Judith Breuer from the UCL Institute of Child Health in the UK presented at London Calling 2025 a session titled “How could we incorporate metagenomics into routine diagnostic microbiology?” Breuer defined metagenomics and explained how their work on rapid respiratory metagenomics. In the winter of 2024/2025, the group adapted their clinical metagenomics approaches for rapid 9-12 hour diagnosis using nanopore (Oxford Nanopore Technologies, ONT). The team validated their metagenomics with clinical microbiology cultures/diagnostics and processed 177 samples. Breuer presented data on the performance of the rapid metagenomic approach. Some viruses and were missed, and overall the system had a positive impact on clinical care and was accepted by the clinical staff. Next, Breuer spoke about the GOSH metagenomics trial from tissues and sterile fluids from their hospitals. The method preserves host DNA for biomarker analysis. Nine new pathogens or new causes of encephalitis were identified. All new pathogens were confirmed by extensive testing and sequencing. Breuer presented data from untargeted Illumina, untargeted ONT, and Twist enrichment with Illumina or ONT (LSK). Breuer’s team created a four primer PCR to quickly perform a “four primer” post capture PCR for ONT sequencing. The turnaround time for the Twist capture and PCR for ONT sequencing is just over a day. A second version of the protocol has improved hybridization and decreased turnaround time. Breuer concluded that the rapid metagenomic assay using ONT for respiratory infectious can be customized and is faster than standard microbiology. Breuer also noted that the “targeted nanopore sequencing increases sensitivity of metagenomics to that of targeted short read sequencing enabling use where detection and exclusion of pathogens is critical (“sterile sites”)” I appreciate how the protocols are customizable and now have faster turnaround times than some culture methods!
