New DNA Sequencing Method Revolutionizes Metabolite Measurement

Researchers at the University of Toronto have developed a new method for measuring metabolites using DNA sequencing. This approach allows scientists to quickly and accurately analyze biological compounds such as sugars, vitamins, hormones, and other metabolites essential for health.

Their small molecule sequencing platform, called smol-seq, uses short DNA strands known as aptamers to detect metabolites. Each aptamer is designed to bind to a specific metabolite and carries a unique DNA barcode.

“We need to measure metabolites because of the critical role they play in health, but studying such a wide range of molecules is challenging. Until now, mass spectrometry has been the gold standard, but it isn’t as accessible or fast as DNA sequencing-based methods. We wanted to develop a way to detect metabolites using DNA sequencing to take advantage of its incredible power.”

— June Tan, Study First Author and Research Associate, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto

When an aptamer binds to its target metabolite, its structure changes, triggering the release of its DNA barcode. For example, the aptamer that detects glucose releases one specific barcode, while the aptamer for the stress hormone cortisol releases another. By sequencing these released barcodes, researchers can determine which metabolites are present and at what concentrations.

“Aptamers have been used before to measure metabolites, but mostly in ways that only allow a few to be analyzed at a time. We realized that by using DNA barcodes as tags for metabolites, we could measure hundreds or even thousands simultaneously.”

— June Tan

Now that the smol-seq platform is up and running, the research team is focused on developing aptamers for metabolites with biomedical significance. Their long-term goal is to build a comprehensive database of aptamers, which could eventually enable machine learning to predict new aptamer designs for targeting additional metabolites.

Beyond expanding their aptamer library, the researchers—Andrew Fraser, Study Principal Investigator and Professor, University of Toronto—are working to improve the platform’s precision by enhancing the specificity of aptamer binding. As the platform evolves to analyze an even broader range of metabolites, refining these interactions at the nucleic acid level will be essential.

“DNA sequencing is millions of times faster than it was 20 years ago, and we wanted to harness that power for metabolite detection. Smol-seq has the potential to make metabolite analysis as easy and rapid as DNA sequencing itself, which could have a major impact on diagnostics and biotechnology.”
 

— Andrew Fraser, Study Principal Investigator and Professor, University of Toronto

The study was published in Nature Biotechnology.