Our vision of the future is to harness faster, more convenient, and widely available technology, to bring a host of benefits to diverse communities. From operating theatres to pharmacies, farms to food production supply chains, classrooms to homes, we aim to enable the analysis of anything, by anyone, anywhere.

How portable sequencing is tackling loss of biodiversity

Loss of biodiversity is one of the most urgent crises facing our planet — more than 40,000 species are threatened with extinction today1. Sequencing is a critical tool for understanding the biology, development, and environmental interaction of endangered species.

Genomic insights can help with existing conservation work by providing information on species identity, genetic disease risk, and how an organism has evolved. Identifying the DNA sequence of critically endangered species holds immeasurable value in preventing further species loss.

Nanopore sequencing technology is helping researchers around the world to support conservation in remote locations through the ORG.one programme — which was established in 2021 to support the sequencing of critically endangered species, through the provision of free-of-charge consumables.

Conservation biology relies on ongoing monitoring and is therefore dependent on community support and local participation. Due to the accessibility and portable nature of nanopore sequencing technology, it can be used to carry out rapid sequencing of critically endangered species close to their origin and with the involvement of local communities. Since the ORG.one programme began, more than 50 critically endangered species have been sequenced, including the Brown-headed spider monkey in Ecuador and the European sturgeon in the Netherlands.

Ultimately, the aim of the programme is to develop an active and distributed community of conservationists, scientists, and bioinformaticians to support the generation and communication of open data for conservation genomics.

Improving organ transplant success rates

Organ transplantation has been a huge success over the last 50 years; however, most transplants are typically short lived. The average survival rate post kidney transplant, for example, is only about 12 years2 and many fail within the first few years due to rejection, predominantly antibody-mediated rejection, which results from patient antibodies binding to antigens on the donor tissue.

Karen Sherwood and Paul Keown from the University of British Colombia, Canada, are part of a team working to both better characterise organs for transplantation and monitor the immune response in individuals after transplantation, with the aim of increasing organ donation success rates. The team developed a simple workflow that utilises the MinION device to rapidly sequence the antigens on the donor tissue to check for compatibility prior to transplantation — something that has not existed as a single solution to date.

The protocol the team developed is applicable to time-sensitive applications, such as deceased donor typing, enabling better assessments of compatibility. The technology enables significantly shorter turnaround time for multiple samples, and at a lower cost than existing solutions.

Karen commented that nanopore sequencing offers ‘tremendous potential for speed, depth, and flexibility in both discovery and delivery sciences, and is approaching the point of clinical application’.

This team is just one of many applying nanopore sequencing to tissue typing. Last year, in recognition of a shift to nanopore sequencing in this space, global transplantation diagnostic company, Omixon, released NanoTYPE — a kit to specifically support tissue typing using nanopore sequencing.

A new frontier in disease characterisation

There are around 7,000 known rare genetic conditions affecting about 400 million people around the world. While three-quarters of rare diseases affect children, close to one-third of the children do not live to see their fifth birthday3.

Current methods of clinical testing for rare genetic conditions can take months or years to complete, and after this full workup, around 50% of children remain undiagnosed4. Danny Miller from the University of Washington, USA, is working to identify genetic conditions more effectively, while reducing the time it takes to make a genetic diagnosis.

He has been using nanopore technology to identify disease causing variants in clinical research samples not identified by standard testing and believes it has the potential to end the ‘diagnostic odyssey’ that many families with rare genetic disorders have found themselves on. Using a flexible, computational targeted sequencing approach, he was able to look at specific regions of the genome in real-time for analysis — a method only possible using nanopore technology.

Using this targeted-sequencing approach, his team clarified complex structural genomic changes and identified missing genomic variants. In addition, they could generate these results quickly — in one case, in just three hours from birth.

Danny argues that this approach offers the potential to be used as a single sequencing test to replace nearly all other clinical genetic tests offered today. This would in turn reduce cost, reduce wait times, increase treatment options, and allow patients and families to make more informed healthcare decisions.

A truly complete human genome

The Human Genome Project was launched in 1990 and yet more than 30 years later the full sequence of the human genome was still incomplete. Until 2021, it wasn’t possible to see around 8% of the human genome.

This missing information was not overlooked due to its lack of importance, but rather due to technological limitations. Addressing this, Karen Miga from the University of California, Santa Cruz and the Telomere-to-Telomere (T2T) Consortium finished the first truly complete 3.055 billion base pair sequence of a human genome, representing the largest improvement to the human reference genome since its initial release in 2003.

Oxford Nanopore ‘ultra-long reads’, where the technology can uniquely sequence megabase-long fragments of DNA in one continuous analysis, were vital in being able to bring the assembly together — spanning some of the most complex regions of the human genome, which until that time had been unresolved.

This complete human genome will enable researchers to see the full picture and therefore gain more insights about health and disease. The authors concluded that ‘The complete, telomere-to-telomere assembly of a human genome marks a new era of genomics where no region of the genome is beyond reach.’

Sequencing to fundamentally change critical care

It took teams of scientists around the globe 13 years and three billion dollars to sequence the first human genome. In 2021, a team led by scientists at Stanford University, USA, used Oxford Nanopore’s PromethION 48 device to break the record for the fastest whole human genome ever sequenced — it took just five hours and two minutes.

Such rapid, whole-genome sequencing has the potential to enable the identification of rare genetic disorders in critically ill patients faster than ever before. Traditionally, characterisation of variants that cause genetic disease using whole-genome sequencing has taken days or weeks to return a result. In time-critical contexts, this approach has therefore not been viable to date.

In a study, the team at Stanford sequenced 12 unique research samples from patients aged between three months to 57 years using their rapid workflow and identified disease-causing variants in as little as seven hours and 18 minutes. A disease-causing or likely disease-causing mutation was identified in five of the 12 samples analysed.

According to the team, this ‘informed clinical management (including sympathectomy, heart transplantation, screening, and changes in medication) for each of the five patients or their family members’.