InfeCtion respONse through vIrus genomiCs (ICONIC)

a) Unmet Need Viruses are a major cause of morbidity and mortality, with a high cost to the NHS. Viruses have significant genomic variation, which underpins pathogenicity, drug resistance, and transmission. To date, viral gene sequencing has only been considered for detection of specific drug resistance determinants for HIV in particular. However, despite enormous advances in technology, we currently lack the systems, facilities and capacity to routinely capture full-length viral gene sequences, to monitor drug resistance at the granularity to optimally guide treatment, to identify the source of viral transmissions within healthcare settings, and to track emerging epidemics. b) Technology for development We have developed viral full-length gene sequencing and will deploy this in a sustainable and robust format. We will utilise Sureselect technology to capture virus genomes from clinical samples, for next generation sequencing. To process and assemble virus genomes from NGS data without the need for embedding complex computer technology in the NHS we will take advantage of cloud based' computation with anonymisation of each sample. We will develop around our Amazon Web Service (AWS) method Silverline' for the de novo assembly of virus genomes. c) Key Goals and Deliverables We will use exemplars that illustrate the benefit to direct/stratified patient management (HIV, HCV), infection control (norovirus), and national surveillance (measles, influenza), and assess the capacity for embedding this new technology within the UK diagnostic environment, in a sustainable and cost effective manner. Our explicit deliverables are to i) deploy optimal methods for preparing clinical and surveillance isolates for sequencing, ii) demonstrate robust and reliable real time full length sequencing, iii) deliver data to users in an a form suited to inform direct clinical care, hospital control, and intervention in epidemics, iv) use decision support, implementation research, health economics and assessment of commercialisation potential, in order to develop a sustainable model for use. d) Healthcare Impact Our technology will lead to (i) more effective treatment of HIV and HCV infections, (ii) more targeted hospital infection control regarding norovirus infections, and (iii) better dynamic assessment and targeted management of community based viral outbreaks, in particular measles and influenza (b) For lay