The evolution of pathogen genome sequencing: targeted to agnostic strategies | ESCMID Global 2026

Abstract: The evolution from targeted sequencing to metagenomics represents a transformative journey in pathogen detection and surveillance. In NHS Lothian (Edinburgh, UK), our work initially focused on implementing published protocols for national programs, including SARS-CoV-2 and poliovirus surveillance, ensuring rapid and reliable genomic insights during critical public health responses.

This capability was further demonstrated during the mpox outbreak, where rapid deployment of sequencing workflows enabled timely outbreak characterization. Building on these experiences, we transitioned to developing in-house methods, such as whole-genome sequencing for respiratory syncytial virus (RSV), expanding our capacity beyond established protocols. Our applications have also extended to bacterial pathogens, exemplified by sequencing ceftriaxone-resistant Neisseria gonorrhoeae, supporting antimicrobial resistance monitoring.

Moving toward broader approaches, we are introducing 16S rRNA sequencing for routine service, enabling comprehensive bacterial profiling. Ultimately, these developments converge on respiratory metagenomics — an agnostic, high-resolution approach currently in validation — which promises to revolutionize diagnostics by detecting diverse pathogens in a single assay. This progression highlights the adaptability and innovation required to meet evolving clinical and public health challenges through genomics.