The global impact of the COVID-19 pandemic has demonstrated why we need sophisticated genomic surveillance processes in place to identify Variants of Concern quickly and efficiently. We spoke to Dr Matthew Bashton, Vice-Chancellor’s Senior Fellow at the Northumbria University’s Department of Applied Sciences, about the development of Systematic ProtEin AnnotatoR (SPEAR), a breakthrough genomic surveillance discovery tool.
At the height of the pandemic, research labs across the UK worked strenuously to analyse a high volume of samples every day, trying to keep tabs on the different variants of SARS-CoV-2 emerging across the country. Research teams initially analysed these samples manually, but it quickly became clear that we would need a more sophisticated system in order to alert public health officials and policy makers of highly infectious variants.
Variants of Concern (VoCs) are defined by health authorities reactively, based on their relative ability to lead to significant negative changes at the global public health level (i.e., a notable increase in transmissibility, virulence or a decrease in effectiveness of public health measures). Only then is the VoC labelled in sequencing outputs so that transmission can be closely monitored. Matthew and his team saw that there was a need to identify potential VoCs directly from sequencing data – helping to speed the process up and quickly identify new potential VoCs. This would be particularly important as we moved towards SARS-CoV-2 becoming endemic, with transmission remaining relatively high but the volume of testing, and therefore genome sequencing, likely decreasing over time.
“We needed to capture all protein products that were produced by each variant to quickly detect mutations in genetic sequences, and give meaning to them,” says Matthew, “there were loads of protein structures that were not being accounted for, which we knew would help with studying the virus.”
Matthew developed the Systematic ProtEin AnnotatoR (SPEAR) tool, through funding provided by COG-UK, and with the assistance of Matthew Crown, PhD student at Northumbria University’s Department of Applied Sciences. “The tool works to inform rapid detection of mutations that could be problematic,” explains Matthew, “it’s about shortening the time from detection to public health action.”
SPEAR was built from a range of existing tools, and uses information from protein structure, deep mutational scanning and computational molecular biophysics – providing a comprehensive protein product annotation for SARS-CoV-2. This data provides insights that help to predict and identify potential VoCs. “These inputs have helped create a data set which maps all the residues (two or more amino acids bond with each other) in each protein that have a biological function and contribute to the overall protein structure of the virus,” says Matthew.
To identify mutation patterns in the proteins, each affected residue is assigned a label. When looked at collectively, the labels are used to calculate ‘scores’ for the mutations. “Through these scores, we can see how much of a worry a variant could be,” says Matthew.
“Lots of mutations doesn’t necessarily mean that a variant is a cause for concern,” explains Matthew, “what’s important is the quantitative measures that tell us the variant’s potential for immune escape and transmissibility. It’s about being more intelligent in the way we describe and annotate the virus and understanding what the detected mutations mean.”
“Had we run the sequences of the Omicron variant through SPEAR at the time, we would have immediately seen that it was a big step-change, which would have alerted us to its potential much sooner,” reflects Matthew. When the team retrospectively ran Omicron through SPEAR, it scored higher for immune escape than both the Alpha and Delta variants. This would have immediately drawn attention to the possibility of a new threat.
Matthew concludes, “Looking to the future, I believe tools like SPEAR that use functionally driven annotation at the point of sequencing can help to improve responses to other viruses and as such should be prioritised. Surveillance genomics technologies should be vital components for us to have in our arsenal in anticipation of future pandemics.”
The SPEAR tool is available for use and can be found here.
Read the full publication here.
