How DNA Sequencing Can Spot Hard-to-Find Infections?

by Anamika October 25, 2026

When doctors cannot explain a serious illness, finding the germ behind it can become a race against time. Traditional tests usually look for a suspected bacterium or virus. Metagenomic testing takes a wider approach: it reads genetic material in a sample to search for many possible causes at once. It could help doctors solve cases that routine tests miss — although it is not a test that finds every infection.

How the test works

The researchers purify DNA and RNA from the sample (such as fluid around the brain and spinal cord). Genetic fragments are read by sequencing machines, which are then compared to huge databases of microbes in a computer program. The method is able to identify bacteria, viruses, fungi, or parasites, including some that are hard to grow in the lab, and does not require a doctor to first suspect a particular germ. The findings sometimes give an indication of antibiotic resistance, the UK’s NHS Metagenomics Network states.

The strategy caught the world’s attention when it was first used in December 2019 in the unexplained pneumonia outbreak in Wuhan. A team of researchers sequenced the RNA of the patient’s lung fluid using metagenomic RNA sequencing to identify a new coronavirus and thereby help in determining the cause of the outbreak.

When it changes care

The technique itself can be most important when the usual tests fail to yield a response. A woman was diagnosed with liver failure and suspected meningitis, and a fluid test around her brain and spinal cord revealed she had hepatitis E, which was treated and she recovered without a planned liver transplant, as outlined in the report from BBC Future.

The research, published in 2024 in Nature Medicine, evaluated 4,828 spinal-fluid samples from 2016 to 2023. Metagenomic sequencing picked up 48 infections that would not have been detected by the other methods, which were used to review 220 cases of confirmed central nervous system infection in detail. However, it had a sensitivity of 63.1%, which was not detecting all infections.

Promise and limits

While checking and interpreting results may take days, new sequencing devices can read DNA in as little as one to two hours, reports the BBC Future. AI might assist doctors to sift through enormous amounts of data. But seemingly non-threatening microbes and contamination from the lab can skew the findings; human DNA may overwhelm small signals from the microbes; and some organisms are underrepresented in the databases. Also, the test is not always able to differentiate between the actual cause of disease and microbes that are merely in the body.

This is why metagenomic testing is best used in conjunction with doctors’ evaluation and known tests. The possibilities are apparent: if it can extend the search to a different germ, it could be a way for doctors to find answers sooner and for public health officials to locate emerging germs in sewage or air samples before an outbreak happens.