The Ancestry and Health Genomics Lab is defining the extent and complexities of human and cancer genome diversity.
Our researchers use this multi-omic variance to trace human ancestry and global health disparities, in particular prostate cancer.
“There comes a point where we need to stop just pulling people out of the river. We need to go upstream and find out why they are falling in.”
- Archbishop Emeritis Desmond Tutu (1931-2021)
In fond memory of our greatest advocate – Archbishop Emeritis Desmond Tutu. We thank him for his belief in our work, and his significant contribution to enabling African inclusion in the genomic revolution and the benefits of precision medicine for improved prostate cancer outcomes for African men.
Prostate cancer (PCa) is characterised by significant geographic and ancestral disparity. While incidence rates are highest in Australia, mortality rates are highest in Sub-Saharan Africa, with both incidence and mortality lowest across Asian nations.
In turn, PCa associated death is greatest for men of African followed by Asian ancestry and lowest for European ancestral men. This significant health disparity, suggesting both genetic and environmental factors.
Our research is focused on applying a globally inclusive patient-derived model, which includes cutting-edge multi-omic technologies and computational big data science, to identify factors contributing to PCa health disparities, while providing an all-inclusive roadmap for predicting, treating and ultimately preventing PCa (prediction medicine).
As African men are most impacted by PCa, it was critical that the team have a major focus on the African continent. This was an easy match for Professor Vanessa Hayes, with her roots in southern Africa. However, genomic data has been lacking for the continent.
From generating the first African genomes published in Nature 2010, the team has led studies in southern Africa, home to genetically the most diverse human populations, including the click-speaking peoples from the broadly defined San and Khoe ethnolinguistic groups.
Through collaboration across the continent, the team has been defining the extent of human genetic diversity, while highlighting the significant role southern Africa has played and continues to play in our evolution as modern humans.
Prostate cancer (PCa) evolves through the acquisition of genomic events, ranging from cancer drivers to passengers. However, these passengers are not always just bystanders, but represent variant patterns (signatures) of clinically relevant tumour types (molecular taxonomies) and/or potential carcinogenic exposures.
These drivers and taxonomies in turn impact specific molecular pathways critical for genomic maintenance, while providing critical insights into underlying PCa geo-ancestral health disparities.
Here, using tumour derived whole genome, transcriptome and epigenome interrogation, we're not only defining the landscape of ancestral PCa disparity, but in turn linking this disparity to patient-matched exposure data, known as exposomics.
Prostate cancer (PCa) is biologically complex, with significant intra-tumoral genomic heterogeneity having a direct impact on disease predisposition, progression, outcomes and response to treatment (precision medicine).
Most notably and unlike other solid tumours, PCa commonly acquires complex genomic regulators defined by structural variations and both regional and chromosomal copy number alterations (gains/losses), over small/simple nucleotide changes.
Furthermore, these large complex events may be inherited, while known to cause rare genetic conditions, the role is less established in cancers such as PCa.
We're using computational tools and alternative genomic technologies, from long-read sequencing to digital karyotyping, to reveal the full spectrum of tumour genomic complexity, which we have termed the ‘structome’.
Our researchers have established a non-sequencing digital karyotyping or optical genome mapping (OGM) laboratory housing the Bionano Saphyr gen2 instrument.
Besides our own research focused on elucidating both the human and cancer structome, while building telomere-to-telomere finished genomes, we are open to collaborations across NSW and Australia.
Most notably, we have assisted with clinical projects associated with diagnosing rare neuromuscular conditions commonly impacted by large inherited events.
For queries, please contact the OGM lab manager Dr Md. Mehedi Hasan
Prostate cancer (PCa) is highly heritable, with family history and patient ancestry a significant risk factor, pointing to the significance of genetic inheritance as a predisposing factor. \
Currently, blood-based prostate specific antigen (PSA) testing is the ‘golden standard’ biomarker for PCa risk and disease relapse. In turn, one’s genetics has the potential to predict disease course and treatment response.
While much research has focused on men of European ancestry, those most impacted by PCa associated deaths are less likely to benefit from PCa screening programs.
We're establishing ancestrally equitable screening criteria, including from establishing population-specific criteria for blood-based biomarker use, to the identification of gene panels for rare pathogenic risk screening, and the identification of common risk alleles to establish all-inclusive polygenetic risk scores.
Over 90% of genomic data and over 98% of prostate cancer genomic data is European derived, which has led to genomic tools and pipelines largely unfavourable for non-European and minority populations.
It is therefore critical that computational models used from human reference genomes to variant calling and prediction models be trained and developed using ancestry inclusive data.
We're actively involved in generating population inclusive genomic pipelines required for all projects addressing PCa health disparities. These developments being applicable to other cancers and disease types.
Our Computational Genomics Group focuses on establishing ancestry appropriate short and long-read informatic pipelines for big data processing and variant discovery, telomere-to-telomere (T2T) genome finishing and multi-omic integration, using mathematical and computational analytics and tool development, from machine learning to quantum computing, to provide tumour classification and clinical associations.
Dr Jaratlerdsiri is a key partner of the Ancestry and Health Genomics Laboratory and the Sydney Informatics Hub.
Team members
Southern African Khoe-San peoples represent modern humans earliest diverged populations and as such genetically the most diverse human populations.
These populations have therefore not only played a critical role in understanding of modern human evolution and adaption to our environment, but they also provide a critical resource for cataloguing the extent of human genome diversity with associated medical impact.
After 15-years of community engagement with the Khoe-San click-speaking and largely forager peoples of Namibia, Professor Vanessa Hayes has developed a deep relationship with the communities with whom she has engaged, and discussing the genomic discoveries to the communities and their leaders.
Over this extensive period, the team has established a unique resource of benefit to the greater medical research community.
Mailing address
Level 3
Charles Perkins Centre
University of Sydney
NSW, 2050
