Advocating Asian-Centric Precision Diagnostics

Multi-modal AI for Digital Health - Introduction
From data to precise solutions: Data-powered medicine and therapeutics

Precision Medicine 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 Asian-centric 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. A*STAR is at the forefront of cutting-edge R&D activities driving new insights into disease mechanisms and regulatory biology, and data generated by large-scale PM initiatives for precision diagnostics.

 

Multi-Omics Profiling

Our approach begins with the integration of diverse multi-omics data:


  1. DNA/RNA Profiling: Comprehensive sequencing and analysis of genetic material to uncover crucial insights into disease mechanisms.
  2. Protein/Single-Cell Profiling: Detailed examination of protein expression and cellular heterogeneity, providing a deeper understanding of cellular functions and interactions.
  3. Functional 2D/3D Systems: Utilizing advanced modeling systems to simulate and study complex biological processes in a controlled environment.

 

Data Storage & Processing

The vast amount of multi-omics data generated is stored and processed using sophisticated bioinformatics infrastructure:

  • AI and Simulation: Employing artificial intelligence and simulation techniques to analyze data, predict outcomes, and generate actionable insights.
  • Multi-Omics Database and Repository: Centralized databases that facilitate efficient data access, interrogation, and integration across various research projects.

Multi-Modal and Longitudinal Patient Datasets

Singapore's government has seeded numerous R&D initiatives aimed at advancing precision medicine through the integration of multi-modal and longitudinal patient datasets. The following are some data assets generated in collaboration with A*STAR. A*STAR also possess it's own Biomedical Data Access Repository (Biomed-DAR), a data play space for long-term hosting and value creation of programmatic research data from multiple health clusters and National platforms.

Data AssetKey Descriptors
PRECISE
(Population Health)
  • World's 1st multi-ethnic Asian genetic database
  • Rare disease discovery + Asian variants
  • Genomic, phenotypic, lifestyle and clinical
CALIBre
(Oncology)
  • Longitudinal cell-free liquid biopsy & multi-modal profiling of cancer
WCIT & ASMP
(Chronic Wounds/Skin Microbiome)
  • World’s first Asian chronic wound repository (n=800) to advance dressings, diagnostics, and treatments
  • Asian skin microbiome (n=2000) for metagenomics, metabolomics, lipidomics across ethnicity, age, skin health and physiology
EMULSION
(Liver Disease)
  • Asian-centric NAFLD clinical & multi-omics database
  • Patient-derived bio-resource of renewable primary liver stem cells – liver on a chip
  • In vivo mouse models
GUSTO-DevOS (Mother-Baby)
  • Pregnancy ➔ infancy ➔ adulthood
  • How pregnancy & early childhood influence the health and development of women and their children (n=1200 pairs)
ATTRACT
(Heart Failure)
  • ASIAN-HF study which involves about 50 sites in 11 countries echo, ECG and DNA with tracking of longitudinal outcomes (n=3000 ➔ 8000)
  • Develop large animal model of HFpEF
APOLLO
(Coronary Vessel Disease)
  • CT Coronary Angiography scans (n=5000) precision toolkit for anonymization, Agatston scoring, and plaque quantification

Case Studies

Oncology Research & Applications in Precision Medicine

Singapore is making significant strides in oncology research and applications within the realm of precision medicine. Through strategic partnerships and innovative spin-offs, A*STAR is at the forefront of developing cutting-edge diagnostics and therapeutics to combat cancer more effectively.

Here are two key initiatives driving this progress:

BC Platforms working with A*STAR's Biomed DAR and Privacy Preserving to increase fidelity of research data for multi-party computing

In a landmark collaboration, A*STAR - Agency for Science, Technology, and Research, and BC Platforms have launched a joint lab aimed at advancing secure biomedical data informatics. This partnership is a significant milestone in enhancing the fidelity of research data for multi-party computing, fostering innovations with real-world applications, and ultimately improving patient outcomes.

 

A*STAR and BC Platforms

Secure Biomedical Data Informatics with BC Platforms and A*STAR (Source - LinkedIn)

 

National Precision Medicine Programme
National Precision Medicine Programme

Singapore’s National Precision Medicine Programme is a whole-of-government effort to drive precision health research, improve patient outcomes, and capture economic value.

A*STAR’s wide-ranging and multidisciplinary scientific expertise has contributed greatly to this programme. These include developing polygenic risk scores and genomic imputation services which are made available in the NPM web portal: extraction, sequencing, data QC and primary to secondary processing and development of reference panel; and tertiary level analysis such as protein modelling work.

New Multi-Omics Detection Platforms for Precision Medicine Through A*STAR Spinoffs

A*STAR has nurtured several innovative spin-offs focused on advancing cancer diagnostics. Notable among these are:

MiRXES - Early Detection of Gastric Cancer

MiRXES Spin-off
A*STAR Spinoff - MiRXES
MiRXES specialises in the early detection of gastric cancer using miRNA technology, enabling personalized cancer treatment selection. Their solutions are designed to detect cancer at its earliest stages, significantly improving treatment success rates.

Lucence - Early Detection of Various Cancers

Lucence focuses on the early detection of various cancers, including solid tumours and haematological malignancies. Their technologies identify genomic alterations such as single nucleotide variants, insertions, deletions, copy number variations, and microsatellite instability, providing comprehensive insights into cancer genetics.
A*STAR Spinoff - Lucence
A*STAR Spinoff - Lucence

End-to-End Diagnostics Systems with Integrated Workflow

A*STAR is committed to enhancing clinical diagnostic workflows through a comprehensive, end-to-end approach. This methodology ensures quality execution and holistic capabilities from sample collection to output, integrating advanced technologies at every stage.

End-to-end Integrated Dx Systems and Workflow
End-to-end Integrated Dx Systems and Workflow

Sample Collection & Preparation

  • Saliva/Deep throat collection & inactivation
  • 3DP nasal swab
  • Faeces processing
  • Nucleic acid extraction
  • Rare cell sorting
  • Oocyte processing for IVF

Reagents/Antibodies

  • mAb Development
  • T cell/B cell
  • Antigen & nAb
  • Epitopes
  • Lyophilization
  • Modular PCR assay mix

Assay/Chip Development

  • LAMP/PCR
  • miRNA
  • Epigenetics
  • Lateral Flow
  • Impedance Sensors
  • Microfluidics

Lab Instruments And Automation

  • Applied AI Robotics & Automation
  • Adaptive mechanisms & actuators
  • Liquid handlers/molecular profiling stations/flow cytometers
  • Biophotonics, multi-spectral imaging

Software Analytics & Output

  • qPCR analytics
  • Bioinformatics
  • AI analytics
  • Data interpretation & readout

Microfluidics Foundry: ISO13485

A*STAR houses the ISO13485 Microfluidics Foundry which innovates in polymer microfluidics manufacturing to create value from emerging applications for rapid sample processing, molecular diagnostics, and biological sample analysis. The foundry possesses capabilities for customized plastic chip moulding, bonding, assembly and testing and houses a microfabrication line with robust processes to ensure unparalleled quality and value.

Process Technology
Process Technology
  • Mould Fabrication & Structuring
  • Secondary high throughput bonding & surface modification
  • Monitoring control & automation
Microfluidics Application
Microfluidics Application
  • Design and Simulation
  • Flow manipulation 
  • Sensor development and integration

COVID-19 Case Study

Improving End-to-End PCR Test Workflow

In response to the COVID-19 pandemic, A*STAR has developed a streamlined end-to-end PCR test workflow to enhance efficiency, accuracy, and safety in diagnostic testing.

COVID-19 Case Study: Improving End-to-end PCR Test Workflow
End-to-end PCR Test Workflow

Key Components

  • RESOLUTE Series:
    The strategic partnership between DSO and A*STAR resulted in the co-development of the direct PCR SARSCoV-2 detection kits RESOLUTE 1.0, and subsequently, RESOLUTE 2.0, which have proved pivotal in the early COVID-19 pandemic response. RESOLUTE 2.0 does not require the need for extraction of viral RNA from patient test samples. This minimises potential human errors and halves the test delivery time.
  • RAVE/BRAVE+:
    Lab automation and liquid handlers designed to process samples with minimal manual intervention. These systems automate critical steps such as uncap & cap, barcode reading, and sample transfer to deep well plates and secondary tubes.
  • INSPECTA:
    INSPECTA uses a Machine Learning algorithm to reduce the time required to interpret quantitative polymerase chain reaction (qPCR) results in high volume laboratory workflows.

Workflow Stages

  • Sample Inactivation:
    Safely inactivating the virus in collected samples to ensure safe handling.
  • Barcode Read:
    Scanning barcodes for sample identification and tracking.
  • Uncap & Cap:
    Automated uncap and cap of sample containers to prepare for processing.
  • Deep Well Plate Processing:
    Transferring samples into 96 deep well plates for high-throughput processing.
  • PCR Analysis:
    Extracting RNA and performing PCR analysis to detect the presence of SARS-CoV-2.

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