As the captain of the National Precision Medicine programme, Dr. Claire Bellis from A*STAR’s Genome Institute of Singapore is ensuring that the programme functions like a well-oiled machine and is helping Singaporeans live healthier lives.
Launched in 2017, Singapore’s National Precision Medicine (NPM) programme aims to provide a near-complete assessment of the common genetic variants in Singapore’s major ethnic groups. Achieving this mammoth task requires consistent collaboration across the academic medical community, healthcare community, public research institutes, and private companies to develop the necessary infrastructure and capabilities that would support the collection, storage and processing of genetic data for disease studies.
The intricacies of this endeavour can be likened to the operation of a sophisticated machine, where stakeholders play different parts to ensure its functionality. Realising the complexity of this process, Professor Patrick Tan, Executive Director of Precision Health Research, Singapore (PRECISE) and GIS, enlisted the help of talents from a myriad of institutes within A*STAR, including Dr. Claire Bellis from GIS, clinicians and researchers located at major hospitals and universities in Singapore who literally have their fingers on the pulse of the health of Singapore. “If we were to imagine the entire programme as an engine or machine, I would consider my role the oil for all the moving cogs; ensuring programme objectives, deliverables, deadlines, key-stakeholders, etc., are all aligned, running as smoothly as possible”, Dr. Bellis says. In her work so far, Dr. Bellis made sure the programme didn’t miss out on tapping on the best and brightest of Singapore’s knowledge assets in precision medicine.
Singapore’s NPM approach is based on best global practices and includes three strategic phases: Proof of Concept ( which aims to sequence 10,000 healthy individuals), Proof of Value ( a long-term study to collect genomic data from 100,000 individuals), and Proof of Scale (a mission to sequence up to one million genomes). Together, they will result in embedding genetics in clinics, generation of Asian-specific disease risk modelsand catalysing local genomics industries through local startups. “When we started with Phase 1 of SG10K implementation, various learning opportunities were identified through pain point analyses”, she shares. “One such bottleneck we identified was associated with the supply of DNA samples to “feed” the sequencing instruments”. This learning opportunity paved the way for the establishment of the nEXT geneRation Automated Centre for high-throughput sample processing and roboTics laboratory, or simply EXTRACT. EXTRACT uses next-generation robotics to enable large-scale DNA extraction capability and bridge the resource gap in institutions that also need to recruit participants and perform sample phenotyping as part of SG100K. The establishment of this onsite lab freed up resources that could be diverted into non-repetitive tasks in line with the future phases of the programme. Employing robotics also reduces possible human errors in processing samples.
The foundation has been laid, and the machine buzzes as collaborators pitch their initiatives. But what is next for Singapore’s NPM programme? When a team from the Telomere-2-Telomere (T2T) Consortium mapped the missing ~8% of the human genome and completed the book of life’s missing chapters, scientists globally were promised access to a complete reference genome to further genomic research. Although this reference genome is based on approximately 3,000 individuals from diverse ancestries, it is imperative to generate a local Singaporean reference where unique variations and patterns in the genome may give rise to more confident conclusions on matters impacting public health.
“The last decade has witnessed the most aggressive advancements in genome sequencing. This is great news for precision medicine programmes aiming to sequence at the population scale”, she adds. Precision medicine has been shown, for a variety of conditions, to predict the onset of disease before the healthy individual presents to the clinic with symptoms. Further, the success of Singapore’s NPM will allow local physicians access to the SG100K database to understand the frequency of certain genome variations in the population and whether, for example, any known adverse drug responses have been detected, before prescribing a particular medication. “Prevention is better than cure, after all. As such, NPM aims to sequence 100,000 genomes.”, Dr. Bellis quips.
Given that the first successful attempt at sequencing the human genome in 2001 cost a staggering USD$1,000,000,000, one may wonder how a population approach to this framework can be realised. “The answer is technology disruptors”, Dr. Bellis notes. The recent years saw a significant reduction in sequencing costs due to lowered computing power costs. The idea of a US$100 genome has even been put on the table by startup Ultima Genomics. Cost reduction, complemented by technological advancements using long-read sequencing approaches, is making every country’s national precision medicine agenda closer to reality. “Using a long-read sequencing technique, the fastest sequence of a human genome record was set. At only 5 hours and 2 minutes, this feat elicited tremendous excitement throughout the precision medicine, health and diagnostics fields”, she shares. “This advancement truly delivers on the promise of genome sequencing integration into routine medicine.”
Aside from reviewing and evaluating pre-print manuscripts for potential novel studies that may be adopted in the local context, Dr. Bellis capitalises on longstanding relationships with institutions that harbour the same goal. “I have been lucky enough to foster working relationships with groups such as the All of Us Research Program in the United States, Genomics England, and Karolinska Institute Biobank, each of which has truly assisted with knowledge transfer associated with GIS’ EXTRACT Lab”, she notes. Dr. Bellis believes that there is a strong justification to develop a similar collaborative ecosystem in Singapore. “For precision medicine to assist Singaporeans with their health and medical requirements, we need access to genomes of our local population.” This is what NPM hopes to achieve – to not only create the necessary infrastructure, but also train local talent and extend them access to the rare resource.
Ensuring the NPM’s complex and highly-collaborative system functions smoothly, like a well-oiled machine, is anything but simple. It comes with potential roadblocks and uphill slopes that the NPM, through Dr. Bellis navigates. “The uniqueness of one’s genome sequence can be likened to a biological footprint or a digital twin. It is also a window that peeks into a person’s possible health scenarios, hence, trust between researchers and study participants will need to be nurtured by engaging the public”, she says.
The good thing is Singapore has government-mandated governance and policies in place to cover health data sharing and privacy preservation concerns.
Dr. Bellis hopes that in the future NPM will reach a stage of maturity where the genome and clinical data of over one million Singaporeans, possibly the entire population is analysed. “When realised, this opens up tremendous potential for clinicians and researchers alike to generate patient-specific diagnoses for a range of diseases, earlier and with greater confidence”, she envisions.