TRIAGE: A disease agnostic computational and modelling platform to accelerate variant classification (Old ID 27849)
Role
Principal Investigator
Description
This proposal develops a disease-agnostic, high throughput and scalable functional genomics platform integrating computational variant prediction and disease modelling to increase the diagnostic rate of unresolved cases and accelerate development of experimental therapeutics. We implement a novel unsupervised, disease agnostic, genome-wide computational analysis method called TRIAGE which provides predictions at single base resolution across the human genome, revealing the likelihood of a variant being pathogenic. No other methods compare with TRIAGE in identifying genes associated with developmental process and cell differentiation where variants in these loci are associated with congenital disease and multi-organ syndromes. Our team of experts across Australia’s research and clinical sectors bring skills in bioinformatics, statistical genetics, clinical genetics, and disease modelling. In Aim 1 we incorporate tested genome-wide metrics, such as TRIAGE, to build open access machine learning methods that enhance variant prediction in clinical data. Aim 2 implements TRIAGE in Australian Genomic cohorts and registries to identify prioritised and novel candidates for disease modelling and develop strategies and guidelines for advancing TRIAGE in clinical genetic diagnostics and functional genomics networks. Aim 3 uses TRIAGE to prioritise variants for disease modelling across a multi-institutional phenotyping platform. Disease modelling includes innovative genome-wide molecular phenotyping coupled with physiological assays in cell and animal models. At the completion of the grant, we aim to implement TRIAGE in standard clinical genetic analysis protocols and deliver phenotyping data to assist in classification of unresolved genetic diseases. These achievements will result in diagnoses and mechanism of disease that will directly benefit patients in obtaining medical and psychosocial support and create pathways to new therapies.
Date
01 Jun 2022 - 31 May 2026
Project Type
GRANT
Keywords
Congenital disease;Functional Genomics;Embryonic stem cells;Disease modelling;Bioinformatics
Funding Body
Commonwealth Department of Health
Amount
180333
Project Team
N/A