Synthetic DNA sequences improve genomic analysis

Scientists at the Garvan Institute of Medical Research have led the development of a new technology based on synthetic human genome sequences. Dubbed ‘sequins’ (sequencing spike-ins), the technology has been described in the journal Nature Methods and is now freely available to the academic research community.

Dr Tim Mercer and his team came up with the idea of adding sequins — small stretches of synthetic DNA — to a patient’s DNA sample during sequencing in order to better map and analyse complexity within the genome. He said the technology is based on an intuitively simple concept — the notion of mirror-image DNA.

“Sequins are, essentially, mirror images of natural DNA sequences,” Dr Mercer explained. “Like us, the genome has a ‘handedness’ and, just as our right hand differs from our left hand, sequins differ from natural genome sequences. So sequins behave just like natural genome sequences, but they can be easily recognised as synthetic.”

These sequins act as standards, said Dr Mercer, providing researchers with internal controls with which to assess the sensitivity and accuracy of genome sequencing throughout “a whole series of steps — first in the lab and then on the computer”.

“Sequins are with the person’s DNA every step of the way: responding just as real DNA does at each step, yet unmistakably different from that real DNA,” he said. “This allows a scientist to assess, and optimise, these different steps.”

Because sequins are added to each individual sample, they can provide a sample-by-sample assessment — something that has not previously been possible. Dr Mercer and his team believe their use will “improve the reliability and sensitivity of genetic disease diagnosis” — particularly when it comes to cancer diagnosis.

“Incorporating sequins into clinical tests for cancer diagnosis will increase the reliability of an individual diagnostic readout, reducing incorrect diagnoses and giving clinicians greater confidence in deciding the best course of treatment for their patient,” he said.

Dr Mercer said the technology is freely available to other researchers, making it possible to directly compare genomic data from research institutes and sequencing centres worldwide. “We invite academics to get in touch and we can send them some sequins for their genome research,” he said.

To request sequins for use in your research, visit www.sequin.xyz.

Image credit: Chris Hammang/Garvan Institute of Medical Research.