Metagenomics for pathogen detection in public health

Abstract

Traditional pathogen detection methods in public health infectious disease surveillance rely upon the identification of agents that are already known to be associated with a particular clinical syndrome. The emerging field of metagenomics has the potential to revolutionize pathogen detection in public health laboratories by allowing the simultaneous detection of all microorganisms in a clinical sample, without a priori knowledge of their identities, through the use of next-generation DNA sequencing. A single metagenomics analysis has the potential to detect rare and novel pathogens, and to uncover the role of dysbiotic microbiomes in infectious and chronic human disease. Making use of advances in sequencing platforms and bioinformatics tools, recent studies have shown that metagenomics can even determine the whole-genome sequences of pathogens, allowing inferences about antibiotic resistance, virulence, evolution and transmission to be made. We are entering an era in which more novel infectious diseases will be identified through metagenomics-based methods than through traditional laboratory methods. The impetus is now on public health laboratories to integrate metagenomics techniques into their diagnostic arsenals.

Figure 1

Workflow outlining a pipeline of laboratory and bioinformatics methods required for metagenomic pathogen detection. The left side (pale blue) lists each step in the metagenomics workflow and the right side lists the tools used for each stage. Boxes on the right are color-coded to indicate the type of tool used: dark blue, laboratory method; gray, data format; green, computer software; maroon, database. BWA, Burrows-Wheeler Aligner; BLAST, Basic Local Alignment Search Tool; IMG, integrated microbial genomics; MG-RAST, Metagenomics Rapid Annotation Server.

Figure 2

Strategy for novel pathogen detection in public health. Currently, specimens are sent for conventional laboratory tests. If one of these tests is positive (dashed arrows), then an actionable result is generated. If these are all negative, then investigational methods such as metagenomics can be employed afterwards (white arrows). With advances in metagenomics, these methods may be performed earlier in the diagnostic algorithm in the future (black arrows) instead of following multiple traditional laboratory tests.