33rd International Dynamics & Evolution of Human Viruses

DAMPA - accelerated and simplified design of probe panels for targeted metagenomics using pangenome graphs.

May 20, 2026, 11:30 AM

20m

Oral Software, tools & methods Software, Tools & Methods

Speaker

Dr Michael Payne (Sydney Infectious Diseases Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia)

Description

Direct-from-sample sequencing is an essential tool in modern clinical and public health microbiology, particularly for sequencing viruses or unculturable pathogens, and for diagnostic metagenomics. Targeted metagenomics uses sets of oligonucleotide probes (up to 100,000s) to selectively sequence targeted loci or genomes from hundreds of pathogen species simultaneously, removing the need to identify or isolate the pathogen first. Targeted metagenomics is undergoing a rapid uptake globally, especially for applications such as syndromic surveillance for respiratory or vector-borne infections. However, uptake is currently limited by a lack of efficient tools for assay design.

In this work we present DAMPA (Diversity Aware Metagenomic Panel Assignment), a user-friendly probeset design pipeline that uses evolutionary relationships between targeted loci, represented as a pangenome graph, to design an optimal probeset. Conserved regions require only a few graph nodes, while rapidly evolving regions are represented by complex graph structures with more nodes. In this way, DAMPA ensures that the diversity of all regions is represented in the final probe set while minimising probe redundancy, and maintains probe performance as evolutionary distance increases.

We evaluated the performance of DAMPA on a range of datasets including viruses with diverse genome structure and size, including Dengue, HIV, Enterovirus, Epstein Barr virus (EBV), Japanese Encephalitis Virus (JEV) and a bacterium (Bordetella pertussis). DAMPA generated probe sets with complete coverage for all targeted organisms. DAMPA ran on datasets containing large genomes (B. pertussis, 4Mb) or large sample numbers (Dengue, 16,000) and was 6x faster than existing tools, generating probesets in under 30 seconds on a standard laptop.

Experimental validation in clinical samples positive for Enterovirus, which is notoriously prone to coverage dropouts due to high genotype diversity, showed that DAMPA-designed probes were highly sensitive, quantitative and generated more even read coverage across genomes than the commercially available Twist Comprehensive Viral Research panel.