NEW YORK – The Council of Scientific and Industrial Research in India recently announced the whole-genome sequencing of a thousand individuals from different populations.
The project, called IndiGen, aims to better understand genetic diversity around the South Asian country, while helping to inform clinical applications. Following the completion of its pilot phase, its next plan is to scale the program to 20,000 genomes, according to Sridhar Sivasubbu, a principal scientist at the CSIR Institute of Genomics and Integrative Biology in New Delhi.
"We have plans for scaling up the genome sequencing activities under IndiGen for biomedical applications," Sivasubbu said.
CSIR, the largest R&D organization in India, initiated the IndiGen project in April this year. The effort has been carried out by CSIR-IGIB in New Delhi and the CSIR Center for Cellular and Molecular Biology in Hyderabad. Sivasubbu said that one of the major driving factors behind the IndiGen project has been to ensure that India, given its human diversity, is well-represented in terms of genomic data. He did not provide a specific budget for the effort, but CSIR is funding the project through a research grant.
By supporting the whole-genome sequencing of individuals, CSIR aims to develop an "indigenous capacity" within India to generate, maintain, analyze, utilize and communicate large-scale genome data in a scalable manner, Sivasubbu maintained.
"Furthermore, we wanted to benchmark the scalability of genome sequencing and computational analysis at population scale in a defined timeline," he said of the recent pilot phase. CSIR set out to achieve this benchmarking within the first six months of the project, and both CSIR-IGIB and CSIR-CCMB used the Illumina NovaSeq6000 sequencing system to generate the results, he said.
By the end of September, the organization had completed the whole-genome sequencing of 1,008 individuals. Sivasubbu said that the sequencing of this first batch of individuals has just been completed and the researchers will have insights shortly. While the work is valuable in terms of better comprehending the genetic variability in India, which has 23 official languages and a population of 1.3 billion people, CSIR aims to transition its efforts into clinical applications. This includes not only untangling the genetic epidemiology of diseases, but supporting the development of technologies that enable new clinical and biomedical applications in India, and pharmacogenomics is on the list.
One application is the IndiGenome card which together with an accompanying IndiGen mobile application enables participants and clinicians to access clinically actionable information from their genomes, such as pharmacogenomics data. According to Sivasubbu, the card has been designed with privacy, data security, and scalability in mind, which he said is "vital for personal genomics to be implemented at a population scale."
He said the IndiGen card is currently being pilot tested in individuals across India, and has "evinced interest from several Indian commercial organizations." It is reminiscent of a European project led by investigators at the Medical University of Vienna to introduce safety code cards to patients that can provide pharmacogenomic data to physicians making treatment decisions.
Even at this early stage, IndiGen has numerous commercial partners. These include Dr LalPath Labs, a chain of Indian diagnostic laboratories; Chennai-based LifeCell International, which offers a next-generation sequencing-based test called Genomescope for critically ill newborns; Mahajan Imaging, a New Delhi-based imaging and diagnostics center; Bangalore-based Premas Lifesciences; Indus Health Plus, a healthcare company headquartered in Pune; and even TagTaste, a new food and technology company based in Noida, outside New Delhi. Most IndiGen partners intend to use the findings of the project to improve the accuracy of their tests.
Another such partner is Genique Lifesciences, a genomics healthcare company based in Gurugram, on the outskirts of New Delhi, which offers carrier screening, ancestry, newborn screening, and health and wellness testing services. CEO Abishkek Das said that Genique has partnered with CSIR-IGIB to develop a reporting engine for genetic diseases and has used the India-specific data from IndiGen to "fine tune" its reporting engine for carrier screening.
"Our collaboration has helped us to develop a cost-effective, India-centric Carrier Screening Panel that can be used by at-risk couples to make an informed choice," said Das. "From a diagnostic perspective, it adds Indian population-specific reference data that can be used to make a more accurate genetic risk assessment of patients undergoing testing," he said.
According to Das, Genique is currently validating the test and expects to launch it later this month. The company has also developed a diabetic and cardiac screening panel but requires more data to launch it, he said.
"By our estimates, the potential market size for these tests in India initially would be around 100,000 samples per annum and will then grow from there as awareness increases," Das noted.
According to Das, most existing datasets for Indian populations are concentrated in certain regions or populations, such as Gujarati, an ethnic group in western India, or Tamil, an ethnic group in southern India and Sri Lanka.
"IndiGen provides us with a more diverse and geographically representative Indian data set to refer to," said Das. "This means our inferences are better informed by the data set and hence more accurate."
Vid Karmarkar, head of genomics at Indus Health Plus, called IndiGen a "major milestone" in the Indian genomics space, as it will generate human genome data from Indian ethnicity that is currently under-represented in the genomic databases.
"Lack of Indian genomic data is a major bottleneck for basic and applied research in genomics and genetic epidemiology," said Karmarkar. "This is a major hurdle in developing products and applications of utility to Indians," he said. Karmarkar said that genomic products informed by IndiGen data will "take Indian preventive healthcare to the next level."
Indus Health Plus, he noted, focuses on early disease detection and preventive healthcare. Among the company's offerings is DNAWise, a personalized genetic testing package that includes 60 health reports. Indus Health Plus launched the saliva-based test a year ago. The test is run using Illumina genotyping arrays. In addition to providing data on nutrition, health, and wellness, Indus Health Plus also offers genetic counseling related to the offering.
"We see the immense utility of Indigen data to develop personal genomics products and offer next-generation preventive healthcare that will use biochemical and genomic approaches," commented Karmarkar. "Such approaches will be critical to reduce the burden of lifestyle associated non-communicable diseases, which is one of the leading causes of deaths in India."
The Indian experience
While IndiGen commenced earlier this year, its roots are in Sivasubbu's work in the lab of Vinod Scaria at CSIR-IGIB. He said they commenced whole-genome sequencing of individuals there in 2009 and also have sequenced individuals for partners in Malaysia and Sri Lanka.
In addition to IndiGen, the investigators are involved in another effort called the Genomics for Understanding Rare Disease: India Alliance Network (GUARDIAN), a "precision medicine ecosystem" focused on rare genetic diseases. The consortium involves roughly 280 clinicians and researchers from about 70 medical and research centers around the country.
Within the framework of the consortium, clinicians can refer patients with rare genetic diseases for whole-genome or -exome sequencing to identify the causal pathogenic variations. Findings from the consortium are then distributed among members and used to design low-cost diagnostic assays in India. The researchers discussed the network in a September paper in Human Genetics.