The Mars Bar-sized gadget helping NZ scientists decode Covid-19 virus

A Mars Bar-sized device is helping Kiwi scientists speedily unravel the genetic jigsaw of the virus driving the Covid-19 crisis – part of an urgent global effort that could help create a vaccine.

ESR has one of three New Zealand labs now running diagnostic testing on Covid-19 samples, to detect the presence of the virus SARS-CoV-2.

That’s done by searching for small parts of the virus genome – or its genetic make-up – within the samples they’re sent.

But ESR scientists have begun going further by sequencing the entire genomes of the samples, rather than just part of them – something that could reveal much more about how the virus is behaving.

“Different parts of the DNA change at different rates – and analysing the complete genome allows us to get the most accurate picture of the changes that happen,” ESR’s Dr Joep de Ligt told the Herald.

“In viruses, these changes can be used to trace what the origin of the infection is and how it is changing.”

This visualisation shows all of the sequenced SARS-CoV-2 genomes that have been made available through the Nextstrain platform. Image / Supplied
This visualisation shows all of the sequenced SARS-CoV-2 genomes that have been made available through the Nextstrain platform. Image / Supplied

There were now 24 countries sending results from whole genome sequences to The GISAID Initiative, which acts as a publicly-accessible repository for virus sequence data.

And that sharing was critical, as it gave labs around the world new leads about how the virus, which likely came from an animal, managed to enter human cells.

Because New Zealand’s cases were still mostly travel-related, the sequencing was also helping build a localised picture of the outbreaks in those countries where the virus had been picked up.

“Some of those countries might not have the capacity to sequence these cases, due to their immediate outbreak response or less organised health care systems.”

De Ligt, who has been working alongside colleagues Matt Storey and Una Ren, said having whole sequence information meant researchers could delve deeper into the variations in the protein structures they were encoding.

By revealing where these variations were occurring, vaccinologists could then pin-point the best parts of the protein for a vaccine to target.

“A protein that varies a lot is not the best target for a vaccine, as it would only work for some strains,” he explained.

It was just as important to have reliable diagnostic tests.

Overseas, there have already been questions around cases of false-negative Covid-19 test results, which may have been due to the virus having been too small to detect at the time of testing, poor swabbing by doctors, or issues with what’s called the primer.

That’s a section of the virus’ genetic code that binds with the matching code in the virus itself, and scientists try to find a region they don’t think will mutate.

“If the diagnostic primers are in regions that are varying in a certain strain or country, they might become less sensitive or reliable,” he said.

The MinION gene sequencer - seen here compared with a smartphone - has been helping Kiwi scientists unravel the genetic make-up of the virus driving Covid-19. Photo / University of Connecticut
The MinION gene sequencer – seen here compared with a smartphone – has been helping Kiwi scientists unravel the genetic make-up of the virus driving Covid-19. Photo / University of Connecticut

“At times like these, of high uncertainty, you cannot underestimate the importance of good quality data and accurate reporting is crucial to keeping everyone informed and safe.”

The rapid speed of sequencing of virus samples has been a success story overshadowed by the rampant spread of Covid-19 across the world.

Just 20 years ago, sequencing a whole genome was a highly expensive and laborious task.

“Ten years ago, next-generation sequencing was becoming established and sequencing was becoming cheaper, but this still required pure isolates – sometimes hard and lengthy processes – as well as long run times, and was fairly expensive.”

It had only been recent years that efforts like the ARTIC Network – another group focused on fast processing of samples from viral outbreak – had sped things forward.

“The fact that they openly share their protocols and knowledge is allowing the world to respond at unprecedented speed and detail.”

ESR’s own response had been lightning fast. In accordance with World Health Organisation guidelines on testing initial cases, the team generated a complete RNA sequence within two days.

ESR's Dr Joep de Ligt, left, and Matt Storey. Photo / Supplied
ESR’s Dr Joep de Ligt, left, and Matt Storey. Photo / Supplied

That was done using protocols designed by ARTIC, with data being integrated through platforms like Nextstrain.

And there was the MinION – a USB-operated device developed by UK-based technology company Oxford Nanopore Technologies and provided to a select group of researchers around the world.

Incidentally, ESR scientists had already used it for sequencing influenza genes, in anticipation of just such a global event like Covid-19.

“ESR has invested in sequencing and bioinformatics capability, so we’re able to use these great international resources to produce these insights within days and contribute to the global response to this disease.”

How Covid-19 is confirmed

• Labs need to detect the SARS-CoV-2 – the virus causing Covid-19 – from a clinical specimen through a molecular test that picks up genetic material, and then confirm it using a second specific genomic target.

• They can also confirm it by carrying out a pan-coronavirus test – which tests for all strains of the virus including the common cold – and then confirming SARS-CoV-2 through sequencing.

• Cases were also classified in different ways. One was “under investigation” if it had been notified but there wasn’t yet enough information, and “suspect” if it had met both the clinical and epidemiological criteria.

• It became “probable” if both those criteria were met, other possibilities had been excluded, and lab results had turned up suggestive evidence, and finally, “confirmed”, when the lab had definitive evidence.

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