Images of the delta and omicron variants of SARS-Cov-2

Blog

24 Mar 2022

Exploring the mutational world of SARS-CoV-2

 A recent publication from the consortium describes the creation of the COG-UK-Mutation Explorer, a tool that researchers have used to explore mutations in the UK’s SARS-CoV-2 genomic data and to understand how the patterns of mutations observed affect antigenicity and resistance to drug and antibodies.

Like the COVID-19 Genomics UK (COG-UK) consortium itself, the COG-UK-Mutation Explorer (COG-UK-ME) tool was born out of urgent scientific and medical need during the COVID-19 pandemic. While extensive SARS-COV-2 data processing, variant calling and mutation profiling was being carried out on CLIMB-COVID by COG-UK members, this was not accessible to the general public. Derek Wright, a bioinformatician at the MRC-University of Glasgow Centre for Virus Research and lead developer for the project, says “in late-2020, with colleagues on the COG-UK Mutational Analysis Working group led by Dr Alessandro Carabelli, we started producing online reports for COG-UK focused on mutations of interest that needed to be tracked. It made sense to develop these reports into an interactive dashboard, so we had that up-and-running in early-February 2021 – we’ve continually added features to it since.”

The COG-UK-ME tool uses genomic sequencing data to track changes in the SARS-CoV-2 genome, which allows us to identify evolutionary signals associated with mutations of known importance, either from the experimental literature or linked to clinical outcomes and/or vaccine effectiveness. Several other essential web resources for tracking SARS-CoV-2 exist, but these focus on epidemiological aspects of the pandemic and there were none that capture the antigenic effects of mutations and link this data to a nation’s circulating variants in near real-time. As Derek puts it, “We wanted to link the mutational data with the studies relating to antigenicity, which means monitoring mutations responsible for the immune response, as well as mutations that may be accumulating relating to drug resistance or monoclonal antibody treatments. For example, using COG-UK-ME we were quickly able to assess the mutations present in the Omicron BA.1 variant and determine that it was likely to be less susceptible to neutralising antibodies owing to vaccination or prior infection, which was borne out by subsequent laboratory analyses.”

Since its launch during the Alpha wave at the beginning of 2021, the team behind the COG-UK-ME tool have received enquiries and positive feedback from journalists, public health workers and scientists alike. “There seems to be quite a wide range of people using COG-UK-ME, both within research and outside in the wider community,” Derek tells us. Another clear demonstration of its usefulness and impact can be seen in analysing site traffic. At the time of writing, the tool hosts around 5,000 unique users per month, though this number can sometimes be much higher. “We get surges of interest sometimes, like when Omicron emerged, we got a spike in hits with many people interested in the latest data updates.”

In terms of widening the COG-UK-ME tool’s impact, in the future the team will be focused primarily on two key updates. The first priority is to expand the tool to include genome sequences from other countries, and the second is to develop COG-UK-ME as more of an analytical platform. At the moment the tool mostly presents counts of genome sequences, mutations, and variants linked to curated knowledge, providing users with a snapshot of the data that’s currently available in COG-UK’s dataset. Going forward, the team aims for users to be able to better interrogate the data presented, for instance by visualising variation and its nature in protein structural context.

Derek also emphasises that the COG-UK-ME tool’s current functionality is what makes it such a relevant tool. “It’s an exploratory tool and there isn’t really ‘one single thing’ that everyone will take away from it. This will vary depending on the user’s background and the interests that they have.” The ethos underpinning the COG-UK-Mutation Explorer is in the name, after all. Derek says, “We want users to be able to explore SARS-CoV-2 mutation data and we provide an entry point for that.”

 

Read the full publication and results here.

 


COVID-19 Genomics UK (COG-UK)

The COVID-19 Genomics UK (COG-UK) consortium works in partnership to harness the power of SARS-CoV-2 genomics in the fight against COVID-19.

Led by Professor Sharon Peacock of the University of Cambridge, COG-UK is made up of an innovative collaboration of NHS organisations, the four public health agencies of the UK, the Wellcome Sanger Institute and sixteen academic partners. A full list of collaborators can be found here.

The COVID-19 pandemic, caused by SARS-CoV-2, represents a major threat to health. The COG-UK consortium was formed in March 2020 to deliver SARS-CoV-2 genome sequencing and analysis to inform public health policy and to support the establishment of a national pathogen sequencing service, with sequence data now predominantly generated by the Wellcome Sanger Institute and the Public Health Agencies.

SARS-CoV-2 genome sequencing and analysis plays a key role in the COVID-19 public health response by enabling the identification, tracking and analysis of variants of concern, and by informing the design of vaccines and therapeutics. COG-UK works collaboratively to deliver world-class research on pathogen sequencing and analysis, maximise the value of genomic data by ensuring fair access and data linkage, and provide a training programme to enable equity in global sequencing.