Metagenomics uses some new terms and techniques, so it’s natural to have questions at the beginning. These FAQs are designed for those new to metagenomics by answering common questions in a way that’s easy to understand.
Yes. Metagenomics looks at all the genetic material in a sample, not just the material from microbes that are already known about. If some of that genetic material does not match known pathogens, it may suggest a new or previously unknown pathogen. This can help when usual tests do not find anything but infection is still suspected. It helped scientists identify SARS-CoV-2, the virus that causes COVID-19.
Clinical metagenomics can be applied to many types of clinical samples such as blood, stool or cerebrospinal fluids, but within the NHS Respiratory Metagenomics Network, we focus specifically on respiratory samples.
These include common samples such as:
- bronchoalveolar lavage (BAL)
- Sputum
- Tracheal aspirates
Respiratory samples can contain a mixture of human cells, background microbes and environmental material. Metagenomics helps make sense of this by analysing all the genetic material present, allowing a wide range of respiratory pathogens to be detected quickly and in a single test.
These tests are already being used across intensive care units across the UK, helping clinicians investigate respiratory infections more rapidly and comprehensively.
A common misconception is that metagenomics sequencing can take days. Traditional culture methods can take several days because the agar plates must be incubated and the microbes given time to grow.
However, our metagenomics workflow can deliver results within one working day.
Here’s why:
- We remove human genetic material from the sample so the genetic material of microbes is easier to detect.
- We used rapid techniques for extracting the genetic material from the microbes and preparing it for sequencing.
- We use nanopore sequencing which can allow real time analysis of the genetic material as soon as it is sequenced.
Within the NHS Respiratory Metagenomics Network, many ICU sites are already using metagenomics to support faster investigations.
Metagenomics tells us what’s in the sample, but interpretation of results is key.
Clinicians and scientists look at factors such as:
How much of the microbe is present
- Whether it fits the patients symptoms
- Whether it’s known to cause disease
- What background or harmless microbes are also there
- Whether it carries AMR genes
- How it compares to similar past cases
In other words, sequencing provides the data but expert interpretation helps provide the answers.
Host depletion is the process of reducing the amount of human DNA or RNA in a sample so that microbial genetic material becomes easier to detect.
Human DNA can overwhelm the signal, especially in respiratory samples, where it often makes up most of what’s present.
It’s a bit like tidying a messy desk, once you clear away the clutter, the important items are much easier to spot.
By reducing human DNA, we make it easier to detect bacteria, viruses, fungi and parasites in the sample.
When a sample is sequenced, it produces millions of fragments of genetic code, made from of DNA or RNA. These pieces are called reads.
On their own, they’re just data, but that’s where bioinformatics comes in. Bioinformatics means using computers and software to make sense of biological information.
The bioinformatics pipeline helps turn those scattered reads into something meaningful through the following steps:
- Quality control: removing low-quality or unreliable reads
- Host depletion: filtering out human DNA so we can focus on the microbes
- Classification: matching each read to known microbes in large databases of known microbes.
- Quantification: estimating how much of each organism is present
- Interpretation: clinicians and scientists review the results to understand what might be clinically relevant.
Together, these steps transform raw sequencing data into a clearer picture of which pathogens are in the sample, helping to support with making diagnoses.
AMR (Antimicrobial resistance) genes are pieces of DNA that help bacteria survive or resist antibiotics.
They act like instructions that teach bacteria, viruses, fungi or parasites how to block an antibiotic, break it down, or push it out of a cell.
If a bacterium has these genes, certain antibiotics may not work as well.
Metagenomics can spot these resistance genes directly from a sample, helping us understand whether harmful bacteria may be harder to treat. This supports better antibiotic choices and helps tackle antimicrobial resistance.
Metagenomics works alongside traditional tests, it doesn’t replace them.
Tests like culture and PCR are still important, especially when clinicians need to:
- Carry out follow-up or targeted testing
- Confirm that a pathogen is present
- Check which antibiotics will work
- Look at the exact strain if needed
Metagenomics adds value by finding pathogens that are hard to grow, unexpected, rare or not covered by routine panel tests. It can also detect pathogens even if the patient has already taken antibiotics.
Together, traditional tests and metagenomics give a much more complete picture of an infection.