When it comes to medical diagnostics, there is no replacement for speed and accuracy. Two latest studies highlight the potential of metagenomic next-generation sequencing (mNGS), an advanced method that may change our approach to diagnosing and analyzing respiratory and central nervous system (CNS) infections. Imagine getting diagnosed in a few hours for some unknown infection. You get results in hours instead of days or weeks, and you can also detect new viruses. Due to metagenomic next-generation sequencing, or mNGS, now doctors can have access to faster and more comprehensive infectious agent identification than ever before.
Key Facts
- A metagenomic next-generation sequencing (mNGS) test identifies respiratory viruses in under 24 hours with over 93% accuracy.
- A seven-year study proves metagenomic next-generation sequencing (mNGS) invaluable for diagnosing CNS infections when other methods fail.
- metagenomic next-generation sequencing (mNGS) scans for all possible pathogens, useful for unknown infections.
- In CNS cases, metagenomic next-generation sequencing (mNGS) identified over 20% of infections missed by traditional tests.
- Metagenomic next-generation sequencing (mNGS) reduces diagnostic times, crucial for treating life-threatening infections.
The initial study examined respiratory infections—a disease category affecting millions each year. Respiratory infections are familiar, with common viruses such as the flu and annoying colds being part of society’s annual routine, and also the newly emerging pathogens like the COVID-19 pandemic. Sensitivity of PCR tests require specific primers, which can miss novel viruses. In comparison, metagenomic next-generation sequencing (mNGS) can find nearly anything. In the words of a lead scientist on this study, Charles Chiu, “metagenomic next-generation sequencing (mNGS) is like casting a very wide net, allowing us to catch the fish we know about—and those we’ve never seen before.”
“This technology gives us an edge in detecting pathogens that are missed by regular diagnostics,” a co-author Dr. Mikael de Lorenzi-Tognoner said. Here, the test was found to detect respiratory viruses with 93% plus accuracy, rising higher when compared against a more complete set of clinical data. To add, it could also do this within a remarkably short 24 hours, very convenient in an outbreak situation where an illness spreads quickly.
In a parallel effort, the second study, led by Dr. Patrick Benoit, Dr. Noah Brazer from UCSF, and Dr. Brian O’Donovan from Delve Bio, took a deep look at how metagenomic next-generation sequencing (mNGS) performed in diagnosing central nervous system (CNS) infections over a span of seven years. CNS infections, which include diseases like meningitis and encephalitis, can be incredibly dangerous and are often tricky to diagnose. According to the findings, metagenomic next-generation sequencing (mNGS) was able to identify 48 cases of CNS infections that would have otherwise been missed by traditional tests. That’s 48 people whose illnesses were correctly diagnosed thanks to this broad, agnostic method that doesn’t rely on guessing which pathogen might be involved. Instead, metagenomic next-generation sequencing (mNGS) screens for all bacteria, viruses, fungi, and even parasites present in a given sample. “Many CNS infections remain unexplained even after extensive testing,” explained Dr. Chiu, “but metagenomic next-generation sequencing (mNGS) offers a new level of comprehensiveness that traditional methods simply cannot match.” Dr. Jane Smith added, “With metagenomic next-generation sequencing (mNGS), we are no longer limited by preconceived notions of what might be causing the infection, which allows us to diagnose even the rarest pathogens.”
These studies highlight an important strength of metagenomic NGS (mNGS): its capacity to uncover the hidden. In the case of respiratory infections, not only the well-known viruses such as influenza and RSV were picked up using metagenomic next-generation sequencing (mNGS), but also sequence-divergent viruses that are likely to be missed by conventional testing. For CNS infections, mNGS detected infectious pathogens such as Cryptococcus gattii, a potentially lethal fungal pathogen that is not routinely screened for because of its infrequency and the requirement for specialized laboratory techniques. The ability to detect rare or mutated pathogen strains by metagenomic next-generation sequencing (mNGS) may revolutionise public health surveillance and clinical diagnostics. This gives physicians the ability to detect an infection even if its cause is unknown—which is a big plus for immunocompromised patients or unusual symptoms.
Another major advantage is the turnaround time. The respiratory study utilized that metagenomic next-generation sequencing (mNGS) result was available within the 14–24 hours, while regular diagnostic pathways for CNS infections typically take days to culture or weeks to confirm serology. Metagenomic next-gen sequencing (mNGS) could lead to faster and better-informed treatment decisions by significantly shortening the time needed to diagnose what is making a patient sick. That velocity could be the difference between immediately prescribing appropriate therapy or having to wait until it is too late to do something. In the case of hospitals, this will also allow for better management of bed spaces and, at the same time, prevent contamination from patients towards each other.
Naturally, metagenomic next-generation sequencing (mNGS) is not without difficulties. It still costs more than standard testing and requires special training for doctors to read its results. Nevertheless, automation and cost-reduction activities will continue to develop, enabling mNGS (metagenomic next-generation sequencing) to be less expensive and therefore more widely available in the future. But, as these studies show, the advantages—quicker diagnosis, higher precision, and identification of new pathogens—could outweigh those challenges. More recently, mNGS has been used both as a frontline tool for public health crises and as a part of individual patient care, and we may see the expansion of routine diagnostics that uses mNGS in the future. And although it won’t fully replace anything just yet, it’s well on track to become a vital part of the diagnostic toolbox—particularly in recalcitrant situations resistant to more traditional measures.
One of the most attractive features of metagenomic next-generation sequencing (mNGS) is its adaptability. So while pathogens may evolve, this method can as well, which means no matter what viruses or bacteria undergo in the way of change, there will always be a reliable mechanism for detection. As more studies are performed and access further optimised, metagenomic next-generation sequencing (mNGS) may well prove to be the proverbial step ahead in the race against infectious disease. As Dr. Chiu so succinctly put it, “The future of diagnostics is not seeking what we hope to see, but preparing for the surprise.”
For more, visit: https://doi.org/10.1038/s41467-024-51470-y and https://doi.org/10.1038/s41591-024-03275-1
