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Metagenomics using next-generation sequencing can identify a wide range of pathogens, including rare or novel microorganisms.
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New mNGS Tool Elevates Microbial Identification Workflows

Latest study explores global genetic characterization of samples using metagenomics and NGS in diagnosing infections

Institut Pasteur
Published:Dec 19, 2023
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The identification of microorganisms involved in infection is crucial to ensuring patients receive optimal treatment. Recent epidemics have shown the importance of a tool capable of detecting new or unexpected pathogens and those with rapidly evolving genomes. Currently, the search for infectious agents is mostly targeted and requires prior knowledge of the possible causes of infection. In many cases, however, no microorganism is identified by first-line testing and the cause of the infection remains unknown, leading to suboptimal treatment.

Metagenomics using next-generation sequencing (mNGS) can identify a wide range of pathogens, including rare or novel microorganisms. The study, published recently in The Lancet Microbe, aims to improve the use of this innovative microbial identification technique, which remains complex and costly for hospital laboratories as it requires interdisciplinary skills ranging from specific sample preparation to bioinformatics analysis of a large number of sequences. The Necker-Enfants Malades Hospital (AP–HP) team drew on the technical and IT skills of the Institut Pasteur’s Pathogen Discovery Laboratory to make mNGS available within the AP–HP and to practitioners in healthcare centers in mainland France and overseas.

mNGS for microbial identification

In this study, 742 samples were collected for mNGS analysis from 523 patients between October 29, 201, and November 7, 2022. Samples were accompanied by a mandatory prescription form completed by a clinician, indicating the level of clinical suspicion of infection.

The results relate to a panel whose initial suspicion of infection was either high (63 percent) or low (37 percent). In 117 patient samples (25 percent), where the infection was strongly suspected according to the practitioners’ preliminary assessment, causative or potentially causative pathogens were detected.

The diagnostic yield of mNGS was particularly high in immunocompromised patients and in patients with neurological disorders where brain biopsies were available. In fact, mNGS easily detects a causative or potentially causative pathogenic virus in brain biopsies than in cerebrospinal fluid, which is traditionally used because it is easier to obtain. Furthermore, the study showed that stool analyses could be used to investigate not only digestive disorders but also hepatitis and various neurological symptoms.

Clinical performance of mNGS

In addition, the clinical performance of mNGS compares favorably to conventional microbiology. Together with future studies, the results of this prospective observational study will help to define the role of mNGS in diagnostic and treatment-related decisions.

“This sequencing-based tool is now indispensable for diagnosing patients with a suspected infection. We are now using it earlier and earlier in severe cases, particularly those involving the brain, and in immunocompromised adults and children,” says Olivier Lortholary, MD, PhD, professor, infectious diseases specialist, head of the Department of Infectious and Tropical Diseases at AP–HP, and co-author of the study.

The study also provides insight into the future of infection diagnostics. “The microorganisms we identify with the Necker microbiology laboratory will enable us to develop new tools to make sequencing technology faster and more accessible for frontline microbiological analysis while enhancing its potential for the discovery of new human pathogens,” says co-author Philippe Pérot, PhD, a research engineer in the Pathogen Discovery Laboratory and lead for mNGS at the Institut Pasteur.

- This press release was originally published on the Institut Pasteur website