A5054647246- Microbial Metabolic Engineering and Bioproduction
- Genetic Neurodegenerative Diseases
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- Amyotrophic Lateral Sclerosis Research
- Genetic Associations and Epidemiology
- Gene Regulatory Network Analysis
- Neurogenetic and Muscular Disorders Research
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Neurological diseases and metabolism
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Gene expression and cancer classification
- Liver Disease Diagnosis and Treatment
- Glycogen Storage Diseases and Myoclonus
- Adipokines, Inflammation, and Metabolic Diseases
- Parkinson's Disease Mechanisms and Treatments
- RNA regulation and disease
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- DNA Repair Mechanisms
- Machine Learning in Healthcare
The University of Melbourne
2015-2025
Walter and Eliza Hall Institute of Medical Research
2019-2025
Murdoch Children's Research Institute
2022-2024
Genomics (United Kingdom)
2016
The University of Queensland
2012-2013
Australian Research Council
2013
The cerebellar ataxias (CAs) are a heterogeneous group of disorders characterized by progressive incoordination. Seventeen repeat expansion (RE) loci have been identified as the primary genetic cause and account for >80% diagnoses. Despite this, diagnostic testing is limited inefficient, often utilizing single gene assays. This study evaluates effectiveness long- short-read sequencing tools CA. We recruited 110 individuals (48 females, 62 males) with clinical diagnosis Short-read genome...
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited manifesting with ptosis, dysphagia and distal weakness. Pathologically it characterised by rimmed vacuoles intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified OPDM individuals Asian populations. None of these have been found affected non-Asian ancestry. this study we describe the identification expansions ABCD3 , ranging from 118 to 694 repeats, 35 across...
Network modules—topologically distinct groups of edges and nodes—that are preserved across datasets can reveal common features organisms, tissues, cell types, molecules. Many statistics to identify such modules have been developed, but testing their significance requires heuristics. Here, we demonstrate that current methods for assessing module preservation systematically biased produce skewed p values. We introduce NetRep, a rapid computationally efficient method uses permutation approach...
Abstract Remodelling of chromatin architecture is known to regulate gene expression and has been well characterized in cell lineage development but less so response perturbation. Activation T cells, which triggers extensive changes transcriptional programs, serves as an instructive model elucidate how orchestrate To characterize coordinate at different levels architecture, we analyzed accessibility, chromosome conformation activated human cells. activation was by widespread accessibility...
Pathogenic short tandem repeat (STR) expansions cause over 20 neurodegenerative diseases. To determine the contribution of STRs in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), we used ExpansionHunter, REviewer, polymerase chain reaction validation to assess 21 disease-associated whole-genome sequencing data from 608 patients with ALS, 68 FTD, 4703 matched controls. We also propose a data-derived outlier detection method for defining allele thresholds rare...
Epithelial-mesenchymal transition (EMT) is a reversible transcriptional program invoked by cancer cells to drive progression. Transcription factor ZEB1 master regulator of EMT, driving disease recurrence in poor-outcome triple negative breast cancers (TNBCs). Here, this work silences TNBC models CRISPR/dCas9-mediated epigenetic editing, resulting highly-specific and nearly complete suppression vivo, accompanied long-lasting tumor inhibition. Integrated "omic" changes promoted dCas9 linked...
Immunometabolism plays a central role in many cardiometabolic diseases. However, robust map of immune-related gene networks circulating human cells, their interactions with metabolites, and genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, genomic profiles from two population-based cohorts (total N = 2168), including subset individuals matched multi-omic data at 7-year follow-up. We identify topologically replicable enriched for diverse immune functions...
Numerical variations and transitional anatomy in the human vertebral column, observed up to 36% of individuals, represent a significant yet understudied aspect skeletal development with potential effects on multiple physiological systems. Utilising UK Biobank data, we integrated genetic analysis deep learning–based multi–modal body imaging investigate factors associated thoracic lumbar spine anatomy. We identified three key genes– GPC3 , NR6A1 VRTN –associated numerical vertebrae ribs,...
Repeat expansions (REs) may be Parkinson's disease (PD) risk factors. We screened whole genome sequencing data from the AMP PD Lewy Body Dementia (LBD) and cohorts for 37 REs associated with other neurological disorders, identified both interrupted uninterrupted CAG in ATXN2 4/2,431 2/2,468 LBD cases, but none controls. These findings suggest pleiotropy certain PD.
We describe FoundHaplo, an identity-by-descent algorithm that can be used to screen untyped disease-causing variants using single nucleotide polymorphism (SNP) array data. FoundHaplo leverages knowledge of shared disease haplotypes for inherited identify those who share the haplotype and are, therefore, likely carry rare [minor allele frequency (MAF) ≤ 0.01%] variant. performed a simulation study evaluate performance across 33 disease-harbouring loci. was infer presence two (MAF 0.01%)...
Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition for which novel disease modifying therapies are urgently needed. Given the increasing bottlenecks in drug discovery pipelines, repurposing existing drugs ALS may represent path to expedite translation and improve outcomes. However, heterogeneous aetiology remains poorly characterised, complicating efforts effectively repurpose drugs. We propose that polygenic architecture of genetic liability, ranges...
Abstract Mitochondrial dysfunction plays an important role in Parkinson’s disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for health. We investigated the links between blood mtDNA-CN and PD severity risk using Accelerating Medicines Partnership program Disease dataset, replicating our results UK Biobank. Our findings reveal that reduced levels are associated heightened increased of motor symptoms olfactory dysfunction. estimated cell composition...
Abstract Bioinformatic methods for detecting short tandem repeat expansions in short-read sequencing have identified new humans, but require alignment information to identify repetitive motif enrichment at genomic locations. We present superSTR, an ultrafast method that does not alignment. superSTR is used process whole-genome and whole-exome data, perform the first STR analysis of UK Biobank, efficiently screening identifying known potential disease-associated STRs exomes 49,953 biobank...
ABSTRACT Individuals affected by inherited neuromuscular diseases often present with a specific pattern of muscle weakness, which can guide clinicians in genetic investigations and variant interpretation. Nonetheless, more than 50% cases do not receive diagnosis. Oculopharyngodistal myopathy (OPDM) is an manifesting particular combination ptosis, dysphagia distal weakness. Pathologically it characterised rimmed vacuoles intranuclear inclusions on biopsy. In recent years GCC • CCG repeat...
<ns3:p>COVID-19 caused by SARS-CoV-2 has resulted in a global pandemic with rapidly developing health and economic crisis. Variations the disease have been observed associated genomic sequence of either human host or pathogen. Worldwide scientists scrambled initially to recruit patient cohorts try identify risk factors. A resource that presented itself early on was UK Biobank (UKBB), which is investigating respective contributions genetic predisposition environmental exposure development...
Large quantities of information describing the mechanisms biological pathways continue to be collected in publicly available databases. At same time, experiments have increased scale, and biologists increasingly use defined online databases interpret results generate hypotheses. Emerging computational techniques that exploit rich captured reaction systems require formal standardized descriptions extract these networks avoid alternative: time-consuming largely manual literature-based network...
Curated databases of signal transduction have grown to describe several thousand reactions, and efficient use these data requires the development modelling tools elucidate explore system properties. We present PATHLOGIC-S, a Boolean specification for signalling model, with its associated GPL-licensed implementation using integer programming techniques. The PATHLOGIC-S has been designed function on current desktop workstations, is capable providing analyses some largest currently available...
Abstract The interaction between metabolism and the immune system plays a central role in many cardiometabolic diseases. We integrated blood transcriptomic, metabolomic, genomic profiles from two population-based cohorts, including subset with 7-year follow-up sampling. identified topologically robust gene networks enriched for diverse functions cytotoxicity, viral response, B cell, platelet, neutrophil, mast cell/basophil activity. These modules showed complex patterns of association 158...