If the pandemic had occurred ten years in the past, what wouldn’t it have seemed like? Likely there would have been many variations, however in all probability probably the most hanging would have been the relative lack of genomic sequencing. That is the place the whole genetic code – or “genome” – of the coronavirus in a testing pattern is rapidly learn and analysed.
At the start of the pandemic, sequencing knowledgeable researchers that they have been coping with a virus that hadn’t been seen earlier than. The fast deciphering of the virus’s genetic code additionally allowed for vaccines to be developed right away, and partly explains why they have been accessible in document time.
Since then, scientists have repeatedly sequenced the virus because it circulates. This permits them to watch modifications and detect variants as they emerge.
Sequencing itself just isn’t new – what’s completely different right now is the quantity going down. Genomes of variants are being examined all over the world at an unprecedented charge, making COVID-19 one of the vital extremely examined outbreaks ever.
With this data we will then observe how particular types of the virus are spreading regionally, nationally and internationally. It makes COVID-19 the primary outbreak to be tracked in close to real-time on a worldwide scale.
This helps with controlling the virus. For instance, along with PCR testing, sequencing helped reveal the emergence of the alpha variant in winter 2020. It additionally confirmed that alpha was quickly changing into extra prevalent and confirmed why, revealing that it had vital mutations related to elevated transmission. This helped inform selections to tighten restrictions.
Sequencing has carried out the identical for omicron, figuring out its regarding mutations and confirming how rapidly it’s spreading. This underlined the necessity for the UK to turbocharge its booster programme.
The street to mass sequencing
The significance of genomic sequencing is simple. However how does it work – and the way has it turn into so frequent?
Effectively, similar to individuals, every copy of the coronavirus has its personal genome, which is round 30,000 characters lengthy. Because the virus reproduces, its genome can mutate barely as a consequence of errors made when copying it. Over time these mutations add up, and so they distinguish one variant of the virus from one other. The genome of a variant of concern might include wherever from 5 to 30 mutations.
The virus’s genome is made out of RNA, and every of its 30,000 characters is one among 4 constructing blocks, represented by the letters A, G, C and U. Sequencing is the method of figuring out their distinctive order. Varied applied sciences can be utilized for this, however a very essential one in getting us to the place we’re is nanopore sequencing. Ten years in the past this expertise wasn’t accessible as it’s right now. Right here’s the way it works.
First the RNA is transformed to DNA. Then, like a protracted thread of cotton being pulled by way of a pinhole in a sheet of material, the DNA is pulled by way of a pore in a membrane. This nanopore is one million instances smaller than a pin head. As every constructing block of DNA passes by way of the nanopore, it provides off a singular sign. A sensor detects the sign modifications, and a pc program decrypts this to disclose the sequence.
Amazingly, the flagship machine for doing nanopore sequencing – the MinION, launched by Oxford Nanopore Applied sciences (ONT) in 2014 – is simply the scale of a stapler; different sequencing methods (corresponding to these developed by Illumina and Pacific BioSciences) typically require cumbersome gear and a well-stocked lab. The MinION is due to this fact extremely transportable, permitting for sequencing to occur on the bottom throughout a illness outbreak.
This primary occurred throughout the 2013-16 Ebola outbreak after which throughout the Zika epidemic of 2015-16. Pop-up labs have been arrange in areas missing scientific infrastructure, enabling scientists to establish the place every outbreak originated.
This expertise laid the muse for sequencing the coronavirus right now. The strategies honed throughout this time, particularly by a genomics analysis group referred to as the Artic Community, have proved invaluable. They have been rapidly tailored for COVID-19 to turn into the idea on which tens of millions of coronavirus genomes have been sequenced throughout the globe since 2020. Nanopore sequencing of Zika and Ebola gave us the strategies to do sequencing at a never-before-seen scale right now.
That stated, with out the a lot bigger capability of the benchtop machines from Illumina, Pacific Biosciences and ONT, we wouldn’t have the ability to capitalise on the data gained by way of nanopore sequencing. Solely with these different applied sciences is it potential to do sequencing on the present quantity.
What subsequent for sequencing?
With COVID-19, researchers have been capable of monitor the outbreak solely as soon as it had began. However the creation of speedy testing and screening programmes for different new ailments, in addition to the infrastructure to conduct widespread sequencing, has now begun. These will present an early warning system to stop the following pandemic taking us abruptly.
As an illustration, sooner or later, surveillance programmes could also be put in place to watch wastewater to establish disease-causing microbes (often called pathogens) current within the inhabitants. Sequencing will enable researchers to establish new pathogens, permitting an early begin on understanding and monitoring the following outbreak earlier than it will get out of hand.
Genome sequencing additionally has a job to play in the way forward for healthcare and medication. It has the potential to diagnose uncommon genetic problems, inform personalised medication, and monitor the ever-increasing menace of drug resistance.
5 to 10 years in the past, scientists have been solely simply starting to trial sequencing expertise on smaller viral outbreaks. The results of the previous two years have resulted in an enormous enhance in using sequencing to trace the unfold of illness. This was made potential by expertise, expertise and infrastructure which have developed over time.
COVID-19 has brought on untold injury worldwide and affected the lives of tens of millions, and we’re but to see its full affect. However current advances – significantly within the discipline of sequencing – have little question improved the scenario past the place we’d in any other case be.
Angela Beckett is affiliated with the COVID-19 Genomics UK Consortium (Cog-UK). She has obtained funding from Analysis England’s Increasing Excellence in England (E3) Fund.
Samuel Robson receives funding from the COVID-19 Genomics UK Consortium (Cog-UK), which is supported by funding from the Medical Analysis Council (MRC), the Nationwide Institute of Well being Analysis (NIHR) and Genome Analysis Restricted. He’s additionally half funded from Analysis England’s Increasing Excellence in England (E3) Fund and has obtained extra funding for COVID analysis from the Wessex Tutorial Well being Sciences Centre (AHSC).