mNGS in clinical microbiology laboratories: on the road to maturity

Abstract

Metagenomic next-generation sequencing (mNGS) is increasingly being applied in clinical laboratories for unbiased culture-independent diagnosis. Whether it can be a next routine pathogen identification tool has become a topic of concern. We review the current implementation of this new technology for infectious disease diagnostics and discuss the feasibility of transforming mNGS into a routine diagnostic test. Since 2008, numerous studies from over 20 countries have revealed the practicality of mNGS in the work-up of undiagnosed infectious diseases. mNGS performs well in identifying rare, novel, difficult-to-detect and coinfected pathogens directly from clinical samples and presents great potential in resistance prediction by sequencing the antibiotic resistance genes, providing new diagnostic evidence that can be used to guide treatment options and improve antibiotic stewardship. Many physicians recognized mNGS as a last resort method to address clinical infection problems. Although several hurdles, such as workflow validation, quality control, method standardisation, and data interpretation, remain before mNGS can be implemented routinely in clinical laboratories, they are temporary and can be overcome by rapidly evolving technologies. With more validated workflows, lower cost and turnaround time, and simplified interpretation criteria, mNGS will be widely accepted in clinical practice. Overall, mNGS is transforming the landscape of clinical microbiology laboratories, and to ensure that it is properly utilised in clinical diagnosis, both physicians and microbiologists should have a thorough understanding of the power and limitations of this method.

Keywords:

• Metagenomics
• mNGS
• next-generation sequencing
• real-time sequencing
• microbiology

Acknowledgements

The authors thank Dr. Yongjun Li and Dr. Xuejing Gou from Vision Medicals, Guangzhou, China and Dr. Hao Wu from BGI Clinical Laboratory Co., Ltd, Wuhan, China for giving us advice and comments in the preparation of the manuscript.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

JL conceived the idea: DH, ZL and RZ drew the figures: DH, RL and PT collected the literature and DH wrote the paper. All authors have read and approved the final version of the manuscript.

Additional information

Funding

This work was supported by the “AIDS and Hepatitis, and Other Major Infectious Disease Control and Prevention” Programme of China under Grant [No. 2018ZX10102001] and by the National Natural Science Foundation of China under Grant [No. 81703276].