Squiggles to the rescue: metagenomics-based pathogen surveillance | LC26

Abstract
Genomics has become an integral part of One Health surveillance for identifying pathogen and resistance outbreaks. Nanopore sequencing holds the promise of implementing rapid genomic sequencing at the point of care and potentially globally due to the low upfront investment costs. I will show our contributions to benchmarking whole-genome sequencing of foodborne and clinical pathogens by nanopore sequencing in comparison with established diagnostics and traditional short-read sequencing technologies. I will then describe our research on metagenomic surveillance by nanopore sequencing, which — unlike culture-based whole-genome sequencing — can be applied rapidly to any sample type and has the potential to holistically and agnostically assess the presence of all pathogens, their genomic variation, and antimicrobial resistance. I will specifically describe how we use deadly foodborne and clinical pathogens (Listeria and carbapenem-resistant Enterobacterales species) to compare the results of rapid metagenomics with established diagnostics. We explore how nanopore data and AI can address challenges associated with metagenomics in terms of sensitivity, viability, and associations of resistance genes to their pathogenic hosts. Using mock metagenomic datasets, we establish the sensitivity of Adaptive Sampling enhanced nanopore metagenomics, which can recover a variety of pathogen subtypes while whole-genomic characterizations are inherently limited to the detection of one pathogenic strain. We further show that epigenetic information can give insights into plasmid-host associations and the metabolic state of the pathogen — including the viable-but-not-culturable state that is known to lead to high false-negative rates in established approaches. Using real-world datasets, we finally show the promise and limitations of our nanopore- and AI-based approaches.

Biography
Lara Urban is a statistical geneticist and ecologist with a PhD in computational genomics from the University of Cambridge and the European Bioinformatics Institute (EMBL-EBI) and has independent research experience with the national Department of Conservation as a Humboldt Fellow in New Zealand. Since 2022 Lara has led her own research group, now as a professor at the University of Zurich and its Food Safety and One Health Institutes, and previously as Helmholtz Principal Investigator at the Helmholtz AI Institute with a faculty position at the Technical University of Munich. Lara was named the Young Scientist of the Year by the German Association of University Professors in 2023.