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The Devil is in the Details: How Genome Sequencing Can Help Address Viral Pandemics

25 Aug 2021

Undeniably, the year 2020 was an unprecedented one, full of uncertainty and turmoil. The COVID-19 pandemic wreaked havoc on the world healthcare systems, crippled infrastructure and toppled economies. Good or bad, the fact that the post-COVID world won’t remain the same is unequivocal. Its effect on the human civilization, especially the health of the masses and the entire approach towards healthcare, has been climacteric and will resonate for many more years to come.

While the world battled a never-seen-before health crisis, healthcare experts, zoologists, wildlife biologists, and microbiologists made immense progress with their research. It’s pertinent to note that it did not take even a year to develop the first COVID-19 vaccine. All thanks to the doctors and scientists who worked tirelessly and came out with the complete genome sequencing of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) – the causative agent of COVID-19 (by the end of January 2020).

The recent advances have now enabled the scientists to sequence the genomes of the virus in real-time. Let’s understand the concept of genome sequencing and its importance in addressing the ongoing Covid situation and pathogens that can cause epidemics of a similar scale in the future.

Genome Sequencing

Genes are the basic unit of heredity in a sequence of nucleotides in DNA or RNA. Genome sequencing, as the name suggests, is the sequencing of the entire genome of an organism. It provides the molecular blueprint of an organism and helps scientists study how the genes of an organism work together in its growth and development.

The Corona, Ebola, Zika, and SARS viruses carry their genes in RNA form that is easy to replicate and spread.

Methods of Genome Sequencing

Frederic Sanger was the first person to develop the DNA sequencing technique in 1977. However, sequencing was not an easy task back then, considering the lack of technology and amount of data extracted from the DNA.

Following are the different methods used in genome sequencing:

Clone-by-clone: Breaking the genome into large chunks (clones), finding where the clone belongs in the genome, cutting each clone into smaller, overlapping pieces and sequencing the pieces to replicate the original sequence

Whole-genome shotgun: Breaking the genome into small pieces, sequencing the pieces, and reassembling them.

The reassembling of the pieces in both the methods is done either through de novo assembly or assembly by reference mapping. De novo assembly identifies overlapping regions, aligns the sequence, and puts them back together. On the other hand, assembly by reference mapping uses another genome as a reference point to align new sequencing data.

Genome sequencing reached new levels when the Human Genome Project was proposed for large-scale sequencing in 1990 and was completed in 2003. This became possible due to the advent of advanced computers that could process the data effectively and quickly.

Since then capabilities have further increased and the next-generation sequencing technologies can finish 13 years of work in a few weeks. It has also led to a reduction in the costs incurred.

As a result, more than 1 million coronavirus genome sequences from 172 countries and territories have now been shared on a popular online data platform.

Importance of Genome Sequencing

You must have heard or read about various variants of the coronavirus, viz. Alpha, Beta, Gamma, Delta; These are the “variants of concern”. The other variants, currently, in the “variants of interest” category are Eta, Iota, Kappa, and Lambda.

The variants of concern have shown greater transmissibility, change in epidemiology, increase in virulence and decrease in the effectiveness of health, diagnostics, vaccines, and therapeutics. The variants of interest are the variants that have been identified as potential threats that may cause severe community transmission in the future and are not currently prevalent.

Coronaviruses carry their gene in RNA form. RNA viruses are small and have the ability to multiply and spread quickly. In the absence of a proofreading mechanism, unlike DNA viruses, RNA viruses on duplication are most likely to mutate. Coronaviruses have an enzyme that fixes the duplication mistakes, making mutation slower but more harmful. Our immune systems may not be able to recognize the mutated virus, therefore, rendering drugs and vaccines less effective.

How do we know so much about the virus and its variants? Genome sequencing is the answer.

Genome sequencing gives us the insights needed to better plan our health responses to viruses. As mentioned above, each variant comes with its share of challenges. Therefore, the whole purpose of sequencing is to improve diagnostics, countermeasures and disease epidemiology.

The current pandemic situation warrants that countries must work together to share data, fund their labs carrying these studies, and work to establish national Biosafety Level (BSL) 3 and Level 4 laboratories. We also need to identify the computational architecture required to process and store data.

It is on the back of genome sequencing that we have been able to move ahead in the fight against the disease. The only learning we can take forward is to continue improving R & D in genomics to find out more about the notorious pathogens that can cause trouble in the future and be better prepared.

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