A5018252802- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Bioinformatics and Genomic Networks
- Cancer Cells and Metastasis
- Gene expression and cancer classification
- Single-cell and spatial transcriptomics
- Glioma Diagnosis and Treatment
- Machine Learning in Bioinformatics
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- Biomedical Text Mining and Ontologies
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Advanced Breast Cancer Therapies
- Computational Drug Discovery Methods
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Renal and related cancers
- Barrier Structure and Function Studies
The University of Melbourne
2016-2025
Walter and Eliza Hall Institute of Medical Research
2016-2025
The University of Queensland
2010-2025
The University of Adelaide
2023-2025
Centre for Cancer Biology
2023-2025
Yale University
2023-2024
Parks Victoria
2024
Translational Research Institute
2023
Institute of Clinical Research
2023
Cancer Institute (WIA)
2023
This study describes comprehensive polling of transcription start and termination sites analysis previously unidentified full-length complementary DNAs derived from the mouse genome. We identify 5' 3' boundaries 181,047 transcripts with extensive variation in arising alternative promoter usage, splicing, polyadenylation. There are 16,247 new protein-coding transcripts, including 5154 encoding proteins. Genomic mapping transcriptome reveals transcriptional forests, overlapping on both...
Gene set scoring provides a useful approach for quantifying concordance between sample transcriptomes and selected molecular signatures. Most methods use information from all samples to score an individual sample, leading unstable scores in small data sets introducing biases composition (e.g. varying numbers of different cancer subtypes). To address these issues, we have developed truly single method, associated R/Bioconductor package singscore ( https://bioconductor.org/packages/singscore...
Each omics platform is now able to generate a large amount of data. Genomics, proteomics, metabolomics, interactomics are compiled at an ever increasing pace and form core part the fundamental systems biology framework. Recently, several integrative approaches have been proposed extract meaningful information. However, these lack visualisation outputs fully unravel complex associations between different biological entities.The multivariate statistical 'regularized Canonical Correlation...
Natural killer (NK) cell activity is essential for initiating antitumor responses and may be linked to immunotherapy success. NK cells other innate immune components could exploitable cancer treatment, which drives the need tools methods that identify therapeutic avenues. Here, we extend our gene-set scoring method singscore investigate infiltration by applying RNA-seq analysis samples from bulk tumors. Computational have been developed deconvolution of types within solid We taken gene...
The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling mouse epithelial cells spanning four developmental stages in post-natal gland. Notably, undergoes a large-scale shift gene expression from relatively homogeneous basal-like program pre-puberty to distinct lineage-restricted programs puberty. Interrogation...
Purpose Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate have been proposed COVID-19. However, at present, there is no consensus on the best diagnostic approach to in infected patients. Moreover, it not clear whether such tools would apply other potentially pandemic pathogens therefore of use as stockpile future preparedness. Methods We conducted a multi-cohort observational study...
Inference of gene regulatory network from expression data is a challenging task. Many methods have been developed to this purpose but comprehensive evaluation that covers unsupervised, semi-supervised and supervised methods, provides guidelines for their practical application, lacking.
Altered networks of gene regulation underlie many complex conditions, including cancer. Inferring regulatory from high-throughput microarray expression data is a fundamental but challenging task in computational systems biology and its translation to genomic medicine. Although diverse statistical approaches have been brought bear on the network inference problem, their relative strengths disadvantages remain poorly understood, largely because comparative analyses usually consider only small...
To identify biologically relevant groupings or clusters of nuclear receptors (NR) that are associated with breast neoplasia, potentially diagnostic, discriminant prognostic value, we quantitated mRNA expression levels all 48 members the human NR superfamily by TaqMan low-density array analysis in 116 curated tissue samples, including pre- and postmenopausal normal both ERα+ ERα− tumor tissue. In addition, have determined independent cohorts tamoxifen-treated samples. There were differences...
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, functioning in part by facilitating the degradation target mRNAs. They have an established role controlling epithelial-mesenchymal transition (EMT), a reversible phenotypic program underlying normal and pathological processes. Many studies demonstrate individual miRNAs using overexpression at levels greatly exceeding physiological abundance. This can influence transcripts with relatively poor targeting may...
Aberrant changes in epigenetic mechanisms such as histone modifications play an important role cancer progression. PRMT1 which triggers asymmetric dimethylation of H4 on arginine 3 (H4R3me2a) is upregulated human colorectal (CRC) and essential for cell proliferation. However, how this dysregulated modification might contribute to malignant transitions CRC remains poorly understood.In study, we integrated biochemical assays including protein interaction studies chromatin immunoprecipitation...
Abstract Purpose: Bioinformatics analysis followed by in vivo studies patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 MYC-amplified tumors that have the worst clinical prognosis. Experimental Design: A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was potential novel targets. The top hit this validated using PDX...
Despite increasing recognition of the importance GM-CSF in autoimmune disease, it remains unclear how is regulated at sites tissue inflammation. Using fate reporter mice, we show that synovial NK cells produce autoantibody-mediated inflammatory arthritis. Synovial promote a neutrophilic cell infiltrate, and persistent arthritis, via production, as deletion cells, or specific ablation production abrogated disease. IL-18–dependent. Furthermore, cytokine-inducible SH2-containing protein (CIS)...
Abstract The recognition of the immune system as a key component tumor microenvironment (TME) led to promising therapeutics. Because such therapies benefit only subsets patients, understanding activities cells in TME is required. Eosinophils are an integral part especially mucosal tumors. Nonetheless, their role and environmental cues that direct largely unknown. We report breast cancer lung metastases characterized by resident recruited eosinophils. Eosinophil recruitment metastatic sites...
KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate H3K23 exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of to achieve therapeutic benefit has been a challenge. Here we describe identification highly potent, selective, orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from benzisoxazole series, which demonstrates anti-tumor...
To gain a better understanding of the complexity gene expression in normal and diseased tissues it is important to account for spatial context identity cells situ. State-of-the-art profiling technologies, such as Nanostring GeoMx Digital Spatial Profiler (DSP), now allow quantitative spatially resolved measurement transcriptome tissues. However, bioinformatics pipelines currently used analyse data often fail successfully technical variability within experimental designs, thus limiting...
Mucosal head and neck squamous cell carcinoma (HNSCC) are the seventh most common cancer, with approximately 50% of patients living beyond 5 years. Immune checkpoint inhibitors (ICIs) have shown promising results in recurrent or metastatic (R/M) disease, however, only a subset benefit from immunotherapy. Studies implicated tumor microenvironment (TME) HNSCC as major factor therapy response, highlighting need to better understand TME, particularly by spatially resolved means determine...
Abstract Spatial molecular data has transformed the study of disease microenvironments, though, larger datasets pose an analytics challenge prompting direct adoption single-cell RNA-sequencing tools including normalization methods. Here, we demonstrate that library size is associated with tissue structure and normalizing these effects out using commonly applied scRNA-seq methods will negatively affect spatial domain identification. should not be specifically corrected for prior to analysis,...
Developing vaccines that promote CD8+ T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1+ stem cell–like (TSCM) cells are important determinants of long-lived memory. Yet, the developmental requirements TSCM formation unclear. Here, we identify temporal window type I interferon receptor (IFNAR) blockade to drive generation following viral infection mRNA–lipid nanoparticle vaccination. We reveal reversible trajectory where transcriptionally distinct emerged...
Abstract Motivation Biomarker discovery is important and offers insight into potential underlying mechanisms of disease. While existing biomarker identification methods primarily focus on single cell RNA sequencing (scRNA-seq) data, there remains a need for automated designed labeled bulk RNA-seq data from sorted populations or experiments. Current require curation results statistical thresholds may not account tissue background expression. Here we bridge these limitations with an marker...
ABSTRACT. Although many of the molecular interactions in kidney development are now well understood, molecules involved specification metanephric mesenchyme from surrounding intermediate mesoderm and, hence, formation renal progenitor population poorly characterized. In this study, cDNA microarrays were used to identify genes enriched murine embryonic day 10.5 (E10.5) uninduced mesenchyme, population, comparison with more rostral derivatives mesoderm. Microarray data analyzed using R...