Researchers have demonstrated the ability to reduce the time it takes to sequence glycosaminoglycan – a class of long-chain sugar molecules as important to our biology as DNA – from years to minutes. In this, the scientists were helped by nanopores.
A team from Rensselaer Polytechnic Institute has proven that machine learning and image recognition software is suitable for quickly and accurately identifying sugar chains – specifically the four synthetic heparan sulfates. Electrical signals are generated as they travel through a tiny hole in a crystal plate. The results are published in the journal Proceedings of the National Academy of Sciences.
Glycosaminoglycans are a complex repertoire of sequences, like Shakespeare is a complex set of letters. An expert is needed to write them, as well as to read them. We trained the machine to quickly read the equivalent of four-letter words such as “ababab” or “bcbcbc”. These are simple sequences that don’t matter. However, they showed that a machine can be taught to read. If we expand and develop this technology, it has the potential to sequence glycans or even proteins in real time without spending years.Robert Linhardt, Principal Investigator and Professor. chemistry and chemical biology at the Rensselaer Polytechnic
Commercial nanopore sequencing devices are used for DNA sequencing. It is made up of four nucleic acid units, known as the letters A, C, G, and T, linked together in an infinite variety of configurations. The device uses an ionic current through a hole in the membrane only a few billionths of a meter wide. DNA strands are placed on one side of the hole and pulled through it with current. Each nucleic acid blocks the hole to some extent as it passes, disrupting the current and giving a specific signal associated with that nucleic acid. The devices now being used for field research are just one of several relatively fast and automated DNA sequencing methods.
Glycosaminoglycans (GAG) are a structurally complex class of glycans. These are essential sugars found in living organisms. They serve a variety of functions in cell growth and signaling, anticoagulation, and wound healing. Today glycosaminoglycans are extracted from slaughtered animals, used as medicines and nutraceuticals.
Like DNA, they can be subdivided into their constituent disaccharide sugar units. But while DNA consists of only four letters in a linear line, glycans have dozens of basic units. Some of them have attached sulfate, acid and amide groups. For example, even a relatively small naturally occurring six sugar unit heparan sulfate molecule may have 32,768 possible sequences. Glycan sequencing remains cumbersome, relying on painstaking laboratory work and sophisticated analysis using techniques such as liquid chromatography and tandem mass spectrometry and nuclear magnetic resonance spectroscopy.