The funding from the MRFF’s Genomics Health Futures Mission will support research to harness the full potential of genomic data to improve diagnosis and inform clinical care for all patients who have undergone genetic or genomic testing in Australia.
The international team of researchers and clinicians, led by WEHI computational biologist Dr Alan Rubin, will aim to address some of the biggest barriers holding back the use of genomic data in clinical care and gain new insights into blood, breast and ovarian cancers.
Dr Rubin said national and international biological databases contained a wealth of genetic information but combining the data and interpreting it accurately was a major challenge.
“Diagnosing genetic diseases is difficult because subtle changes can be harmful but we don’t always know which changes are benign and which ones may contribute to disease,” he said.
“More than half of the genomic variants catalogued in clinical databases can’t be used to inform diagnosis and treatment because we don’t have enough information to say whether they’re significant for a patient’s health or not.
“With new technologies we can now examine every possible change in a single gene in one experiment, but what we’re missing is an easy way to share this data and cross-reference it with what we see in patients – this project will bridge that critical gap.”
The international research team led by Dr Rubin includes chief investigators from the QIMR Berghofer Medical Research Institute, the Centre for Cancer Biology, the Peter MacCallum Cancer Centre, the University of Washington and NSW Health Pathology.
Working with 15 clinical and research partners, the team will develop technology to link two vital data platforms to enable rapid clinical translation, use the technology to investigate cancer-related genes and educate clinicians across Australia on how to interpret and apply the data to improve patient health.
The development of a new type of experiment – known as multiplexed assays of variant effect (MAVEs) – has revolutionised our ability to understand the function of genes and their roles in disease.
MAVEs offer a way for researchers to systematically measure the impact of tens of thousands of individual genetic variants on the function of a gene in a single well-controlled experiment.
“Data obtained from MAVEs has many applications, from understanding the fundamentals of how a gene or protein functions to measuring the potential role of genetic variants in a disease,” Dr Rubin said.
“But the data can be difficult to access and interpret, so the information is not widely used and MAVEs are still slow to impact clinical care.”
This new three-year project will link MaveDB, the first dedicated repository of MAVE data, with Shariant, a platform for sharing clinical variant interpretations between Australian clinical molecular pathology laboratories.
Connecting the two platforms will enable laboratories to use MAVE data to improve genetic diagnosis across a broad range of diseases.
Dr Rubin said the project would also provide support for variant curation tools and integrate with other Australian genomic resources.
“These efforts will enable Australian labs to more easily access existing and forthcoming MAVE data from a global network of researchers,” he said.
Using state-of-the-art experimental techniques, the project will also generate new MAVE data to help classify patient variants and inform treatment options for blood, breast and ovarian cancers.
The research will focus on genetic variants in blood cancer genes RUNX1 and GATA2, as well as PARPi, a class of targeted cancer therapeutics rapidly emerging as the standard of care in ovarian cancer. Researchers will work to overcome resistance, a key issue with PARPi.
The project will also investigate how differences distributed across breast cancer patient genomes may affect the risk associated with specific genetic variants in the BRCA1 gene.
This research will demonstrate a new approach with potential to improve the accuracy of genetic diagnosis that can be used for a wide range of diseases where common genetic variation can help predict risk.
WEHI Director, Professor Doug Hilton AO, said the project was a fantastic example of multi-disciplinary collaboration to support transformative discoveries and improve clinical outcomes.
“We are thrilled to receive funding from the MRFF for this significant project, which will harness WEHI’s expertise in bioinformatics and bring together leaders across molecular pathology and cancer research,” Professor Hilton said.
“It is wonderful to see the innovative MaveDB database, co-developed at WEHI with international collaborators, deployed to help clinicians make a difference to patients.
“This project will create a virtuous cycle, where data can inform clinical care and patient need can in turn drive research priorities.
“It demonstrates how bioinformatics and computational biology are revolutionising the way medical research is undertaken and WEHI is excited to be at the forefront of this transformation.”
WEHI Chief Investigators on the project are Dr Alan Rubin, Dr Belinda Phipson and Dr Matthew Wakefield, with Professor Clare Scott as an Associate Investigator.
Lead institutions: WEHI, QIMR Berghofer Medical Research Institute, Centre for Cancer Biology, SA Pathology, Peter MacCallum Cancer Centre, University of Washington, NSW Health Pathology.
Project partners: Australian Genomics, Children’s Cancer Institute, Global Alliance for Genomics and Health, Human Genetics Society of Australasia, Leukaemia Foundation, Murdoch Children’s Research Institute, NSW Health Pathology, Omico, Pathology Queensland, PathWest, SA Pathology, Telethon Kids Institute, The RUNX1 Research Program, University of South Australia, Victorian Clinical Genetics Services.
Also involved as Associate Investigators are researchers from the Garvan Institute of Medical Research and National Institutes of Health (US).
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