Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection

Annu Rev Pathol. 2019 Jan 24:14:319-338. doi: 10.1146/annurev-pathmechdis-012418-012751. Epub 2018 Oct 24.


Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. The review covers ( a) next-generation sequencing technologies and common platforms, ( b) next-generation sequencing assay workflows in the clinical microbiology laboratory, ( c) bioinformatics analysis of metagenomic next-generation sequencing data, ( d) validation and use of metagenomic next-generation sequencing for diagnosing infectious diseases, and ( e) significant case reports and studies in this area. Next-generation sequencing is a new technology that has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases.

Keywords: clinical diagnostics; infectious disease; metagenomics; nanopore sequencing; next-generation sequencing; pathogen detection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Communicable Diseases / diagnosis*
  • Communicable Diseases / microbiology
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Metagenome
  • Metagenomics / methods*
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, RNA / methods