Metagenomic Sequencing for Agnostic Viral Pathogen Detection: Promise and Barriers to Clinical Adoption
This review evaluates the state of metagenomic next-generation sequencing (mNGS) as a hypothesis-free diagnostic tool for viral pathogens. Unlike targeted multiplex PCR or amplicon-based NGS, metagenomics sequences all nucleic acids in a sample without requiring prior knowledge of the pathogen genome. The authors highlight recent performance improvements and clinical applications while detailing the technical, regulatory, and bioinformatic challenges that have prevented widespread deployment in clinical microbiology laboratories.
The original study
Agnostic Sequencing for Detection of Viral Pathogens.
- Authors
- Gauthier NPG, Chorlton SD, Krajden M, Manges AR
- Journal
- Clinical microbiology reviews
- Type
- Journal Article, Review, Research Support, U.S. Gov't, Non-P.H.S.
- PMID
- 36847515
Original abstract
The advent of next-generation sequencing (NGS) technologies has expanded our ability to detect and analyze microbial genomes and has yielded novel molecular approaches for infectious disease diagnostics. While several targeted multiplex PCR and NGS-based assays have been widely used in public health settings in recent years, these targeted approaches are limited in that they still rely on a priori knowledge of a pathogen's genome, and an untargeted or unknown pathogen will not be detected. Recent public health crises have emphasized the need to prepare for a wide and rapid deployment of an agnostic diagnostic assay at the start of an outbreak to ensure an effective response to emerging viral pathogens. Metagenomic techniques can nonspecifically sequence all detectable nucleic acids in a sample and therefore do not rely on prior knowledge of a pathogen's genome. While this technology has been reviewed for bacterial diagnostics and adopted in research settings for the detection and characterization of viruses, viral metagenomics has yet to be widely deployed as a diagnostic tool in clinical laboratories. In this review, we highlight recent improvements to the performance of metagenomic viral sequencing, the current applications of metagenomic sequencing in clinical laboratories, as well as the challenges that impede the widespread adoption of this technology.