Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids
- 9 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 27 (1), 115-124
- https://doi.org/10.1038/s41591-020-1105-z
Abstract
We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S–internal transcribed ribosomal gene spacer (28S–ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12 patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids.Keywords
Funding Information
- Abbott Laboratories
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (R01-HL105704)
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R33-AI120977)
- U.S. Department of Health & Human Services | National Institutes of Health (K08-CA230156-01)
- Burroughs Wellcome Fund
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