Two research papers from the University of California, San Francisco (UCSF) have reported a novel metagenomic sequencing test that can rapidly diagnose infections from nearly any kind of virus, bacteria, fungus or parasite. The studies, published in Nature Medicine and Nature Communications, demonstrate the applications of the test in identifying neurological and respiratory infections, respectively.
The test developed at UCSF uses metagenomic next-generation sequencing (mNGS) to analyze all the nucleic acids, including DNA and RNA, that are present in a sample. This enables the identification of any pathogen present in the sample, eliminating the need to look for one type of pathogen at a time.
“By replacing multiple tests with a single test, we can take the lengthy guesswork out of diagnosing and treating infections,” said senior author Charles Chiu, MD, PhD, professor of laboratory medicine and infectious diseases at UCSF. “The test has the potential to vastly improve care for neurological infections that cause diseases like meningitis and encephalitis, as well as speed up the detection of new viral pandemic threats.”
The metagenomics test was originally developed to aid in the diagnosis of neurological diseases, which can be especially hard to identify when they are caused by a rare or previously unknown pathogen. The test works by first sequencing all the genetic material found in the cerebrospinal fluid, and then running a computational analysis to separate human sequences from those of pathogens.
The first clinical application of the test was in 2014, when it was used to treat a young boy who was critically ill with an undiagnosed infection. While all previous tests had failed, the metagenomics test was able to diagnose the infection, which led to the full recovery of the patient.
Since then, the test has been in routine use at UCSF, with multiple hospitals across the country sending samples to be tested. The study published in Nature Medicine details the analysis of nearly 5,000 samples of cerebrospinal fluid between 2016 and 2023, of which 14% were diagnosed with an infection. The metagenomics test was then able to correctly identify the pathogen in 86% of those samples.
“Our mNGS test performs better than any other category of test for neurologic infections,” said Chiu. “The results support its use as a critical part of the diagnostic armamentarium for physicians who are working up patients with infectious diseases.”
Chiu and colleagues have founded a company named Delve Bio to increase access to the technology by acting as the exclusive provider of the cerebrospinal fluid test, which has also received breakthrough device designation from the FDA for both of its applications.
In the companion Nature Communications study, the metagenomics test was adapted to work with samples of respiratory fluid to identify pathogens that can cause pneumonia. Here, the researchers used automation to significantly reduce the time it takes to complete the test.
“Whereas the [cerebrospinal fluid] test entails more than 100 separate steps and can take two to seven days to process, the respiratory test requires just 30 minutes of hands-on time before robots and algorithms can take over,” Chiu explained. “Our goal was to have the entire process completed within 12 to 24 hours, giving a same-day or next-day result.”
The study demonstrated that the test could detect viruses with pandemic potential, such as SARS-CoV-2, influenza A and B, and respiratory syncytial virus, even when only small amounts of virus were present in the sample. The metagenomics test was also proven able to detect newly evolved strains, should they emerge in the future.
