Development of novel rapid diagnostics for sepsis using the latest nanopore sequencing technologies

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Rapid diagnosis is critical for the effective clinical management of life-threatening infections, especially bloodstream infections (BSI). This is because every hour delay in effective antimicrobial therapy increases risk of mortality by 10%. The gold standard for the diagnosis of BSI is blood culture. However, culture has low sensitivity and a long turnaround time, with results only available 2-5 days after sample collection. Slow diagnostics lead to: 1) poor patient outcomes, 2) the overuse of broad-spectrum antibiotics, which promotes the emergence of antimicrobial resistance (AMR) and 3) increased hospital costs. Nanopore sequencing based clinical metagenomics could replace culture, as it is rapid and can detect any pathogen and AMR gene in a sample.The PhD project aims:1. to develop a metagenomics sequencing-based BSI diagnostic pipeline combining novel pathogen enrichment and host depletion technologies with nanopore sequencing and analysis2. to optimise, evaluate and validate the method on spiked blood samples3. to clinically evaluate the pipeline on blood samples from patients with suspected sepsis/BSI.4. to develop and apply bioinformatic analysis tools that utilise the diagnostic metagenomic data for public health applications, such as hospital infection control and pathogen molecular epidemiology