A5066455544- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Virus-based gene therapy research
- Cancer-related Molecular Pathways
- Bioinformatics and Genomic Networks
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Immune Cell Function and Interaction
- Methane Hydrates and Related Phenomena
- T-cell and B-cell Immunology
- Hair Growth and Disorders
- Cell death mechanisms and regulation
- Birth, Development, and Health
- Angiogenesis and VEGF in Cancer
- Probability and Risk Models
The University of Melbourne
2015-2025
Walter and Eliza Hall Institute of Medical Research
2015-2025
Abstract New normal linear modeling strategies are presented for analyzing read counts from RNA-seq experiments. The voom method estimates the mean-variance relationship of log-counts, generates a precision weight each observation and enters these into limma empirical Bayes analysis pipeline. This opens access analysts to large body methodology developed microarrays. Simulation studies show that performs as well or better than count-based methods even when data generated according...
A flexible statistical framework is developed for the analysis of read counts from RNA-Seq gene expression studies. It provides ability to analyse complex experiments involving multiple treatment conditions and blocking variables while still taking full account biological variation. Biological variation between RNA samples estimated separately technical associated with sequencing technologies. Novel empirical Bayes methods allow each have its own specific variability, even when there are...
<ns4:p>In recent years, RNA sequencing (RNA-seq) has become a very widely used technology for profiling gene expression. One of the most common aims RNA-seq is to identify genes or molecular pathways that are differentially expressed (DE) between two more biological conditions. This article demonstrates computational workflow detection DE and from data by providing complete analysis an experiment epithelial cell subsets in mouse mammary gland. The uses R software packages open-source...
<ns4:p>In recent years, RNA sequencing (RNA-seq) has become a very widely used technology for profiling gene expression. One of the most common aims RNA-seq is to identify genes or molecular pathways that are differentially expressed (DE) between two more biological conditions. This article demonstrates computational workflow detection DE and from data by providing complete analysis an experiment epithelial cell subsets in mouse mammary gland. The uses R software packages open-source...
To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1
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...
Abstract edgeR is an R/Bioconductor software package for differential analyses of sequencing data in the form read counts genes or genomic features. Over past 15 years, has been a popular choice statistical analysis from technologies such as RNA-seq ChIP-seq. pioneered use negative binomial distribution to model count with replicates and generalized linear models analyse complex experimental designs. implements empirical Bayes moderation methods allow reliable inference when number small....
Abstract edgeR is an R/Bioconductor software package for differential analyses of sequencing data in the form read counts genes or genomic features. Over past 15 years, has been a popular choice statistical analysis from technologies such as RNA-seq ChIP-seq. pioneered use negative binomial distribution to model count with replicates and generalized linear models analyze complex experimental designs. implements empirical Bayes moderation methods allow reliable inference when number small....
Abstract Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) track the spatio-temporal fate thousands barcoded clones in primary tumors, their metastases. Tumor resection had a major impact on reducing clonal diversity secondary sites, indicating that most disseminated tumor cells lacked...
Abstract Bone marrow is a preferred metastatic site for multiple solid tumours and associated with poor prognosis significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone to support their long-term propagation, but precise location mechanisms mediate niche interactions are unknown. Using breast as model of tumour metastasis marrow, we applied large-scale quantitative three-dimensional imaging characterise temporal changes in...
Abstract Whole genome bisulphite sequencing (WGBS) permits the genome-wide study of single molecule methylation patterns. One key goals mammalian cell-type identity studies, in both normal differentiation and disease, is to locate differential patterns across genome. We discuss most desirable characteristics for DML (differentially methylated locus) DMR region) detection tools a context choose set statistical methods that fully or partially satisfy these considerations compare benchmarking....
Abstract Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here, we have applied longitudinal single-cell transcriptome profiling >45,000 fibroblasts mouse gland across five different developmental stages during oncogenesis. In gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes adipogenesis-regulatory, as well cycling puberty pregnancy. These specialized cell types appear to emerge from...
<ns4:p>Studies in epigenetics have shown that DNA methylation is a key factor regulating gene expression. Aberrant often associated with instability, which could lead to development of diseases such as cancer. typically occurs CpG context. When located promoter, acts repress transcription and The most commonly used technology studying bisulfite sequencing (BS-seq), can be measure genomewide levels on the single-nucleotide scale. Notably, BS-seq also combined enrichment strategies, reduced...
<ns4:p>Cytosine methylation is an important DNA epigenetic modification. In vertebrates, occurs at CpG sites, which are dinucleotides where a cytosine immediately followed by guanine in the sequence from 5' to 3'. When located promoter region of gene, often associated with transcriptional silencing gene. Aberrant development various diseases such as cancer. Bisulfite sequencing (BS-seq) current "gold-standard" technology for high-resolution profiling methylation. Reduced representation...
Abstract Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, post-involution, as well transcriptomes of micro-dissected terminal end buds (TEBs) subtending ducts...
Background Spatial transcriptomics allows gene expression to be measured within complex tissue contexts. Among the array of spatial capture technologies available is 10x Genomics’ Visium platform, a popular method which enables transcriptomewide profiling sections. offers range sample handling and library construction methods introduces need for benchmarking compare data quality assess how well technology can recover expected features biological signatures. Results Here we present...
Significance Understanding the intrinsic mechanisms underlying formation of humoral memory during infection and ability population to persist for long periods time is important identifying potential targets improving efficacy vaccines. Here we demonstrate that chromatin modifier MOZ regulates B-cell formation, controlling compartment composition. This activity B cell-intrinsic required establishing germinal center gene expression program. IgM cells have been implicated in maintaining over...
Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical establishing effective antibody-mediated responses, yet it unknown how B cells integrate pathogen-induced signals drive or suppress transcriptional programs specialized for each class pathogen. Here, we detail role factor c-Myb in regulating T-bet-mediated anti-viral program. Deletion mature significantly increased serum IgG2c CXCR3 expression by...
Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins molecular processes that contribute to SqCC formation are largely unexplored. Here we show human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor counterparts have limited colony-forming capacity. We demonstrate this difference arises in part because...