RARE Daily

Oxford Nanopore Enters Collaboration with German Medical Centers to Improve Diagnoses of Genetic Diseases

June 12, 2023

Rare Daily Staff

Oxford Nanopore Technologies said it entered into a research collaboration agreement with the Clinical Long-read Genome Initiative, a new national German program developed to evaluate the clinical and research applications of comprehensive nanopore-based sequencing to advance the understanding of rare disease.

Scientists within four German research university medical centers will use Oxford Nanopore’s technology to evaluate the advantages of technology that can sequence any length DNA fragments, from short to ultra-long, when establishing firm genetic disease characterization. The universities will study a multi-center cohort of patients with unsolved rare diseases, such as neurological, neurodevelopmental, and imprinting disorders.

The two-year pilot study will explore the benefits and feasibility of nanopore-based genome sequencing in German clinical practice, with a broader aim to provide a blueprint for implementation across Germany’s sequencing centers.

The work is expected to be performed on devices capable of running up to 24 flow cells at once and is designed to enable accelerated sequencing and to deliver ultra-rapid analysis. This will enable the researchers to identify different classes of disease-causing variants simultaneously using the latest high-accuracy chemistry, including single nucleotide variations, structural variations, and also methylation, all in one assay.

“We believe that the introduction of long-read genome sequencing into clinical routine will allow us to further close the diagnostic gap in patients with monogenic diseases,” said Nadja Ehmke, head of clinical genomics unit at the Institute of Medical and Human Genetics, Charité—Universitätsmedizin Berlin. “For the first time, we can sequence complex regions, determine structural variants and perform haplotype-based analyses. In addition, detection of methylation patterns is possible. This allows us to better understand disease mechanisms and develop therapies.”

The study builds on structured diagnostic processes established and evaluated within a three-year prospective study in Germany that involved more than 200 clinicians and scientists and was designed to assess the clinical value of exome sequencing in the ultra-rare disease population. That study, known as TNAMSE, was completed using short-read sequencing technology.

Oxford Nanopore said its technology is well suited to serve Long-read Genome Initiative’s (lonGER) aim of improving clinical outcomes by using its ability to sequence any-length fragments of DNA from short to ultra long. This has been shown to demonstrate specific advantages over short reads in the study of genetic diseases.

The long read capabilities of nanopore sequencing enable phasing of genetic variants, which is important for clinical interpretation of the genome in terms of identifying compound heterozygous variants and parental origin. It is also able to resolve “dark” regions that cannot be accessed by short reads, which accounts for up to 8 percent of the genome and could contain clinically relevant variants. Long nanopore sequencing reads are also able to resolve SVs much more comprehensively – historically an important yet understudied type of human genetic variation as it has been challenging for traditional sequencing technologies.

“Oxford Nanopore’s any read length sequencing technology shows that what you’re missing matters as it can deliver comprehensive insights across the whole genome,” said Gordon Sanghera, CEO, Oxford Nanopore Technologies. “Together with the lonGER consortium, we can unlock the potential of nanopore sequencing technology to drive breakthrough discoveries and transform the lives of those affected by these rare diseases.”

Photo: Gordon Sanghera, CEO of Oxford Nanopore Technologies

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