Our researchers are developing fast and portable virus sequencing techniques to track viruses in areas with limited medical resources.
Emerging infectious diseases present a significant public health challenge. They can cause sporadic infections, localised outbreaks requiring public health intervention, or, in extreme cases, large epidemics or global pandemics.
RNA viruses are the primary culprits behind emerging infectious diseases. Despite their small genomes and parasitic nature, they have mechanisms that ensure their survival. These viruses, including Ebola, SARS-CoV-2, Zika, and influenza, pose significant risks to public health and the global economy.
Their genomes naturally mutate very rapidly, enabling the processes that drive epidemics. The viral genome enters the host cell via a protective structure called the virion, after which it hijacks the host鈥檚 cellular machinery to replicate, package and propagate itself. Since the viral genome serves as the primary site of all host-virus interactions, understanding it provides valuable insights into viral behaviour and transmission.
Sequencing viral genomes yields critical information: identifying the virus, determining whether it is novel or a re-emergence, tracing its mode of transmission, identifying its origin and understanding what led to its emergence. 鈥淚f you sequence two genomes, you can confidently determine if they are closely related, or if they are a result of separate outbreaks鈥, explained Dr Joshua Quick, a microbiologist at the University 麻豆精选鈥檚 Institute for Microbiology and Infection. Alongside his colleagues, he leads the , a project funded by the Wellcome Trust.
Phylogenetics 鈥 the study of evolutionary relatedness in groups of organisms 鈥 offers additional insights. It helps identify a virus鈥檚 origin, links to previous outbreaks and patterns of transmission. Phylogenetic trees not only map transmission but also highlight specific mutations, such as those enhancing transmissibility or resistance to antiviral treatments. These insights help predict the future trajectory of outbreaks and inform vaccine development.
Scientists construct phylogenetic trees to illustrate viral relatedness and combine them with sampling dates to produce real-time transmission maps or trees. Sequencing and phylogenetic analysis also reveal signs of viral adaptation to hosts, treatments and vaccines.
These insights inform public health authorities about the most effective interventions to control outbreaks.
Genome sequencing technologies have advanced significantly. Unlike traditional sequencing methods which require extensive lab equipment, nanopore sequencing directly reads DNA strands as they pass through a nanopore, enabling portability and real-time analysis.
Quick recalls how technologies have evolved since the West African Ebola Outbreak in 2015, the first time nanopore sequencing was used for real-time epidemic response. 鈥淲e used the from Oxford Nanopore Technologies, which is the first and only nanopore sequencing platform,鈥 said Quick. Before moving to the University 麻豆精选 for his PhD, he worked on making sequencing platforms smaller and more portable. 鈥淪equencing instruments have always been massive, and there has been a trend towards benchtop models,鈥 he said.
This push for miniaturisation led to the release of a USB stick sequencer in 2014 which could read single DNA molecules and perform . Today, real-time sequencing relies on portable instruments referred to as a 鈥榣ab in a suitcase鈥, paired with a laptop for analysis.
While sequencing Ebola genomes, Quick and his colleague, Professor Nick Loman, produced phylogenetic trees by clustering cases and generating real-time outbreak data. 鈥淵ou could investigate a case or a cluster while it was still an active chain of transmission. That鈥檚 the idea behind real-time genomic surveillance,鈥 said Quick. Though niche at the time, real-time genomic surveillance has since become commonplace, improving resolution and accuracy. Since Ebola, it has been used during outbreaks of Zika virus in the Americas, Monkeypox and COVID-19.
Sequencing methods have also evolved. The most basic approach involves extracting and amplifying DNA or RNA and fragmenting the strands into smaller pieces. These fragments are then sequenced and compared to known viral genomes.
Quick and his colleagues developed an improved technique known as , or multiplexed amplicon sequencing. 鈥淚nstead of using conventional methods, we designed a way to amplify the viral genome in small amplicons using PCR鈥攁ll in the same reaction鈥攎aking it highly multiplexed," he said. This technique significantly reduces costs, bringing sequencing expenses to under $10 per sample, allowing for a higher volume of sample analysis.
The method is known as the ARTIC method, and played a critical role in COVID-19 genomic surveillance, accounting for an estimated 18 million out of 20 million genome sequencing experiments during the pandemic. Despite its success, Quick aims to enhance the method further, expanding to detect more diverse viruses. 鈥淎mplicon sequencing works well with outbreaks because all outbreak strains are related, and this makes it easier. We want to use it for more diverse, endemic virus surveillance, such as measles, mumps, rubella and other vaccine-preventable diseases鈥, he said.
The greatest advancements that Quick and his team centre on speed and cost. 鈥淭he scale of sequencing directly correlates with its cost. Amplicon sequencing increases accessibility鈥, he said. In the past, factory-scale sequencing and robotic automation enabled large-scale sequencing at lower costs. However, this approach required researchers to send samples to centralised labs, risking a loss of data control.
The introduction of the MinION, a low-cost, portable sequencer, revolutionised sequencing by increasing the number of labs capable of doing their own genome sequencing. 鈥淭hat鈥檚 the big shift, from centralised to decentralised sequencing, giving researchers the capacity to do it themselves鈥, Quick explained. 鈥淲ith more data generators, the network becomes more resilient, allowing for quicker outbreak detection, broader geographical coverage, and historical sample analysis."
To further democratise genome sequencing, the ARTIC Network have several partners located throughout Africa. 鈥淲e work with the University of Ghana, which served as a central hub during COVID-19. We also have strong partnerships with INRB (Institut National pour la Recherche Biomedicale) in the Democratic Republic of Congo and KEMRI (Kenya Medical Research Institute) in Kenya,鈥 Quick noted.
The network also partners with the Africa Centres for Disease Control (CDC) in Ethiopia and the NICD (The National Institute for Communicable Diseases) in South Africa. These partnerships enhance viral surveillance capabilities and ensure greater global coverage. "Surveillance networks work best when they operate globally, as both people and viruses are highly mobile. Collaborative links strengthen outbreak detection and response," Quick emphasised.
The concept of linked surveillance networks was the founding principle of the ARTIC network. 鈥淭he name ARTIC comes from 'articulated,' reflecting the goal of uniting scientists across borders鈥, Quick explained. However, cross-border collaboration presents challenges. "It involves sharing data across international databases, often requiring researchers to trust that they will receive scientific credit for their contributions. Unfortunately, that trust is not always guaranteed."
To foster transparency and collaboration, Quick and his team make all their research open access. They publish protocols and materials online through multiple platforms, including LinkedIn and protocols.io. "We constantly explore the best ways to provide open-source materials to the scientific community. Our methods have been effective鈥攐ur protocols receive tens of thousands of accesses," he said. Additionally, the ARTIC Network works to eliminate financial and logistical barriers for African research partners by ensuring access to critical lab materials and providing training and technical support.
With funding secured for another five years, Quick and his colleagues plan to continue refining viral genome sequencing methods. Their goal is to develop affordable, accessible sequencing technologies that can function even in resource-limited laboratories. By doing so, they hope to strengthen global surveillance networks, improve outbreak response times, and expand the capacity for real-time epidemic tracking.
Find out more about our Medical Technology and Data research >
UKRI Future Leaders Fellow
Josh is a UKRI Future Leaders Fellow at the University 麻豆精选 developing novel methods for rapid antimicrobial resistance (AMR) prediction at the University 麻豆精选.
Professor of Microbial Genomics and Bioinformatics
Professor Loman works as an Independent Research Fellow in the Institute for Microbiology and Infection at the University 麻豆精选, sponsored by a seven-year MRC Fellowship in Microbial Genomics Bioinformatics.
