CHICAGO – SG100K, a study to sequence and analyze the genomes of 100,000 Singaporeans, has moved into a new phase combining phenotyping and genotyping, courtesy of a partnership between Nanyang Technological University (NTU Singapore) and bioinformatics vendor BC Platforms.
The study, called Health for Life in Singapore, or HELIOS, is a population cohort study focusing on environmental, lifestyle, and genetic factors that cause chronic diseases such as diabetes, cancer, Alzheimer's disease, Parkinson's disease, and heart disease in Singapore. It aims to recruit up to 50,000 people of Chinese, Malay, and Indian ethnicity between the ages of 30 and 84 over the next two years, or half the total SG100K cohort, for additional phenotyping.
The Lee Kong Chian School of Medicine at NTU Singapore is leading HELIOS in collaboration with Singapore's National Healthcare Group and Imperial College London. The common thread between NTU Singapore and Imperial College London is SG100K principal investigator John Chambers, who holds a joint faculty appointment at both schools.
Chambers called SG100K "a federation of cohorts," including HELIOS and two "legacy" projects, namely the School of Public Health Studies and a program called Singapore Epidemiology of Eye Diseases, or SEED, run by the Singapore Eye Research Institute.
The two older cohorts, which date to the late 2000s, were helpful for biomarker discovery for incident disease, according to Chambers. "The main downside has been that they're quite light on the baseline phenotyping," he said.
Through genotyping and phenotyping of a mostly Asian population, HELIOS is attempting to address what Chambers called an "imbalance" of precision medicine that is biased toward white populations.
"We saw that Europe and North America were making great advances in population health through well-conducted cohort studies with comprehensive phenotyping," Chambers said. "Our vision was to bring those kind of approaches to the Asia-Pacific region to accelerate our understanding of precision and population health."
Chambers called this a clear health disparity. "Fundamental in epidemiology is that it's also a window of opportunity for discovery. If you want to find out new things about disease mechanisms, a really good place to start is to go to a group of people who've got the disease," he added.
Chambers, a UK native, noted the multiethnicity of his home country. "I could see there were tremendous differences in health and health outcomes between non-European and European populations," he said.
Notably, people of Asian heritage had high incidence of early-onset cardiovascular and metabolic diseases.
"There's all this research being done into how to treat European folks and nobody has any understanding what genetic or environmental factors were driving disease in Asians," Chambers said, estimating that Asia was two decades behind Europe in this regard.
Chambers called HELIOS one of two major large-scale population cohorts in the Asia-Pacific region, along with the South Asia Biobank study on the Indian subcontinent that also involves Imperial College London.
The entire SG100K program is funded by a grant administered by the Singapore Ministry of Health's National Medical Research Council and supported by the National Research Foundation Singapore. By involving research, clinical, and commercial partners, the project will be able to monitor long-term health outcomes of participants in order to yield insights into Asian genomic diversity and Asian-specific diseases.
The latest commercial partner, announced last month, is BC Platforms, which is providing the technological framework for data collection and interoperability in the HELIOS study.
The Zurich, Switzerland-based bioinformatics software company is supplying its BC|Insight open discovery and analytics platform and BC|Rquest global biobank analytics platform to manage the Chian School of Medicine's genotype and phenotype data from the HELIOS cohort.
Nino da Silva, deputy managing director of BC Platforms, called data fundamental to any population health program. "But once you have the data, you need to be able to share it," and do so in a way that everyone involved can understand and trust.
"An underused cohort is a failure," da Silva said. "The prime mission that we have now … is to help build the network around this data."
As new records come in from HELIOS enrollees, BC Platforms curates and normalizes the data based on the Observational Medical Outcomes Partnership (OMOP) Common Data Model so researchers have an easy means of comparison.
BC|Insight version 7, introduced in November, provides secure virtual workspaces for authorized researchers to query data.
Users never download the data off BC Platforms' servers. "They just look at it," da Silva said. "If they find the cohort that they want … they can then apply for research on that cohort," and the HELIOS team acts on that request, granting or denying access.
The BC Platforms involvement in HELIOS follows that of metabolomics firm Metabolon, which in September announced a partnership with the Chian School of Medicine for the identification of biomarkers for a range of health conditions. Metabolon will access data from an NTU Singapore-led population cohort study to identify biomarkers related to the prevention, diagnosis, and treatment of a range of conditions.
Illumina and Precision Health Research Singapore (PRECISE) last year formed a strategic partnership to sequence and analyze the genomes of SG100K participants. Chambers also serves as CSO of PRECISE, a business unit of the Consortium for Clinical Research and Innovation, Singapore (CRIS), a subsidiary of the Ministry of Health Holdings, which develops national clinical research and translation programs on behalf of the Ministry of Health.
NTU Singapore has a custom in-house platform for data collection, but BC Platforms is the sole vendor for data management within the HELIOS cohort, connecting researchers with the information they need.
When it updated BC|Insight a few months ago, BC Platforms also introduced a secure cloud computing feature called the Trusted Collaboration Environment (TCE) that provides open workspaces for drug discovery based on the principle of trusted research environments, or TREs.
Da Silva said that HELIOS is initially adopting the TRE strategy because there is a single data custodian, NTU Singapore. Chambers said that it is his "vision" for the university to belong to a wider collaboration environment in the future.
"We spent years building up the foundations to enable the research," in the form of a research cohort like HELIOS, Chambers said. "Then you put it in the right industrial partnerships so you can generate the whole-genome sequence data or other sequencing data," which for HELIOS is Illumina.
BC Platforms is addressing the next requirement, providing a bioinformatics platform to make the data accessible. "We're now just about to go into the science production," Chambers said, meaning answering questions about the high prevalence of diabetes in Asian populations.
Chambers said that HELIOS necessarily must be a multiomic and multimodal study.
"Is it genetic? Is it environmental? Is it behavior? We now, for the first time, have got those three components of data characterized properly so we can understand … whether there are multiplicative or additive effects between different genetic environments," Chambers explained.
He added that there are "no decent datasets" to determine whether Asians are more or less physically active than Europeans. Previous questionnaires have not been reliable or unbiased enough for Chambers' liking.
"For the first time, we've got large-scale quantification of diet. For the first time, we've got geolocations for individuals, hundreds of thousands of individuals, so we can overlay environmental data such as heat stress, environmental pollution, and other environmental exposures … that may impact people's health and well-being," Chambers said of HELIOS.
The sequencing data then allows researchers to pinpoint genetic variants that are shared and those that are specific to certain populations.
"There are major undiscovered risk factors or biological mechanisms that are waiting to be detailed," Chambers said. "When I [started], I thought [it] was going to be genetic, but it's proven not to be purely genetic."
Chambers called it "dead easy to engineer simple cross-sectional genetic associations, a bunch of cases and a bunch of controls. But that didn't solve the problem, so we've had to move into the longitudinal population, which requires the cross-factor evaluation of behaviors, environmental exposures, and molecular disturbances."
Da Silva said that the HELIOS work will also create "massive potential for pharmaceutical companies" to target drugs to Asian markets, and possibly worldwide.
To this point, Chambers noted that PCSK9 was discovered in an African family, leading to the development of new drugs for fighting familial hypercholesterolemia worldwide. "We do believe that [our] research has the prospect to make discoveries that are critical for Asian populations, but will be of global relevance," he said.
Da Silva said that BC Platforms has seen the number of requests from pharma clients for multi-haplotypic data, including Asian cohorts, triple in the last two years.
BC Platforms and NTU Singapore have been running several "test projects" for HELIOS over for the past year and a half, according to da Silva. The partners have not yet reported any results from those pilots.