NIH Alzheimers study shows scaled, accurate data

RNS Number : 7196V

Oxford Nanopore Technologies plc

11 April 2023

 

11 April 2023

Oxford Nanopore Technologies plc

Announces NIH Center for Alzheimer's and Related Dementias publication showing comprehensive, high accuracy nanopore-based sequencing approach

Oxford Nanopore Technologies plc (LSE: ONT) ("Oxford Nanopore"), the company delivering a new generation of Nanopore-based molecular sensing technology, today announces the publication of a preprint from a team led by researchers at the NIH Center for Alzheimer's and Related Dementias (CARD), the University of California, Santa Cruz and the National Cancer Institute. This group has developed a protocol for highly accurate whole human genome sequencing, at scale, that provides a comprehensive view of haplotype-resolved variation ( the identification and characterisation of genetic variations specific to chromosome haplotypes - the specific combination of genetic variations on a single chromosome that are inherited together from one parent) and methylation (chemical modification of native DNA). In the preprint, the team describes how the protocol makes large-scale, long, native DNA sequencing projects feasible due to the lower cost and higher throughput of Oxford Nanopore's PromethION device, when compared with alternative sequencing methods. The CARD initiative supports basic, translational, and clinical research on Alzheimer's disease and related dementias.

Using a single PromethION flow cell with the latest version of Oxford Nanopore's 'Q20+ chemistry', the team stated, "we can detect SNPs with F1-score better than ...short read sequencing" and "further, we can discover structural variants with F1-scores comparable to state-of-the-art methods involving [alternative long read sequencing] and trio information (but at lower cost and greater throughput)".

The results with Oxford Nanopore's R10 flow cells included SNP recall/precision of 0.9979/0.998, SV accuracy 0.9764/0.9835 and significant improvements to indel accuracy to 0.9948/0.9748 in coding regions. The study protocol is currently being used to sequence thousands of brain-based human genomes as a part of the NIH CARD initiative. 

The study showed that the latest R10.4.1 flow cells significantly improve reference-based indel calling, which is vital for small variant calling which, in regions not containing homopolymers or tandem repeats, achieves an F1-score of 0.997. The paper also describes how with nanopore-based phasing, it is possible to combine and phase small and structural variants at megabase scales, all of which combines to give the clearest picture yet of the whole genome when studying samples relating to Alzheimer's and related dementias.

Base modifications provide critical insights into many biological questions and the paper states how methylation calls "were highly concordant with the standard bisulfite sequencing", but in addition they could produce reliable haplotype-resolved methylation calls for even greater insight. The methylation data is produced during a standard sequencing run and without additional cost and complexity that is required for bisulphite sequencing, rather than as a result of a separate process.  

The team used Oxford Nanopore's high-throughput sequencing device, the PromethION 48, which is capable of sequencing over 4900[i] genomes per year delivering scalability for large projects. Combined with the latest chemistry, Kit 14 and R10.4.1 flow cells, Oxford Nanopore now delivers the most complete and accurate genomic data, at scale. This combines very high single-molecule accuracy with the ability to reach all parts of the genome and characterise all types of genetic variation, through the ability to sequence any length fragments of native DNA/RNA. 

Gordon Sanghera, CEO, Oxford Nanopore Technologies, commented: 

"We are delighted to see this latest work from the NIH CARD team, whose approach demonstrates breakthrough accuracy with Oxford Nanopore's newest Q20+ chemistry and the R10 nanopore, whilst using the same platform. This shows that Oxford Nanopore now delivers comprehensive and accurate genomic data, at scale. We congratulate all the fantastic scientists who have contributed a huge amount to this significant project. 

"Furthermore it is fantastic to see this protocol being used in the CARD programme's work in Alzheimer's disease. As the paper states, a substantial part of the variation in the human genome is not accessible with short-reads, so we know that what is missing matters. We look forward to seeing the outcomes and impact of the CARD programme in due course." 

[ENDS]

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About Oxford Nanopore Technologies plc:

Oxford Nanopore Technologies' goal is to bring the widest benefits to society through enabling the analysis of anything, by anyone, anywhere. The company has developed a new generation of nanopore-based sensing technology that is currently used for real-time, high-performance, accessible, and scalable analysis of DNA and RNA.  The technology is used in more than 120 countries, to understand the biology of humans, plants, animals, bacteria, viruses and environments as well as to understand diseases such as cancer.  Oxford Nanopore's technology also has the potential to provide broad, high impact, rapid insights in a number of areas including healthcare, food and agriculture. 

For more information please visit: www.nanoporetech.com

Forward-looking statements

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About CARD

Stimulating and Accelerating Alzheimer's and Related Dementias Research at NIH

Through NIH's Center for Alzheimer's and Related Dementias (CARD), researchers work across scientific domains and disease boundaries to bridge basic, preclinical, and clinical research with the goal of accelerating translational research on these devastating diseases. CARD is a collaborative initiative of the National Institute on Aging and the National Institute of Neurological Disorders and Stroke that supports basic, translational, and clinical research on Alzheimer's disease and related dementias. CARD's central mission is to initiate, stimulate, accelerate, and support research that will lead to the development of improved treatments and preventions for these diseases.
For more information please visit: https://card.nih.gov/about-card

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[i] 4,900 genomes per year assumes sequencing one genome per flow cell across all 48 flow cells, twice a week for 52 weeks a year.  Users may choose to sequence two genomes per flow cell for twice the capacity.

 

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