Genome sequencing: Here’s how researchers identified omicrons and other COVID-19 variants

By Andre Hudson, Rochester Institute of Technology and Crista Wadsworth, Rochester Institute of Technology

How do scientists detect new variants of the virus that causes COVID-19? The answer is a process known as DNA sequencing.

Researchers sequence DNA to determine the order of the four chemical building blocks, or nucleotides, that make up it: adenine, thymine, cytosine, and guanine. These millions to billions of building blocks are pieced together to form a genome that contains all the genetic information an organism needs to survive.

When an organism clones, it makes a copy of its entire genome to pass on to its descendants. Sometimes errors during replication can lead to mutations where one or more building blocks are swapped, deleted, or inserted. This can alter the genes, the instruction pages for the proteins that enable an organism to function, and can ultimately affect the organism’s physical characteristics. For example, in humans, eye and hair color are the result of genetic variations that can arise from mutations. In the case of the virus that causes COVID-19, SARS-CoV-2, the mutation could change its ability to spread, cause infection, or even evade the immune system.

We are both biochemists and microbiologists teaching and researching the bacterial genome. We both used DNA sequencing in our research to understand how mutations affect antibiotic resistance. The tools we use to sequence DNA in our work are the same as those that scientists are using today to study the SARS-CoV-2 virus.

The first human genome took two decades to sequence. With advances in technology, scientists can now sequence DNA in a matter of hours.

How is the genome sequenced?

One of the earliest methods scientists used in the 1970s and 1980s was Sanger sequencing, which involves cutting DNA into short fragments and adding radioactive or fluorescent tags to identify each nucleotide. The fragments are then passed through an electric sieve to sort them by size. Compared to newer methods, Sanger sequencing is slower and can only handle relatively short DNA fragments. Despite these limitations, it provides highly accurate data, and some researchers are still actively using this method to sequence SARS-CoV-2 samples.

Since the late 1990s, next-generation sequencing has revolutionized the way researchers collect data and make sense of the genome. Called NGS, these technologies can process much higher volumes of DNA at once, dramatically reducing the time it takes to sequence a single genome.

There are two main types of NGS platforms: second and third generation sequencing.

Second generation sequencing marks each nucleotide with a specific color.

Second generation technology can read DNA directly. After the DNA is cut into fragments, short pieces of genetic material called adapters are added to give each nucleotide a different color. For example, adenin is blue and cytosine is red. Finally, these DNA fragments are fed into a computer and assembled into whole genome sequences.

Third generation technologies such as Nanopore MinIon directly sequence DNA by passing the entire DNA molecule through an electrical hole in the sequencer. Because each pair of nucleotides disrupts the current in a specific way, the sequencer can read these changes and upload them directly to the computer. This allows physicians to sequence samples in treatment and point-of-care facilities. However, Nanopore sequenced the DNA volume was smaller than that of other NGS platforms.

Third generation sequencing detects changes in electrical current for nucleotide identification.

Although each class of sequence processes DNA in a different way, they can all report millions or billions of building blocks that make up the genome in short periods of time – from hours to days. For example, the Illumina NovaSeq can sequence about 150 billion nucleotides, or 48 human genomes, in just three days.

Using sequence data to fight coronavirus

So why is genome sequencing such an important tool in fighting the spread of SARS-CoV-2?

Rapid public health responses to SARS-CoV-2 require in-depth knowledge of how the virus changes over time. Scientists have used genome sequencing to track SARS-CoV-2 in near real-time since the start of the pandemic. Millions of individual SARS-CoV-2 genomes have been sequenced and stored in various public repositories such as the Global Initiative for Avian Influenza Data Sharing and the Information Center. National Biotechnology.

Genomic surveillance has guided public health decisions as each new variant emerges. For example, sequencing the genome of the omicron variant allowed the researchers to detect more than 30 mutations in the mutant protein that allows the virus to bind to cells in the human body. This makes omicron a variant of concern, as these mutations are known to contribute to the virus’ ability to spread. Researchers are still learning about how these mutations might affect the severity of infections caused by the omicron and how well it evades current vaccines.

Sequencing has also helped the researchers identify variants that spread to new regions. Upon receipt of a sample of SARS-CoV-2 collected from a traveler returning from South Africa on November 22, 2021, researchers at the University of California, San Francisco, were able to detect the presence of the virus. representation of omicrons in 5 h and has almost the entire genome sequenced in eight. Since then, the Centers for Disease Control and Prevention has been monitoring the spread of omicrons and advising the government on ways to prevent widespread community spread.

The rapid discovery of omicrons worldwide underscores the power of powerful genomic surveillance and the value of sharing genomic data globally. Understanding the genetic makeup of the virus and its variants gives researchers and public health officials a deeper understanding of how best to update public health and Maximize resource allocation for vaccine and drug development. By providing essential information on how to limit the spread of new variants, gene sequencing has saved and will continue to save countless lives during the course of a pandemic.

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Andre Hudson, Professor and Dean of the Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology and Crista Wadsworth, Assistant Professor at the Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology

This article is republished from The Conversation under a Creative Commons license. Read the original article.


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