Precision Medicine And Population Genomics

Precision Medicine (PM) is an emerging approach where individual and group variability in genes, environment, and lifestyle are integrated to predict disease risk, diagnose disease, tailor therapies, and reduce clinical complications. By analysing population-scale genomic, clinical, and lifestyle data, targeted strategies can be developed for specific individuals and groups to improve outcomes and maximise health span while mitigating healthcare costs. PM is an enabler of cutting-edge R&D activities driving new insights into disease mechanisms and regulatory biology, and data generated by large-scale PM initiatives represent valuable use-cases for next-generation data platforms including privacy preservation analytics, multi-party computation, and artificial intelligence (AI). PM also provides opportunities for capturing economic value by enhancing the biomedical science sector with genomics/PM-related companies, and companies in related industries including biopharmaceutical and medical technology, consumer, data, and process innovation.

Reflecting the global interest in PM, many countries have embarked on national-scale PM initiatives and many of these are in various stages of development and implementation. With 4 billion inhabitants, Asia is home to the largest population aggregation in the world. However, in contrast to European efforts, there is a current lack of large-scale control databases comprising Asian-specific genetic variation that is linked to clinical phenotypes. This is a major barrier to the conduct of PM in Asia, as such databases are essential to avoid misdiagnosis and overtreatment due to the mistaken identification of pathogenic variants. With the significant presence of three major Asian ethnic groups (Chinese, Indians and Malays), there is thus a unique opportunity for Singapore, despite its small size, to contribute to global efforts in PM, complementing other large-scale efforts. Insights gained from Singapore may also result in products and services that can be applied to health systems in larger Asian countries.

Singapore also has additional strengths that make the nation competitive in PM. These include strong institutional capabilities in genomics, engineering and analytics. It also uses a unique national identifier (NRIC), which facilitates integration of healthcare and research datasets across different public healthcare systems. These strengths can be readily leveraged to implement PM and build the nation’s reputation as a trusted location for data security and standards. Singapore has an advanced healthcare system with highly-trained, globally-experienced clinicians that will allow the adoption of innovations. It also has a rich 20-year ecosystem of biomedical research and national platforms for extending initial discoveries made by PM into drug compounds and diagnostic assays.

Since its founding in 2000, PM and population genomics has been a core disease focus of GIS, as exemplified by its several genetics labs within GIS and associated external labs. The key strengths are:

  • Human genetics: GIS has had a strong track-record of publications describing the genetic architecture of various disease traits, with a particular focus on conditions of Asian prevalence. These include the identification of genetic variants associated with severe drug reactions, genes related to eye and other neurological conditions, and immunological diseases. The institute is also involved in several large-scale international human genetics consortia, such as the global partnerships investigating type 2 diabetes, chronic kidney disease, and breast cancer. GIS is also the home base for the Asian consortium for Parkinson disease, Schizophrenia, as well as glaucoma.
  • Precision oncology: Oncology has represented a major focus area of PM. GIS has many strengths in the oncology space, including identification of genetic variants linked to cancer susceptibility, expertise in the biological understanding of several Asian-endemic cancers including lung, liver, and gastric cancers, and leadership in national consortia for clinically annotated longitudinal profiling of cancer patients (liquid biopsies). GIS also has experience in “n-of-1” studies where cancer patient responses are modelled using organoid platforms.
  • Rare genetic disease and clinical diagnostics: Working closely with clinical partners, GIS has participated in the use of genomic sequencing to accelerate the diagnosis of children with rare, undiagnosed genetic diseases. To date, >100 children have been successfully diagnosed through such efforts. GIS, through its POLARIS programme, has also contributed towards translating these genomic sequencing assays into clinical-grade diagnostic applications for mainstream healthcare implementation.
  • Asian population genomics: GIS has spearheaded the creation of the largest collection of Asian whole-genome sequencing data, comprising the three major Singapore ethnic groups. Comprising close to 5000 individuals, comparison of this Singapore database to Western population databases revealed the presence of millions of novel genetic variants. Availability of these reference databases forms a foundation for Asian PM.

Related links:
Centre for Genome Diagnostics
Eye Genetics