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20 moments we will remember from 2020

Thu 31st December 2020

Dear all,

As each year draws to an end, we reflect on its highlights. You can read our 2019 and 2018 blogs here. But 2020 was a year like no other; it's hard to think of the following as highlights when the cause of so much of this work was so grim. However we still wanted to stop for a beat to remember the phenomenal work done in 2020 by so many people in the scientific community. As so many people enter the new year profoundly affected by COVID-19, at Oxford Nanopore we feel hugely privileged to have supported scientists and healthcare professionals in their work to fight the disease.

While researchers in epidemiology, infectious disease, diagnostics, human genetics and immunology directed their efforts towards COVID-19, the determination of broader fields of scientific researchers prevailed, yielding ground-breaking research, in some cases from inventive home lab set-ups during lockdown.

We started the year supporting users in China who were using rapid nanopore sequencing to characterise an emerging new virus, which was soon to be named SARS-CoV-2. The practice of genomic epidemiology, where rapid sequencing of the virus is combined with multiple other data types to inform public health decisions, has now become much better known.  Recognition should be given to scientists who have been driving innovation in this area for many years, and whose response was so fast and so important from the start of this year. While there are many examples, it's important to highlight the ARTIC network, funded by the Wellcome Trust, who released protocols for sequencing SARS-CoV-2 in January so that anyone with access to sequencing technology could rapidly understand how the virus was changing and being transmitted in their country, or even as locally as within their hospital.

The pandemic gave us at Oxford Nanopore a focus to rapidly innovate, and we developed our first regulated in vitro diagnostic test — LamPORE COVID-19 — through the process of invention, development and large scale validation. Through this, we have developed new functions to support the future development of a range of diagnostics that we sincerely believe will have a positive impact in many areas that may include infectious disease, cancer or transplantation.

We'd like to say a huge thank you to all the scientists who continually provide us with feedback on their experiences of using nanopore sequencing. This has enabled us to maintain our approach of continuous improvement, and break through new boundaries this year, in terms of both throughput and accuracy of the technology platform.

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1. Enabling global sequencing of the SARS-C0V-2 virus, to inform COVID-19 public health decisions

The first sequence of the novel coronavirus was made publicly available on 10th January 2020. Soon after, a paper characterising the virus (at the time called nCoV-2019, and subsequently SARS-CoV2 was published in NEJM, citing nanopore sequencing as one of the investigational tools to rapidly understand this emerging respiratory disease.

By this time, the ARTIC network had been working for years to develop end-to-end methods for processing samples from viral outbreaks, to generate real-time epidemiological information that is interpretable and actionable by public health bodies. In January as COVID-19 was gaining momentum, the ARTIC network shared their expertise with the world through the release of a set of materials to assist groups in sequencing SARS-CoV-2 — this included a set of primers, laboratory protocols, bioinformatics tutorials and datasets.

Since the release in January hundreds of thousands of samples have been sequenced using the ARTIC protocol, all over the world.  The necessity of this work has become increasingly apparent over the course of year, especially as sequencing technologies have identified emerging variants.

Visit our community timeline to read about some of the vital work from the Nanopore Community — from whole genome sequencing for genomic epidemiology, to direct RNA sequencing to understand the virus itself, and metagenomic studies to look at the role of co-infections. 

2. Completion of the first human chromosome

The first telomere-to-telomere human chromosome was published in Nature in July this year — a landmark achievement for genomics researchers.

Lead author Karen Miga, from the UC Santa Cruz Genomics Institute, said the project was made possible by new sequencing technologies that enable “ultra-long reads,” such as nanopore technology. The team concluded:

"Our results demonstrate that finishing the entire human genome is now within reach and the data presented here will enable ongoing efforts to complete the remaining human chromosomes."

Read the paper.

3. Our goal is to enable the analysis of anything, by anyone, anywhere

2020 has been the year of the home office or, in the case of the Nanopore Community, the home lab. A global pandemic wasn’t going to stop you from powering up your MinIONs.

Epitomising the accessibility of the MinION, in December student Aspyn Palatnick spoke about an iPhone app for use with the MinION, that he had been developing since the age of 14, with teams from Johns Hopkins University.

4. 200 MinIONs to China

At the end of January, and as COVID-19 was starting to have a significant impact in China, 200 MinIONs left Nanopore HQ in Oxford to support ongoing surveillance of the virus by China’s public health authorities. Lessons learned from teams in China during the early stages of the pandemic were crucial to the surveillance response around the rest of the world in the following weeks and months. Read more.

 

5. Mk1C – the only all-in-one, portable sequencer

2020 has seen the MinION Mk1C become widely available and shipped to labs and field researchers around the world for a truly portable sequencing experience. We’re looking forward to hearing about all the amazing applications of this all-in-one sequencing device as you continue to tell your Mk1C stories.

6. MinION - not sci fi (but can feature in sci fi)

The MinION made it big this year, with not just one Netflix show to its name, but two! If you’re after some holiday viewing, check out documentary Alien Worlds, where the MinION was used to profile extremophiles and drama Biohackers, where the GridION and MinION were used to solve some futuristic mysteries.

7. London Calling moves online - allowing anyone, anywhere to participate

As with many scientific conferences this year, London Calling had a new home for 2020, on the virtual banks of the River Thames. As the online doors opened to a fantastic line up of speakers, we were delighted to have so many people attend from all around the globe. Where the physical venue accommodates 600, we were able to welcome more than 5,000 people through our virtual doors. All the talks are still available to watch in this playlist.

8. Q-Line range to support sequencing in regulated environments

It was at London Calling 2020 that we announced the launch of a new line of products – the Q-Line sequencing portfolio to support users who wish to develop tests based on nanopore sequencing, for deployment in their own environments. Our expectation is that Q line will be useful for applications such as food safety testing or used by labs to develop their own tests.

The ISO9001-qualified Q Line sequencing portfolio from Oxford Nanopore delivers all the benefits of real-time, on-demand sequencing in a locked-down, standardised format — enabling the implementation of routine, long-term workflows for in-house validated assays.

Read more about Q-Line products

9. LamPORE COVID-19: The first in vitro diagnostic from Oxford Nanopore

One morning in mid-April the Oxford Nanopore applications team first discussed the LamPORE method by the end of the day the team had proof of concept that LAMP + nanopore sequencing could detect SARS-CoV-2. Since then, many teams have collaborated to deliver LamPORE. The assay method has been finely tuned, manufacturing processes designed, lab automation procedures developed, validation studies designed and delivered, and regulatory submissions made; all in remarkable time for a new generation of high accuracy diagnostic assay.

We were privileged to support teams at Oxford, Sheffield and Public Health England, Porton Down, who produced the first >500-sample validation study on LamPORE, demonstrating the sensitivity of 99.1% and sensitivity of 99.6%. Subsequently, teams from Birmingham University and collaborators in a number of NHS labs published a remarkable >23,000-sample study showing LamPORE's high-accuracy performance. We're extremely grateful to the teams who conducted these studies and continue to work with multiple partners in the UK and abroad on its deployment.

Find out more about LamPORE and Oxford Nanopore Diagnostics

LamPORE COVID-19 is a molecular diagnostic assay for routine detection of SARS-CoV-2, the virus that causes COVID-19. The assay is highly scalable, allowing deployment in both high-throughput, traditional laboratory settings as well as smaller, local environments — addressing the need for rapid, routine testing of large numbers of people.

LamPORE is CE marked for in vitro diagnostic use and Oxford Nanopore is intending to submit an Emergency Use Authorisation application to the US FDA for LamPORE Covid-19 in the coming weeks.

10. > 98% raw nanopore sequencing accuracy 

Since the first release of our sequencing technology, we have continued to deploy upgrades that drive performance improvements. Whether new data analysis algorithms, new nanopore designs or other new chemistries, these have combined to deliver profound improvements in accuracy and yield over the years.

In 2020 we released a new analysis algorithm — Bonito CRF— which provides increased accuracy single read basecalling, building on previous work to deliver improved performance. It is trained with a larger, more diverse data set and using Bonito CRF we’ve demonstrated 98.3% single read accuracy on currently available sequencing platforms. This >98% performance has also been seen by users. Accurate single reads are just one of a number of ways that nanopore sequencing is providing information-rich, accurate data; for an overview of the tools that are most suitable to achieve high performance sequencing, you can browse this page.

You can read more about Bonito and other detailed updates provided at the Nanopore Community meeting here.

11. Ten terabases of sequence data from a single PromethION

During the spring and summer, we kept our heads down delivering a number of iterative improvements to PromethION flow cells, that we promised in May's London Calling. In November, we started to ship Flow Cells that incorporated these improvements, driving improvements in yields and consistency.

These improvements culminated in our first 10 terabase internal run using all 48 flow cells, a 25% improvement on the previous record. The median output per Flow Cell in this run was 208 Gb — the equivalent of two human genomes over 30X coverage.

This success has been reflected in customer data, with increasing yields reported across a range of applications and further publications in high-throughput areas of sequencing using nanopore. We're excited to go into 2021 able to not only drive ultra-high throughput projects, but provide a more comprehensive package of automation solutions to support these larger project yields.

12. Adaptive sampling: real-world examples of real-time selection of regions of interest

Not one, not  two, but three key pieces of work were published this year demonstrating the role adaptive sampling — real-time electronic selection of molecules of interest — could play in understanding genetic disease.

Payne et al. developed Readfish to enrich targeted panels comprising 25,600 exons from 10,000 human genes and 717 genes implicated in cancer, identifying a single fusion event responsible for a specific type of cancer in less than 15 hours.

Kovaka et al.developed UNCALLED — a novel raw signal mapping algorithm that enables adaptive sampling to enrich sequencing of a collection of 148 human genes associated with hereditary cancers to 30X coverage on a single MinION flow cell.

Finally, Danny Miller concluded that adaptive sampling “could be used as a single data source that replaces most of the (genomic) testing we do today” in his NCM 2020 presentation during which he shared his team’s recent work.

13. We can’t keep up with your publications

It’s hard to believe that labs were shut down for months at a time around the world when you look at the number of publications that have come from the Nanopore Community this year.

Publications featuring nanopore sequencing have doubled since the start of the year, and projects in areas like cancer research are becoming increasingly common where researchers are seeking rapid broader variant information, that includes SVs or methylation. Visit our resource centre to explore the latest.

[Figure shows: data at end of November 2020]

14. Africa Pathogen Genomics Initiative

This year we were delighted to collaborate with Africa CDC and other leading industry partners to launch the new Africa Pathogen Genomics Initiative. The initiative will build a disease surveillance and laboratory network based on genomic sequencing across Africa, including capacity building in 20+ countries. This network will not only help identify and inform research and public health responses to COVID-19 and other epidemic threats, but also tackle endemic diseases such as HIV, tuberculosis, malaria, cholera and other infectious diseases.

Read more about the Africa Pathogen Genomics Initiative

15. The MinION building: 1 year on

In 2019, we opened a new high-tech manufacturing facility near Oxford, that was designed to give us capacity for 4-5 years of rapid growth. The MinION building has been up and running for a year now and 2020 has seen production ramp up significantly, with the ability to produce one flow cell every 30 seconds – that’s 1.2 million flow cells a year. Take a look around:

16. 1% of Icelandic population sequenced with nanopore sequencing, elucidating thousands more variants than before

In a recent paper published by Decode, the team highlight a cohort of 3,622 human genomes —1% of the Icelandic population — which they sequenced using the ultra-high throughput device PromethION. The teams characterised a median of 22,636 Structural Variants per human genome, uncovering variants previously not seen using other technologies.

17. The hottest (sequencing) download in the App store

This year, we released the MinKNOW App for iOS and Android devices. The new MinKNOW App provides a feature-rich user interface with MinKNOW running on Oxford Nanopore sequencing devices, enabling users to monitor experiment progress and control their devices remotely.

The App can also be used to start sequencing runs with the full suite of settings that are available in the desktop app, track previous and running experiments, and manage the device using admin functionality.

Read more and download.

Thanks for your feedback on the MinKNOW app https://twitter.com/ReindertN/status/1331576842931855362

18. Want to see how much information a nanopore long read can really capture?

We wanted to see just how many structural variants you could find in a long read so we took a data set and we turned that into an animation. Watch on to see what we found…

19. The emergence of rapid nanopore HLA typing for tissue transplantation

We often see that clinical researchers are particularly interested in using nanopore sequencing when an insight needs to be fast, accessible, and accurate. This year, we have been supporting more scientists whose goal is to be able to use nanopore sequencing to perform rapid tissue typing for transplantation, especially when time is short because organs are potentially being donated by a deceased donor. We hope that this area will develop further during 2021; you can read some of the publications here.

20. NCM 2020: from single cell transcriptomics to North Sea Ecosurveillance to safe paper

A year in nanopore isn’t complete without the annual Nanopore Community Meeting. Despite being online this year, 2020’s meeting did not disappoint. Talking across three channels — human and translational research, bioinformatics and microbiology and metagenomics — more than 50 speakers took to the virtual stage to share their very latest research.

The themes of the talks reflected trends in your publications – more cancer research, more single cell, more methods that look close to complete assays. All of the talks are available hot off the event platform and ripe for your viewing. We hope you will find them useful and interesting.

We hope that you and your families remained safe during 2020, thank you for your support, and look forward to working together in 2021. 

Dr Gordon Sanghera 

 

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