Translating long-read sequencing into a scalable NHS bioinformatics workflow | LC26

Abstract
The North Thames Genomic Laboratory Hub is one of seven hubs providing National Health Service (NHS) genomic testing, including specialist testing for 14 disease areas for half of England. The Bioinformatics team develops pipelines to interpret complex genomic data, enabling clinical scientists to identify disease-causing variants and deliver diagnoses that support personalised care, family planning, and access to targeted therapies. Long-read sequencing can improve diagnostic yield by resolving low complexity and repetitive regions, enhancing structural variant detection, and enabling phasing. However, clinical workflows and expertise are centred around short-read technologies. This project aimed to develop and integrate an Oxford Nanopore Technologies long-read sequencing pipeline into the existing clinical workflow. We developed a flexible long-read analysis framework supporting trio and singleton genome sequencing, virtual panels, targeted amplicon, and adaptive sequencing. Dedicated workflow ‘arms’ for each test type are embedded within the clinical system, with GitLab version control ensuring auditability. Automated execution via standardised sample sheets, run naming, and configuration files enable integration with existing workflow management. Analyses follow EPI2ME recommendations, and outputs feed directly into our bespoke tertiary analysis package, which offers configurable filtering modes. Results are presented within our in-house variant interpretation platform, allowing scientists to review long-read data alongside short-read outputs in a familiar interface. This integrated approach streamlines accreditation, provides control over release cycles, maintains robust data governance, and removes the need for scientists to learn new tools or work across multiple platforms. The framework establishes a scalable foundation for rapidly translating emerging long-read methods into NHS service.

Biography
Ashley Pritchard is a Health and Care Professions Council (HCPC) registered Senior Translational Bioinformatician at the NHS North Thames Genomic Laboratory Hub, with a research background and PhD in cancer genomics and over eight years of clinical experience. She is currently funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre to bridge research and clinical service delivery by translating emerging genomic technologies into NHS practice. Her current focus is on implementing long-read sequencing technologies with demonstrated clinical utility, integrating them into routine diagnostics to enhance workflows and improve patient care.