Increasing the capacity and capability, and accessibility to the local population, of health-related omics research in Hull

The PromethION24 is a device used to analyse the nature of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in detail in clinical samples, and in bacteria, viruses or fungi identified from samples. The information generated by a PromethION24 can inform doctors and researchers about unique 'signals' within clinical samples, or the DNA/RNA of bacteria, viruses, or fungi, identified from such samples, which can help understanding of the processes that cause disease and develop new diagnostic tests, and/or inform about how an infection spreads within a population. This in turn can inform about how to control and/or improve the treatment of a condition. This so-called "genomics" technology (sometimes called "omics" which is a broader term for related research) has been used extensively in the COVID-19 pandemic.

Hull University Teaching Hospitals (HUTH) has a rapidly expanding range of research, in areas of work the MRC is interested in funding. In collaboration with the University of Hull and Hull York Medical School, doctors at HUTH are applying "omics" to a range of clinical samples, which has resulted in local expertise using a related, but much lower throughput device called MinION. Capacity and capability to grow further is currently severely limited by this lower throughput technology. The PromethION24 will be housed in a laboratory based in the Daisy Building on the Castle Hill Hospital campus of HUTH. All co-applicants are based here, with Hull Royal Infirmary and the University of Hull close by, allowing easy transport of samples and close collaboration between clinical doctors and researchers. The PromethION24 delivers 24-times to 120-times more throughput, retains a low laboratory 'footprint', and overall reduces the cost of analysing each sample.

High quality laboratory space in the Daisy Building at HUTH is dedicated to the careful storage and processing of patient samples for this type of research. Such analyses require powerful computers to analyse, interpret and store the produced data and this will be supported by the University of Hull VIPER supercomputer, which is one of the most powerful in the north of England, and supports current research. The Dept. of Research & Development, HUTH will oversee use and governance via a new "omics" committee, that will allow new research questions of notable local and national importance to be addressed with a focus initially on infection and wound related projects. Early projects will include studies of: the nature of bacteria in wounds and how they influence healing; the fungi on the skin and in the mouth of patients with acute leukaemia before, during and after they receive intensive chemotherapy and how this links to antifungal drug use and whether they develop an infection (linked to a NIHR funded trial, BioDriveAFS); bacteria that cause bloodstream infections in people who inject drugs compared to those who do not, and how this links to their infection and the spread of these bacteria in the community; the relationship between the nature of antibiotic resistant bacteria and how well a two antibiotic based therapy works against them in the laboratory; and the bacteria and unique 'signals' identified in the large joint fluid (e.g. knee) of patients with and without bacterial (septic) arthritis.

Access will be available to other HUTH clinicians, and partner organisations, in keeping with our intended collaborative use, leading to data to support a programme of related future external funding applications, and a step-change in "omics" research locally. Importantly, the technology will increase research participation opportunities for local patients, who live in an area with high disease burden and that has been underserved by research activity. The award will also provide a platform for expanding "omics" education of local healthcare professionals and researchers, as well as facilitating increasing contributions to national genomics research projects.

The PromethION24 uses nanopore DNA/RNA sequencing technology to sequence DNA/RNA in real-time and supports metagenomics, whole genome sequencing (WGS) and transcriptomics. Hull University Teaching Hospitals (HUTH) has a rapidly expanding portfolio of MRC-remit research exploiting such technology for patient benefit. In collaboration with the University of Hull and Hull York Medical School, clinicians at HUTH are applying "omics" to a range of clinical samples, which has resulted in extensive local expertise with an established MinION based bioinformatics pipeline at HUTH. Capacity/capability to grow further is severely limited by the low throughput MinION.

The PromethION24 will be housed at HUTH, where all co-applicants are based, delivering 24- to 120-times more throughput while maintaining a low laboratory 'footprint', and reducing per sample costs. High quality laboratory space at HUTH is dedicated to the storage/processing of samples with downstream analyses supported by the University of Hull VIPER supercomputer. The Dept. of Research & Development, HUTH will oversee use and governance of the technology via committee, that will allow new research questions of notable local/national importance to be addressed with a primary focus on applying long read community microbiome profiling and WGS to infection and wound-related projects (see Case for Support). Access will be available to other HUTH clinicians, and researchers at partner organisations, in keeping with our intended collaborative use, leading to data to support a cadre of future external funding applications, and a step-change in "omics" research locally. Importantly, the technology will increase research participation opportunities for local patients, who live in an area with high disease burden. The award will also provide a platform for expanding "omics" education of local healthcare professionals and researchers, as well as facilitating increasing contributions to national genomics consortia.