Why this team is trying to sequence 100,000 Asian genomes

Key Concepts

• Genomic diversity
• Ethnic minorities in genomic studies
• GenomeAsia 100K project
• Genetic markers (ethnic vs. disease)
• Next-generation sequencing
• Precision medicine
• Disease alleles vs. ethnic alleles

1. Introduction: Addressing the Diversity Gap in Genomic Studies

• Genomic studies have historically focused on individuals of European ancestry, neglecting ethnic minorities.
• The GenomeAsia 100K project was established in 2016 by MedGenome and Nanyang Technological University (NTU) in Singapore to address this gap.
• The project aims to sequence 100,000 genomes to create a comprehensive genetic representation of Asian human variation.

2. GenomeAsia 100K Project: Goals and Objectives

• The project has two primary goals:
  • Understand the genetic makeup of Asians as a whole.
  • Identify genetic markers specific to Asian populations and differentiate them from disease markers previously identified in European populations.
• Stephan Schuster, the Scientific Director of the project, emphasizes the importance of distinguishing between ethnic markers and disease markers.

3. Sample Collection and Sources

• The project builds upon the work of previous generations of scientists, particularly Japanese anthropologists who collected samples over decades.
• These existing samples were converted into digital information to prevent degradation and serve as building blocks for the project.
• The project also relies on contributions from national collections, donors, clinicians, and scientists.

4. Laboratory Processes: DNA Extraction, Library Construction, and Sequencing

• Sampling and data analysis are conducted in two labs at NTU.
• Scientists extract DNA from human tissue and prepare it chemically through a process called library construction, which is achieved with the use of robotics.
• Prepared DNA is loaded into a sequencer that translates the data into digital information.
• Each sequencing round takes approximately three days, and the machine can produce around 80 human genomes per week.

5. Technology and Data Analysis

• Hie Lim Kim, the project’s lead researcher, highlights the cutting-edge technology used:
  • Speed of DNA sequencing.
  • Ability to process large amounts of data simultaneously.
  • Use of significant computing resources.
• Robotics and automation are crucial for handling the large-scale data.
• Artificial intelligence (AI) is used to identify genetic variations and annotate their functions.

6. Project Progress and Key Insights

• As of the time of the interview, the project had sequenced around 10,000 genomes from 25,000 samples, spanning 450 Asian ethnicities.
• Key insights gained:
  • The genetic diversity of Asians is greater than initially expected.
  • It is crucial to collect, describe, and work with indigenous groups, whose contributions are vital and who are at risk of extinction.

7. Medical Relevance and Precision Medicine

• The project aims to differentiate between disease alleles (genetic variations contributing to medical conditions) and ethnic alleles.
• This data can help scientists understand the susceptibility of specific communities to particular diseases.
• Next-generation sequencing enables personalized medicine by allowing the sequencing of a patient's genome to tailor treatments and medications.
• The project emphasizes that precision medicine requires precise knowledge of an individual's genetic background, which includes ethnicity.

8. Pharmaceutical Development and Ethnicity

• The current pharmaceutical development model is likened to producing only one size and color of t-shirt (white, XL) for everyone.
• The pharmaceutical industry needs to consider ethnicity when developing drugs to ensure compatibility and effectiveness across diverse populations.
• Ethnicity is currently underrepresented in precision medicine.

9. Conclusion: The Importance of Diversity in Genomic Research

• Diversity in genomic research is essential for ensuring that medicine works for all populations.
• Expanding data sets unlocks the stories of the past and increases medical opportunities for future generations.
• The GenomeAsia 100K project contributes to a more inclusive and equitable approach to healthcare by addressing the historical neglect of ethnic minorities in genomic studies.