Oxford Nanopore announces breakthrough technology performance to deliver complete human genome assemblies and richer multiomic data in London Calling tech update

Enhancing customer support and accelerating end-to-end workflow adoption
Rosemary Sinclair Dokos, SVP of Product and Programme Management, took the stage at London Calling on Thursday to share an update on the Company’s product and workflow roadmap. Community collaboration and feedback is critical to Oxford Nanopore’s success. During Rosemary’s talk, she spoke about how this crucial feedback is incorporated into the product roadmap and aims to drive improvements to the user experience. In addition, Rosemary spoke about their growing portfolio of end-to-end workflows, which then feeds the Company’s clinical roadmap as Oxford Nanopore accelerates its regulated product pipeline.

Supporting our users:

Over the past 12 months, Oxford Nanopore has doubled the number of support staff and significantly increased product testing resources. Customer feedback has been heard loud and clear, and the Company’s expansion in this area will deliver faster and more efficient support. By strengthening support teams and enhancing product testing capabilities, Oxford Nanopore aims to provide a seamless and robust user experience, reinforcing its dedication to customer satisfaction.

Progress made to Oxford Nanopore’s clinical roadmap:

Oxford Nanopore continues to make significant strides in its regulated product pipeline.

The GridION Q-Line product range is on track to launch shortly in Q3-2024.

The GridION is on track to meet ISO 13485 standards during 2025, and the company will pursue CE-IVD certification in the EU thereafter. This device will initially be available to specified partners, enhancing clinical capabilities.

In addition, the ElysION, which is now in early access, has already begun its journey towards becoming a regulated device enabling a fully automated sample-to-answer solution for future clinical applications, showcasing the company’s ongoing commitment to expanding and supporting advanced research and diagnostic applications.

Breakthrough technology performance to deliver complete human genome assemblies and richer multiomic data
Oxford Nanopore Chief Technology, Innovation and Product Officer Clive G Brown announced breakthrough performance data and new platform updates in his technology update at the company’s annual London Calling conference, held between 21 and 24 May 2024. The talk launched the nanopore-only telomere-to-telomere (T2T) genome assembly product bundle, making this breakthrough method more accessible.

In addition, Clive showed a glimpse of what may be possible in the future with the sequencing of a whole T2T yeast chromosome in a single read for the first time. Further improvements in direct RNA sequencing accuracy and yield, and pipelines for ultra-high output sequencing, including a potential route to a 15-minute human genome, were shared.

Building on the distinctive advantages of the Oxford Nanopore platform, these advancements deliver highly accurate, information-rich data, faster insights, at any scale for both DNA and RNA sequencing applications. Oxford Nanopore’s technology continues to evolve to meet the growing demand for accessible, real-time analysis and open new possibilities in research, clinical and industrial settings.

Watch the tech talk or read the summary below for more information on Oxford Nanopore’s technology pathway to address these current and future needs.
Technology updates included:
Delivering increasingly rich, high performance multiomic data: Continuous improvement to performance and rich data generation are driving increasingly comprehensive and accurate genomic, transcriptomic and epigenetic information about human and non-human organisms.

Increased accuracy: Oxford Nanopore has initiated its migration to transformer model basecalling architecture, which is improving performance for single molecule accuracy, now reaching Q26 at 400bps (99.75% simplex accuracy). In addition to improved basecalling, the update also highlighted the release of the nanopore 6B4 polishing chemistry delivering Q50 nanopore-only human telomere-to-telomere (T2T) assemblies. Beyond basecalling the team showed improvements to variant detection algorithms and read polishing methods that are developed with external collaborators.

Richer data: The Company highlighted improvements to its machine learning model to enable real-time, high-accuracy epigenetic insights in all contexts, including plants and bacteria, delivering on the promise to sequence the most common DNA modifications in any genome. Improved accuracy was reported for calling 5mC (5-methylcytosine), 5hmC (5-hydroxymethylcytosine), and 6mA (N6-methyladenine) modifications. For the first time, the Company also announced the release of a 4mC (4-Methylcytosine) model in Dorado.

For the first time, Clive announced the ability to detect damaged DNA bases, including genomic Uracil (dU) at 96.34% accuracy, which could be helpful in monitoring response to cancer therapies.

Complete genomes with nanopore-only Telomere-to-Telomere (T2T) sequencing: Oxford Nanopore announced the release of a new, all-in-one telomere-to-telomere sequencing bundle, enabling T2T sequencing of human genomes without the need for other technologies. The capability to produce T2T assemblies addresses the gaps left by traditional sequencing methods, facilitating more comprehensive studies of complex genomic regions such as centromeres and telomeres. The new T2T bundle, which can sequence six human genomes, integrates ultra-long sequencing, Pore-C and Assembly Polishing Kit (APK) to achieve highly accurate Q50 whole human genome assemblies.

As part of Oxford Nanopore’s mission to enable the most comprehensive human genomes, the Company announced a pathway to sequencing whole T2T human genomes on a single flow cell, through improvements to output and by removing homopolymer errors with new pore chemistries

Full-length chromosomes in a single read: As the Company continues to push the boundaries of what’s possible, Clive demonstrated progress towards sequencing full-length human chromosomes in one read. He illustrated successful T2T reads of four yeast chromosomes as a proof of concept.

Improving direct RNA sequencing to support breakthrough science and biopharma workflows: Advancements in direct RNA sequencing not only enhance the accuracy and efficiency of nanopore-based RNA analysis but also open new possibilities for RNA-based research and therapeutic applications. Oxford Nanopore is the first to enable direct sequencing of the native molecule, revealing more biology including RNA base modifications. Improving RNA sequencing technology ensures that researchers have the tools they need to explore the complexities of RNA biology and develop innovative RNA-based treatments.

Higher accuracy and output for direct RNA sequencing: Following the successful launch of Oxford Nanopore’s latest RNA004 chemistry last year, the Company showcased continual increases in direct RNA sequencing accuracy. Improved models in combination with the latest chemistry now achieves single molecule raw-read accuracy of 98.8% median accuracy. Improvements to run conditions protocols have also resulted in a ~20% output increase in reads over runtime, delivering around three million more total RNA reads over a 72hour run.

Short RNA sequencing now enabled: While the platform historically sequenced RNA reads of 200 nucleotides or longer, the latest improvements to scripts and software now enables sequencing RNA molecules of 50 nucleotides or more. This opens new avenues of research in RNA biology with the ability to sequence short fragments, including tRNA and degraded RNA.

Comprehensive RNA modification detection: The updated platform can now detect a broader range of RNA modifications in real-time, including m6A (N6-methyladenosine) in all contexts at 97.1% accuracy and pseudoU (pseudouridine) in all contexts at 97.6% accuracy.

Integrated, real-time mRNA vaccine QC: As one example of the power of RNA analysis, Oxford Nanopore’s platform now offers a comprehensive real-time quality control (QC) test for mRNA vaccines, combining multiple critical quality attributes into a single, efficient test. This integrated approach – which will be released on GridION with Q Line – simplifies the QC process, making it faster, simpler and more reliable. Traditional methods for mRNA vaccine QC are often time-consuming and require multiple platforms and techniques.

Simplifying products and workflows to support broader usage: To support different users taking advantage of nanopore sequencing, innovations have been introduced to simplify and make more accessible the end-to-end sequencing process. This includes simplifying data analysis through a new integration of EPI2ME into MinKNOW 6.0.

Pipeline: enabling ultra-high output and accessible, distributed sequencing for anyone, anywhere: Oxford Nanopore continues to innovate towards a new future of near-sample, real-time, low-cost technology that can characterise biological samples in any environments from clinics to factories to classrooms.

MinION Mk1D in early access: The MinION Mk1D, which offers better temperature control and a USB-C connection, will be entering early access over the summer with London Calling participants being the first to access this latest device. This integration allows users to conduct nanopore sequencing in a compact and mobile setup to support the distributed analysis of anything, anywhere.

Enhanced portability with TraxION: Announced last year, TraxION not only enables portable library prep in the field but also streamlines the sequencing process from nucleic acid extraction and library preparation to nanopore sequencing. This year the Company announced a new TraxION design to allow for sequencing in addition to library preparation in a single unit.

Voltage chip for rapid WGS: Sequencing a whole human genome in under an hour – with a potential route to a 15-minute genome – could be a possibility with the pipeline Voltage chip, a 100k-channel device that would 10x the speed of today’s 3000 channel PromethION Flow Cells. This chip is still in development.

Even smaller formats with new platforms: A new prototype of Oxford Nanopore’s smallest sequencer to date – the “SmidgION ASIC” – was on display in London Calling’s Live Lounge. This tiny sequencer is the latest device to incorporate the new, small and low power chip (application specific integrated circuit – ASIC), which is underpinning a new family of lower-cost, lower-power devices including the multiple flow cell MkII range of instruments.

Higher output improvements: By improving buffers and conditions, the output of a PromethION Flow Cell is undergoing an upgrade; for example, 35kb reads will now yield significantly more output per flow cell, making way for two genomes per flow cell.

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