Oxford Nanopore sequencing technology will be used in a pioneering new collaboration with Genomics England, to sequence as many as 7,500 samples from participants of the landmark 100,000 Genomes Project with a range of genetic or suspected genetic disorders.
The programme aims to improve diagnostic outcomes for participants with rare conditions, including those who have not yet received a diagnosis through short-read only sequencing methods. The programme will also further aim to develop an accredited laboratory workflow and data analysis pipelines to support the clinical use of human whole genome sequence data generated using nanopore sequencing.
The study will use nanopore whole genome sequencing for three distinct objectives: to uncover new diagnoses in participants who have yet to be diagnosed, to finalise genetic characterisation and heritability within families for partially diagnosed participants. And finally to identify potentially missed variants and highlight improvements over other, short-read-only technology. The ultimate goal of this proof-of-concept study will be to generate datasets that characterise improvements in insights using nanopore sequencing. The dataset will also be of great value in any disease where genetics plays a role, including common diseases, enabling researchers to look easily in the one dataset to study how genetic variation can influence health and disease.
This project will be part of a wider multiomic study led by Genomics England – including genomic, transcriptomic, epigenetic, proteomic and metabolomic analysis - to support the understanding of multiomic research in rare cases that are difficult to resolve. Whole genome sequencing will be performed on all samples and a subset will also have full-length RNA sequencing, made possible by Oxford Nanopore technology’s ability to sequence fragments of any length. The sample cohort will be inclusive of singleton samples and duo/trio families.
Eurofins Genomics will be the service provider for the sequencing, in the UK. Eurofins Genomics brings a rich legacy of managing extensive population genomic initiatives across the globe, employing cutting-edge sequencing and predictive genomics methodologies. The incorporation of long-read, high-throughput capabilities will significantly expedite the integration of long-read technologies in both diagnostic and applied sectors. This advancement is set to be fortified by the commencement of procedures aimed at securing clinical accreditation for the pipeline.
The project will use Oxford Nanopore’s high-throughput sequencing device, the PromethION 48, which provides rapid characterisation of large genomes, delivering scalability for large projects with low infrastructure requirements. Combined with the latest “Q20+” chemistry, comprised of Kit 14 and R10.4.1 flow cells, Oxford Nanopore delivers complete and accurate genomic data, at scale.
Once the project is complete, the data will be stored in the National Genomic Research Library, creating the world's largest global dataset with genetic and epigenetic profiling for rare disease.
Gordon Sanghera, CEO, Oxford Nanopore Technologies, commented: “We are delighted to be extending our collaboration with Genomics England into rare disease research, in addition to our current cancer programmes. The combination of very high single-molecule accuracy with the ability to reach all parts of the genome and characterise all types of genetic variation, mean that nanopore sequencing can deliver comprehensive whole genome analysis and will reveal that what’s missing matters.”
