Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections

Abstract

Metagenomic next-generation sequencing (mNGS) has changed the diagnosis landscape of lower respiratory tract infections (LRIs). With the development of newer sequencing assays, it is now possible to assess all microorganisms in a sample using a single mNGS analysis. The applications of mNGS for LRIs span a wide range of areas including LRI diagnosis, airway microbiome analyses, human host response analyses, and prediction of drug resistance. mNGS is currently in an exciting transitional period; however, before implementation in a clinical setting, there are several barriers to overcome, such as the depletion of human nucleic acid, discrimination between colonization and infection, high costs, and so on. Aim of Review: In this review, we summarize the potential applications and challenges of mNGS in the diagnosis of LRIs to promote the integration of mNGS into the management of patients with respiratory tract infections in a clinical setting. Key Scientific Concepts of Review: Once its analytical validation, clinical validation and clinical utility been demonstrated, mNGS will become an important tool in the field of infectious disease diagnosis.

Keywords: ARGs, antibiotic resistance genes; CAP, Community-acquired pneumonia; CSF, Cerebrospinal fluid; DASH, Depletion of Abundant Sequences by Hybridization; DNBs, DNA nanoballs; DNase, Deoxyribonuclease; Fil, 5-μM filtration; IQC, Internal quality control; IQR, Interquartile range; LDTs, Laboratory-developed tests; LRIs, Lower respiratory tract infections; MTB, M. tuberculosis; Metagenomics; Mol, MolYsis™ Basic; NCBI, National Center for Biotechnology Information; NEB, NEBNext® Microbiome DNA Enrichment Kit; NPA, nasopharyngeal aspirate; Next generation sequencing; PMA, Propidium monoazide; PT, Proficiency testing; Pneumonia; QIA, QIAamp DNA Microbiome Kit; RMB, renminbi; RT-PCR, Reverse-transcription PCR; RVP, respiratory virus panel; Respiratory; RoC, Receiver-operating curve; SMRT, single-molecule real-time sequencing; TATs, Typical turnaround times; WGS, Whole-genome sequencing; mNGS; mNGS, Metagenomic next-generation sequencing.