Single genetic test can identify multiple pathogens and can be used by the UCSF clinical laboratory team to help physicians identify difficult to diagnose diseases
Continuing improvements in gene sequencing technologies and analytical software tools are enabling clinical laboratorians to diagnosis patients who have challenging symptoms. One such example is a new genomic test developed by researchers at University California, San Francisco (UCSF). The single test analyzes both RNA and DNA to detect almost any type of pathogen that may be the cause of specific illnesses.
The test uses a genomic sequencing technique known as metagenomics next-generation sequencing (mNGS). It works by sequencing genetic material found in blood, tissue, or body fluid samples and compares the sequenced data against a broad database of known pathogens to seek a match. Instead of looking for just one pathogen at a time, mNGS analyzes all of the nucleic acids, RNA, and DNA present in a sample simultaneously to detect nearly all pathogens, including viruses, bacteria, fungi, and parasites.
The mNGS test is not intended to replace existing clinical laboratory tests, but to help physicians diagnose an illness in cases where patients are experiencing severe symptoms, and where initial, commonplace tests are ineffective. In such cases, medical professionals require additional information to achieve a proper diagnosis.
A pair of studies released late last year outlined the specifics and success of the technology. They are “Seven-year Performance of a Clinical Metagenomic Next-generation Sequencing Test for Diagnosis of Central Nervous System Infections,” published in Nature Medicine, and “Laboratory Validation of a Clinical Metagenomic Next-generation Sequencing Assay for Respiratory Virus Detection and Discovery,” published in Nature Communications. Both articles were released on November 12, 2024.
“Our technology is deceptively simple,” said Charles Chiu, MD, PhD (above), professor of laboratory medicine and infectious diseases at UCSF and senior author of the studies in a news release. “By replacing multiple tests with a single test, we can take the lengthy guesswork out of diagnosing and treating infections.” The new technology may help physicians diagnose patients who have challenging symptoms and where current clinical laboratory testing is ineffective at identifying specific pathogens. (Photo copyright: University California San Francisco.)
Diagnostic Armamentarium for Physicians
According to an article published by the American Society for Microbiology (ASM) titled, “Metagenomic Next Generation Sequencing: How Does It Work and Is It Coming to Your Clinical Microbiology Lab?” mNGS is “running all nucleic acids in a sample, which may contain mixed populations of microorganisms, and assigning these to their reference genomes to understand which microbes are present and in what proportions. The ability to sequence and identify nucleic acids from multiple different taxa [plural for taxon] for metagenomic analysis makes this a powerful new platform that can simultaneously identify genetic material from entirely different kingdoms of organisms.”
The researchers developed the mNGS test years ago and it has produced promising results, including:
- Diagnosing cases of encephalitis in transplant recipients to yellow fever in their organ donors.
- Helping to identify the cause of a meningitis outbreak in Mexico among surgical patients.
- Detecting a case of leptospirosis in a patient who was in a medically induced coma, which prompted doctors to prescribe penicillin and resulted in the full recovery of the patient.
- Identifying the cause of neurological infections such as meningitis and encephalitis. The test successfully diagnosed 86% of neurological infections in more than 4,800 spinal fluid samples.
“Our mNGS test performs better than any other category of test for neurologic infections,” said Charles Chiu, MD, PhD, professor of laboratory medicine and infectious diseases at UCSF and senior author of the two studies, in a UCSF news release. “The results support its use as a critical part of the diagnostic armamentarium for physicians who are working up patients with infectious diseases.”
FDA Breakthrough Device Designation
The UCSF test has not yet been approved by the federal Food and Drug Administration (FDA), but it was granted a “breakthrough device” designation by the agency. This classification authorizes labs to use the test as a valid diagnosis method due to its potential ability to benefit patients.
Chiu told NBC News that the test costs about $3,000 per sample and fewer than 10 labs routinely use it due to several issues.
“Traditionally, it’s been used as a test of last resort, but that’s primarily because of issues involving, for instance, the cost of the test, the fact that it’s only available in specialized reference laboratories, and it also is quite laborious to run,” he said.
This type of lab testing is not feasible for most hospitals as it is costly and complicated, and because physicians may need assistance from clinical laboratory personnel who have the appropriate expertise to properly read test results.
“This just is not something that a clinical lab will be doing until somebody commercially puts it in a box with an easy button,” Susan Butler-Wu, PhD, associate professor of clinical pathology at the University of Southern California (USC), told NBC News. “It’s not a one-stop shop. It just can be helpful as an additional tool.”
Although the technology has some limitations, Chiu says the research performed by his team “raises the possibility that we perhaps should be considering running this test earlier” in symptomatic patients. He hopes the test will be used on a widespread basis in hospitals to diagnose various illnesses in the future.
“We need to get the cost down and we need to get the turnaround times down as well,” he told NBC.
Definitive Tool for Pathogen Detection
To increase access to the technology, Chiu and his colleagues founded Delve Bio, which is now the exclusive provider of the mNGS tool created at UCSF. In December, the company announced the commercial launch of Delve Detect, a metagenomic test for infectious diseases. According to its website, Delve Detect “offers genomic testing of cerebrospinal fluid (CSF) for more than 68,000 pathogens, with 48-hour turnaround time and metagenomics experts readily available to discuss results.”
“These findings support including mNGS as a core tool in the clinical workup for CNS [central nervous system] infections,” said Steve Miller, MD, PhD, UCSF volunteer clinical professor, laboratory medicine, and chief medical officer of Delve Bio in the UCSF news release. “mNGS offers the single most unbiased, complete and definitive tool for pathogen detection. Thanks to its ability to quickly diagnose an infection, mNGS helps guide management decisions and treatment for patients with meningitis and encephalitis, potentially reducing healthcare costs down the line.”
This mNGS test may prove to have the potential to greatly improve medical care for some infections and possibly expedite the detection of new viral threats. It is probable that clinical laboratories will soon be learning about and performing more tests of this nature in the future.
—JP Schlingman
Related Information:
Cutting-edge Test Uses DNA Sequencing to Yield Diagnoses for Some Medical Mysteries
One Genomic Test Can Diagnose Nearly Any Infection
Rapid Test Can ID Unknown Causes of Infections Throughout the Body
Delve Bio Announces Launch of its Groundbreaking Genomic Infectious Disease Test, Delve Detect