NOV 13, 2024 7:17 AM PST

Metagenomic Sequencing - A Way to ID Nearly Any Pathogen

WRITTEN BY: Carmen Leitch

Scientists developed a genetic tool that can quickly identify nearly any type of pathogenic infection, including those caused by bacteria, fungi, parasite, or virus. This approach can make it easier for clinicians and healthcare providers to care for patients with neurological infections like encephalitis, and can help screen for pathogens that have the potential to cause pandemics. This method relies on metagenomic next-generation sequencing (mNGS), which analyzes all of the genetic material in a sample, including DNA and RNA molecules.

Influenza B virus particles, colorized purple and blue, isolated from a patient sample and then propagated in cell culture. / Credit: Microscopy by John Gallagher and Audray Harris, NIAID Laboratory of Infectious Diseases. / NIAID

This test began a decade ago as an assay to check cerebrospinal fluid (CSF) samples for infections. CSF is a crucial fluid that holds the brain and spinal cord. Over the past decade, this technique has been used to diagnose neurological infections in thousands of patients across the United States. After about 5,000 cases in which the assay was applied, there were infections in about 14 percent of the samples. The assay correctly diagnosed those infections in 86 percent of cases, according to a new study reported in Nature Medicine.

Another study reported in Nature Communications by this team showed that the mNGS technique can now be used to reveal infections in respiratory fluid, such as pneumonia. This test has also been automated, to deliver results even quicker.

"Our technology is deceptively simple," noted senior study author Charles Chiu, MD, PhD, a professor of laboratory medicine and infectious diseases at UCSF. "By replacing multiple tests with a single test, we can take the lengthy guesswork out of diagnosing and treating infections."

The CSF nGS assay is complex, and has over 100 steps that can take two to seven days to complete. However, neurological infections are often quite difficult to diagnose, even while patients continue to get sicker as they wait for an answer. So this test can improve outcomes for many people.

"Our mNGS test performs better than any other category of test for neurologic infections," Chiu said, "The results support its use as a critical part of the diagnostic armamentarium for physicians who are working on patients with infectious diseases."

The adapted test that is used to assess respiratory fluid is much shorter, and has been automated so that robotic machines can do most of the work.

"Our goal was to have the entire process completed within 12 to 24 hours, giving a same-day or next-day result," Chiu said.

The Nature Communications study has demonstrated that the respiratory mNGS test can identify respiratory viruses that could potentially cause a pandemic, such as SARS-CoV-2, influenza A and B, or RSV in under 24 hours. The test can detect even very low levels of virus.

While most genetic tests also need known sequences to reveal all of the species in a sample, this test could also be used to identify novel viruses.

Sources: University of California, San Francisco (UCSF), Nature Medicine, Nature Communications

About the Author
Bachelor's (BA/BS/Other)
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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