COG-UK recently launched a scheme to fund new research, with a particular focus on metagenomics. We are pleased to announce that four awards have been made to teams led by Professor Emma Thomson (MRC-University of Glasgow Centre for Virus Research), Dr Thushan de Silva (The University of Sheffield), Professor Oliver Pybus (Royal Veterinary College and University of Oxford), and Dr Patrick McClure (University of Nottingham). Each of the four projects will develop and apply cutting edge metagenomic approaches to look for viruses with the potential to impact on human health. Find more details about their projects below.
Congratulations to the recipients of these awards.
Professor Emma Thomson and co-applicants Dr Ana Filipe and Professor David Robertson (MRC-University of Glasgow Centre for Virus Research) are funded for the project “Identification of viruses causing undiagnosed febrile illness in returning travellers to the UK using enhanced NGS-based metagenomic methods”. Imported viruses pose a substantial threat to the health and wellbeing of the UK population. The SARS-CoV-2 virus was introduced to the UK more than 1000 times in the first month of the epidemic, and the recent detection and transmission of monkeypox virus in the UK highlights the risk of imported infection becoming established in the population. Furthermore, cases of Ebola, Lassa fever, Seoul hantavirus and Crimean-Congo haemorrhagic fever viruses have all been imported to the UK in the last 10 years (the majority initially misdiagnosed), highlighting the risks of imported infection and a diagnostic gap that could be filled using novel agnostic testing technologies. In partnership with the Rare and Imported Pathogens Laboratory (from UK Health Security Agency), using undiagnosed samples from returning travellers to the UK, the research team will evaluate the capacity for emerging metagenomic methods to enhance the diagnosis of viruses causing disease in this important risk group.
Dr Thushan de Silva (The University of Sheffield) is funded for the project “Optimising pan-viral metagenomics by sequence hybridisation in respiratory and stool specimens from immunosuppressed and critically ill patients”. While untargeted metagenomic sequencing of clinical samples can provide valuable viral genomic data in specific cases, the relatively low abundance of viral nucleic acid compared to human and bacterial DNA/RNA means the sequencing process is inefficient. This can result in an insensitive assay, poor genome coverage, or in the need to run samples at very low throughput to recover enough viral reads which can be costly. This is a problem when considering metagenomic sequencing for surveillance, especially in low- and middle-income countries, or in clinical settings where a higher throughput of samples would be desirable. Thushan and colleagues will establish a new method to enhance efficient recovery of viral genomes using Oxford Nanopore Technology sequencing devices, and will characterise the virome in immunosuppressed and critically ill patients. This will build on existing collaborations with investigators at the MRC-University of Glasgow Centre for Virus Research to establish optimum methods for enriching viral reads from respiratory and stool samples, including the best approaches for recovering both RNA and DNA viruses and enhancing sample throughput.
Professor Oliver Pybus (Royal Veterinary College and University of Oxford) and co-applicants Dr Jayna Raghwani (University of Oxford), Dr Sarah Hill (Royal Veterinary College) and Dr Sarah François (University of Oxford) are funded for the project “Harnessing real-time, portable metagenomics for discovering and monitoring of emerging viruses”. Rapid identification of causative viruses during emerging outbreaks is critical for effective public health responses and patient care. Metagenomic sequencing can identify a causative pathogen while also generating virus genome data for phylogenetic investigation of disease origin, evolution and transmission. Metaviromic sequencing is typically conducted using high-cost sequencing infrastructures that are frequently only available in well-resourced countries or centralised government laboratories, but outbreaks caused by zoonotic spillover are more likely to occur in remote or rural locations of low- and middle-income countries that typically lack such sequencing capacity. The research team will test and optimise approaches for virus metagenomics on portable sequencing platforms, improving enrichment of viral reads using on-device selective sequencing. This will contribute to efforts to detect zoonotic viruses and use virus genomes to reconstruct unobserved outbreak dynamics, even in resource-limited settings. This project will also advance approaches for faster and more sensitive detection of emerging viral outbreaks globally.
Dr Patrick McClure (University of Nottingham, (UoN)) and co-applicants Dr Michelle Lister (Nottingham University Hospitals Trust, (NUHT)), Professor Matt Loose (UoN), Dr Gemma Clark (NUHT), Dr Louise Berry (NUHT / Honorary UoN), Dr Hannah Howson-Wells (NUHT), Dr Vicki Fleming (NUHT), Dr Nik Mahida (NUHT), Professor Jonathan Ball (UoN), Dr Theocharis Tsoleridis (UoN) are funded for the project “Exploring the undiagnosed infectious burden of inpatient respiratory disease by metagenomics”. While the SARS-CoV-2 pandemic has emphasised respiratory pathogens as an acute threat to global public health, ongoing outbreaks such as monkeypox and acute hepatitis of unknown origin in children reinforce the need for disseminated, rapid and flexible molecular diagnostic tools beyond those that are available to most NHS laboratories. To address this shortfall, the research team will further develop their in-house partnership and capability for diagnostic metagenomics using both targeted and unbiased methodologies. They will focus on samples from patients that have been hospitalised with symptomatic undiagnosed respiratory illness, including critically ill cohorts requiring intensive high dependency care.
