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      Clinical metagenomics

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          Abstract

          Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.

          Abstract

          Clinical metagenomic next-generation sequencing (mNGS) is rapidly moving from bench to bedside. This Review discusses the clinical applications of mNGS, including infectious disease diagnostics, microbiome analyses, host response analyses and oncology applications. Moreover, the authors review the challenges that need to be overcome for mNGS to be successfully implemented in the clinical laboratory and propose solutions to maximize the benefits of clinical mNGS for patients.

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          Most cited references87

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          In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.
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            Gene-expression signatures in breast cancer.

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              Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing.

              The Gram-negative bacteria Klebsiella pneumoniae is a major cause of nosocomial infections, primarily among immunocompromised patients. The emergence of strains resistant to carbapenems has left few treatment options, making infection containment critical. In 2011, the U.S. National Institutes of Health Clinical Center experienced an outbreak of carbapenem-resistant K. pneumoniae that affected 18 patients, 11 of whom died. Whole-genome sequencing was performed on K. pneumoniae isolates to gain insight into why the outbreak progressed despite early implementation of infection control procedures. Integrated genomic and epidemiological analysis traced the outbreak to three independent transmissions from a single patient who was discharged 3 weeks before the next case became clinically apparent. Additional genomic comparisons provided evidence for unexpected transmission routes, with subsequent mining of epidemiological data pointing to possible explanations for these transmissions. Our analysis demonstrates that integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission.
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                Author and article information

                Contributors
                charles.chiu@ucsf.edu
                Journal
                Nat Rev Genet
                Nat. Rev. Genet
                Nature Reviews. Genetics
                Nature Publishing Group UK (London )
                1471-0056
                1471-0064
                27 March 2019
                2019
                : 20
                : 6
                : 341-355
                Affiliations
                [1 ]ISNI 0000 0001 2297 6811, GRID grid.266102.1, Department of Laboratory Medicine, , University of California, ; San Francisco, CA USA
                [2 ]ISNI 0000 0001 2297 6811, GRID grid.266102.1, Department of Medicine, Division of Infectious Diseases, , University of California, ; San Francisco, CA USA
                Author information
                http://orcid.org/0000-0003-2915-2094
                Article
                113
                10.1038/s41576-019-0113-7
                6858796
                30918369
                27ec3872-a4be-4fb0-899b-014a94095f2d
                © Springer Nature Limited 2019

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Categories
                Review Article
                Custom metadata
                © Springer Nature Limited 2019

                infectious diseases,microbial genetics,next-generation sequencing,metagenomics

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