Metagenomics for Clinical Infectious Disease Diagnostics Steps Closer to Reality

Abstract

Metagenomics approaches based on shotgun next-generation sequencing hold promise for infectious disease diagnostics. Despite substantial challenges that remain, work done over the past few years justifies excitement about the potential for these approaches to transform how clinical pathogen identification and analysis are performed. In an article in this issue of the , M. I. Ivy et al. (J Clin Microbiol 56:e00402-18, 2018, https://doi.org/10.1128/JCM.00402-18) have applied a shotgun metagenomics approach to the diagnosis of prosthetic joint infections directly from synovial fluid. The results from this work demonstrate both the potentials and challenges of this approach applied in the clinical microbiology laboratory.

Detection and quantification of Erysipelothrix rhusiopathiae in blood from infected chickens – addressing challenges with detection of DNA from infectious agents in host species with nucleated red blood cells

“…Unless host and pathogen cells can be separated in a preliminary stage, the inhibition can only be resolved by diluting the sample, resulting in an obvious loss of sensitivity. Metagenomic sequencing approaches to diagnostics hold great promise for the future beyond PCR [9], but they are even more sensitive to the presence of excessive host DNA.…”

Computational Methods for Strain-Level Microbial Detection in Colony and Metagenome Sequencing Data

“…The ability to quantify and detect bacterial strains within heterogeneous environments has applications in numerous fields including diagnostics (Dekkera, 2018), clinical studies for the microbiome (Wang et al, 2015), bio surveillance (Ahn et al, 2015), tracking transmission of infectious strains in an outbreak (Hong et al, 2014;Ahn et al, 2015;Nayfach et al, 2016), providing insight into the spread of antibiotic resistance (Sukhum et al, 2019), tracking progression of within-host bacterial evolution (Pulido-Tamayo et al, 2015) and exploring diverse environments (Tringe and Rubin, 2005). We look forward to the wide range of applications and effects these tools will have in shaping and progressing sequencing based research.…”

Emerging Options for the Diagnosis of Bacterial Infections and the Characterization of Antimicrobial Resistance

“…Other concerns include ubiquitous contamination from microbial DNA found in reagents, on instruments, and introduced from the environment. Likewise, identification of pathogen signal within what is typically a vast amount of host microbial DNA present in primary specimens represents a serious hurdle for the rapid analysis of sequencing results [ 29 ]. Except for cerebrospinal fluid (CSF) and brain biopsies, all other clinically-relevant biological specimens (e.g., blood, urine) contain host-derived microbes [ 30 ], which also undergo sequencing by mNGS.…”