Genomics to the rescue!
Pharmacogenomics
Developments in genomics have given rise to many specialised domains of deep research. It has accelerated the identification of novel drug targets in genome related studies, i.e. in the processes of targeting, discovery and validation of drugs. On the other hand, it has facilitated the identification of drug-risk profiles in early preclinical developments by way of creating molecular go/no-go decision gates, i.e. toxicogenomics. Genomics has also stimulated the development of novel multivariate signature assays, thereby paving the way for improved molecular diagnostics test and personalised medicine.
Another promising domain is that of pharmacogenomics. It is the science that allows us to predict a response to drugs based on an individual’s genetic makeup. It helps in monitoring the rate of disease occurrence, the risk of disease progression or recurrence, the drug or drug class most likely to provide benefit, the therapeutic dose, the nature and extent of beneficial responses to treatment and the likelihood of drug toxicity. Apart from improving the clinical management, it may also reduce the costs of clinical trials as it can enhance the stratification of patients enrolled in latestage drug development. This would enable risk mitigation for pharma companies by avoiding losses due to drug failures after a substantial expenditure has already been invested on drug development. This is specifically important in drug development for diseases that do not have a huge paying market, e.g., tuberculosis, malaria and other neglected tropical diseases.
Genomics in India
India too launched its own genomic sequence initiative, the Indian Genome Variation Project (IGV) in 2003 to assess the genetic variation of its population. The findings were interesting as this was the first time the Indian population was categorised according to their genetic map. The study showed that certain (functional) alleles, i.e., gene variants of diseaseassociated genes, had distinct distribution frequencies across the groups studied. This stratified the population further according to disease susceptibility.
The Pandemic
SARS-CoV-2 whole genome was published in January 2020 after which various diagnostic, therapeutic and vaccine efforts were launched. The coronavirus variants were spreading and with the help of genomic technologies it was possible to track and monitor how the variants were emerging and spreading.
The start of 2021 brought the onset of many SARS-CoV-2 variants, with the mid part of the year seeing an increase in their spread, leading to the second, and at many places a third, wave of infection escalation. Although the past decade had started to prime the health care systems of the need and use of genomics in health care, however, the need for genomic surveillance during the pandemic provided an unexpected thrust and brought this to the forefront, as it is now a defining strategy for tracking and containing the virus.
In the year past, nearly 3,60,000 SARS-CoV-2 variants had been sequenced and stored in GISAID, a non-profit online database for sharing viral genomes. UK’s COVID-19 Genomics Consortium (COG-UK) has also propelled its efforts in sequencing the viral genomes. These efforts helped in identifying the B.1.1.7 variant in UK, leading to travel restrictions and policy interventions. In India, the Indian SARS-CoV-2 Genomic Consortium (INSACOG) is funneling genome sequences from 10 network labs for public health decisions. Genome sequencing, despite gaining importance during this pandemic, because of the lack of enough sequencing initiatives and the slow rate of sequencing in INSACOG due to hiccups attributed to resource and logistics, was being considered ‘potentially disastrous’ at a time when these variants (UK strains, South African strain and Brazilian strain) were reportedly on an upswing in the Indian population, with many states re-imposing partial curfews and lockdowns. For the period January-March 2021, only one per cent (7,664 samples) of the total positive samples was sequenced, as opposed to the target of five per cent. April saw the emergence of the second wave in India, the outcomes of which were unprecedented!
The emergent Delta strain that is presently circulating is one of four ‘variants of concern’ identified by the World Health Organization, along with four ‘variants of interest’. It is quite different from the virus that appeared in Wuhan, China, in late 2019. Due to this unexpected turn, countries around the world are still grappling with pandemic planning and containment!
Researchers, doctors and evolutionary biologists were baffled with the rapid evolution of the virus in a short timeframe, while they had only the previous experience of working on bacteria and viruses that have been in existence for decades or centuries. Not only did this virus escape the immune system, but a study in Scotland also showed that the Delta variant was about twice as likely to lead to hospital admission vis-à-vis the Alpha, highlighting how quickly it got evolved and adapted to continue its spread!
As of mid-September, 40 per cent of the world population had received at least one dose of the vaccine, out of which only two per cent were from LMICs! Till vaccine equity is achieved and future pandemic preparedness measures are put in place, it becomes imperative to keep a close watch on the virus itself. Genomic surveillance is an important and cost-effective way of achieving this.
Going further
Overall, the last two decades, and now the tipping point unexpectedly provided by the pandemic, has generated enough reasons for us to accelerate genome-based discoveries and surveillance in humans as well as in the microbial world, as these analyses of genomic studies can provide a ‘genetic cautionary’ note for the management of these diseases and our future preparedness, both at individual as well as the population level.
The article is last of three parts of a larger article published in the September-October 2021 issue of Invention Intelligence, a magazine published by the National Research Development Corporation (NRDC), A DSIR Enterprise, Ministry of Science & Technology, Government of India.
Also read Part-1 (Race to the Genomes)and Part-2 (Being Precise: Genomic Medicine)
