Indigenous telomere-2-telomere human reference genomes to enable discovery, translation and innovations

Our project will generate ten telomere-2-telomere (T2T) reference genomes to represent distinct Indigenous communities using long (PacBio HiFi, ONT) and linked read (HiC) DNA sequencing technologies. We will develop innovative software for reference guided de novo genome assemblies for improved accuracy and the graph-based representation for variant discovery and multi-omic analysis (transcriptomics and epigenetics). Second, we will discover mutational processes of complex structural variations and sex-chromosomes to understand their roles in disease and health using Indigenous T2T genomes. Third, we will demonstrate the clinical utility and translation benefits of Indigenous T2T genomes by performing genomic analysis of patients enrolled in the Australian Undiagnosed Diseases Network.