read technology. The long-read POG dataset is available in the European Genome-phenome Archive (EGA), and forms part of the MOHCCN Gold Cohort resource. PromethION sequencing of new POG cases is ongoing, where material is available, and will serve as an adjunct to conventional short-read whole-genome and transcriptome analysis.