Genome sequencing is reading or decoding the complete genetic information i.e. “Genome” of an organism that is encrypted in the form of a very long string called DNA made up of 4 letters, A, T, G, and C. The genome of an organism essentially determines their physical characteristics and contains information on how the organism develops, functions, and replicates or reproduces. Sequencing the genome of an organism whether it is human, bacteria or virus is an important step towards understanding it. Currently available advanced sequencing technologies can sequence the genome of an organism in the time span of a few hours to a few days depending on the size of the genome. For example, the SARS-CoV-2 virus genome is 30 kilo bases, that includes ~ 12 genes whereas human genome is 3 billion base pairs that includes ~ 30,000 genes. Therefore, the SARS-CoV-2 genome is much smaller than the human genome and can be sequenced much faster.
Genome sequencing is a vital tool that is currently being used to identify and track new emerging SARS-CoV-2 variants. SARS-CoV-2 is an RNA virus that mutates at a rapid rate. Accumulation of these mutations or changes results in a new lineage or sub-lineage of the virus. It is important to note that lot of mutations arise as a virus replicates and evolves over time but most of these mutations have no impact on a variant’s ability to spread or cause infection. However, some mutations that occur on key areas of the genome may give it an advantage like increased transmissibility, enhanced virulence, or allow it to evade recognition by the immune system. For example, spike protein of SARS-CoV-2 directly interacts with receptors on human cells to get entry into cells and cause infection so mutations on the spike protein gene are important and may lead to new lineages. These new lineages commonly called COVID variants have a slightly different genome sequence from their parent’s lineage and have different biological characteristics as well.
Next Generation Sequencing (NGS)
To perform genome sequencing, first genetic material of the virus is isolated from the patient specimen, and then the next generation sequencing (NGS) library is prepared followed by sequencing on genome analyzers called sequencers. Then, genome sequences are processed using bioinformatics analyses and assigned a Pango lineage using the web-based pangolin tool (1). This allows identification and tracking of COVID variants in different geographical regions especially variants that show evidence of clinical significance and are classified as variant of concern (VOC). So far, COVID variants that have been classified as VOCs are B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron).
Since the start of the pandemic, scientists and public health officials have been using genomic surveillance to track new variants and understand how they are being transmitted in the local communities and globally. This kind of information is very useful for public health officials in order to best update public health and travel guidelines, make recommendations to minimize spread of infection and maximize resource allocation. It is crucial that genomic sequence data is made publicly available immediately to guide public health authorities to develop interventions and recommendations for the public in timely manner. The knowledge of new mutations in key regions of the genome is very useful for vaccine developers and scientists to design new vaccines and assess how well available vaccines work on new variants. It could also potentially assist in redesigning available vaccines so that they could better target the emerging variants.
More Variants Emerge
One big question is whether more variants will emerge in the future or if Omicron is the last variant in this pandemic. It is hard for epidemiologists or public health authorities to predict that but considering SARS-CoV-2 is an RNA virus that mutates at a fast rate, it is likely that there will be new variants. One of the characteristics of viruses is that they need host cells to replicate and mutate, therefore they evolve over time. If vaccination rates are high and transmission rates are low, there are fewer opportunities for the virus to replicate and mutate. This slows down evolution of virus and reduces risk of new variants.
Genome sequencing has and will continue to be a vital tool in the fight against SARS-CoV-2.