How a team at A*Star played a big role in global fight against Covid-19 pandemic

A team from Singapore's A*Star played a major role in setting up and maintaining the database to share and analyse the Covid-19 genomes. ST PHOTO: LIM YAOHUI

SINGAPORE - Singapore has punched above its weight in the fight against the Covid-19 pandemic with the expertise it provided to enable the rapid sharing of genomes of the virus.

This not only helped the World Health Organisation (WHO) and governments around the world to respond faster, but also sped up the development of much-needed vaccines and diagnostic kits.

It has been a year since the first five fully sequenced Sars-CoV-2 virus genomes were made public by laboratories in China via the Global Initiative on Sharing All Influenza Data (Gisaid) on Jan 10, 2020.

Since then, the sequence of more than 360,000 genomes of the virus causing the Covid-19 pandemic, submitted by more than 145 countries, have been shared.

And the team from Singapore's Agency for Science, Technology and Research (A*Star), played a major role in setting up and maintaining the database to share and analyse the genomes.

Under the watch of Dr Sebastian Maurer-Stroh, executive director of the Bioinformatics Institute (BII), it helped to quality check the genome sequences sent in by various countries.

It may not have been the first player in the game, but Gisaid raised the bar.

One non-official sequence was made public in a blog about the same time as Gisaid's but "this was of poor quality and had a portion of human DNA added to the viral sequence", said Dr Maurer-Stroh.

Gisaid prides itself on being meticulous. In January last year, when the number of genomes submitted was small, the curating was done manually. By February, the team in Singapore had developed software to rapidly check the genomes for errors and recruited volunteers, notably from the Genome Institute of Singapore.

Among the more than 20 people who contributed to adapting the flu software to the coronavirus is Mr Raphael Tze, 43, a senior research officer at BII, who worked on a way to check on mutations from the genomes submitted.

Another is a first year computer science student at the University of Waterloo in Canada, Mr Winston Yeo, 21, who spent some months of his holidays here interning with the BII. He was one of 13 students who worked on the project.

He helped cut down the time it took to generate a part of the report from 40 minutes to around 10 minutes.

The software was tweaked over the next few months and can now handle "the avalanche" of genomes coming in, usually in batches of 3,000, Dr Maurer-Stroh said.

The Singapore team also set up the classification of the various clades, or main families the virus belongs to. This allows for analysis, including tracking mutations.

Mr Peter Bogner, president of Gisaid, which is incorporated in Germany, said the work by the BII team has "risen beyond anybody's expectations".

In a phone interview from California, he told The Straits Times: "In a pandemic, we're dealing with a marathon. We need the ability to perform at a very high level, without interruption. It's an entirely different game.

"It's not something that can be rehearsed," he said. "You either succeed, or you don't."

Gisaid president Peter Bogner (left) said the work by the BII team from A*Star, under the direction of Dr Sebastian Maurer-Stroh (right), has "risen beyond anybody's expectations". PHOTOS: COURTESY OF WEFORUM, KUA CHEE SIONG

Today, Gisaid has as many as 45 curators in different time zones around the world working 24/7, and is able to check and add genomes just minutes after they are submitted.

They have all been given access to the software developed by Singapore, which also provides the hardware needed.

Dr Maurer-Stroh said the main annotation server is in Biopolis, and "when there is high demand, we increase the number of servers so the annotation goes faster".

It has also provided a triple back-up on top of the original.

Mr Bogner said the BII team "enabled this immediate ability to process, to curate. Each and every genome that is available in Gisaid actually went through this (the software) physically. Every minute, every second, data is loaded onto Gisaid."

He said the speed, reliability, and the large numbers make the Gisaid database invaluable.

The scientists in Gisaid also have the "technical know-how to interpret the data" to rapidly produce reports which have been given to the WHO's leadership and to governments to help them make decisions "without crystal balling".

WHO chief scientist Soumya Swaminathan said Gisaid was "a game changer" in the fight against the pandemic.

She said in the highly prestigious Nature journal last month: "Since January, Gisaid's data-sharing platform has been the primary source of genomic and associated data from Sars-CoV-2 cases."

The next biggest collection of Sars-Cov-2 genomes is in the United States' GenBank which has about 33,000 genomes and typically takes days to even weeks to check and add new genomes, said Dr Maurer-Stroh. These genomes are also in the Gisaid database.

Professor Tan Chorh Chuan, chief health scientist at the Ministry of Health, said: "Singapore is happy to be able to contribute to the global fight against Covid-19 through the important roles that our researchers are playing in curating the Sars-CoV-2 virus genomic data and viral mutations from all around the world."

He added that Gisaid "has accelerated our understanding of the virus as it spreads, mutates and changes in its infectiousness. It has also been very useful in the development of diagnostic tests, therapeutics and vaccines".

Pfizer and BioNTech, which together produced the first commercially available Covid-19 vaccine, said in the New England Journal of Medicine that work on the vaccine began on Jan 10, 2020 when the first genomes were disseminated globally by Gisaid.

Said Mr Bogner: "There has been contributions from many major institutions, such as the Pasteur Institute in Paris and Fiocruz in Brazil. But one that stands out is the support given by BII and A*Star. It's a shining beacon for us."

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