ORCID Profile
0000-0001-6358-526X
Current Organisations
The Harry Perkins Institute of Medical Research
,
University of Western Australia
,
UNSW Sydney
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Publisher: Elsevier BV
Date: 03-2023
Publisher: Zenodo
Date: 2016
Publisher: Emerald
Date: 24-10-2008
DOI: 10.1108/01435120810917332
Abstract: The purpose of this article is to explore barriers and motivators for new professionals who write and present for the professional literature. Authors from the ALIA New Librarians' Symposium held in December 2006 in Sydney, Australia were surveyed about their experiences of writing and presenting early in their career. The author of this paper was the symposium's programme coordinator. The majority of authors were working in Australia, and few were required to write or present as part of their work role. In the absence of this requirement, factors that motivate new professionals to write can be difficult to define. Barriers to writing include time, skills, and responsibilities outside work. The paper discusses a publishing opportunity aimed at new professionals and other strategies to reduce barriers to writing and presenting.
Publisher: Cold Spring Harbor Laboratory
Date: 18-04-2018
DOI: 10.1101/303552
Abstract: Tuberculosis is a life-threatening infectious disease caused by Mycobacterium tuberculosis ( M.tb ). M.tb subverts host immune responses to build a favourable niche and survive inside of host macrophages. Macrophages can control or eliminate the infection, if appropriate transcriptional programs are activated. The role of transcriptional enhancers in the activation and maintenance of these programs remains unexplored. We analysed transcribed enhancers in M.tb -infected mouse bone marrow-derived macrophages. We established a link between known M.tb -responsive transcription factors and transcriptional activation of enhancers and their target genes. Our data suggest that enhancers might drive the macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. We report enhancers acquiring transcription de novo upon infection. Finally, we link highly transcriptionally induced enhancers to the activation of genes with previously unappreciated roles in M.tb infection, such as Fbxl3, Tapt1, Edn1, and Hivep1. Our findings extend current knowledge of the regulation of macrophage responses to M.tb infection and provide a basis for future functional studies on enhancer-gene interactions in this process.
Publisher: Oxford University Press (OUP)
Date: 03-04-2018
Publisher: Zenodo
Date: 2016
Publisher: Oxford University Press (OUP)
Date: 26-04-2019
DOI: 10.1093/BIOINFORMATICS/BTZ292
Abstract: Single-cell RNA sequencing (scRNA-seq) measures gene expression at the resolution of in idual cells. Massively multiplexed single-cell profiling has enabled large-scale transcriptional analyses of thousands of cells in complex tissues. In most cases, the true identity of in idual cells is unknown and needs to be inferred from the transcriptomic data. Existing methods typically cluster (group) cells based on similarities of their gene expression profiles and assign the same identity to all cells within each cluster using the averaged expression levels. However, scRNA-seq experiments typically produce low-coverage sequencing data for each cell, which hinders the clustering process. We introduce scMatch, which directly annotates single cells by identifying their closest match in large reference datasets. We used this strategy to annotate various single-cell datasets and evaluated the impacts of sequencing depth, similarity metric and reference datasets. We found that scMatch can rapidly and robustly annotate single cells with comparable accuracy to another recent cell annotation tool (SingleR), but that it is quicker and can handle larger reference datasets. We demonstrate how scMatch can handle large customized reference gene expression profiles that combine data from multiple sources, thus empowering researchers to identify cell populations in any complex tissue with the desired precision. scMatch (Python code) and the FANTOM5 reference dataset are freely available to the research community here orrest-lab/scMatch. Supplementary data are available at Bioinformatics online.
Publisher: Informa UK Limited
Date: 03-07-2022
Publisher: National Information Standards Organization (NISO)
Date: 2009
Publisher: Emerald
Date: 27-11-2009
DOI: 10.1108/14678040911014167
Abstract: This paper aims to talk briefly about IFLA's experiences with funders' evaluation requirements and the difficulties of finding an evaluation methodology that is appropriate for the type of international activities IFLA engages in. This review is based on IFLA's decision to increase the emphasis on evaluating the impact of its activities, especially through the use of impact assessment. The method was used as a trial in 2009 to evaluate FAIFE's activities. This paper discusses the need for success stories and best practice in IFLA's advocacy work, and suggests that impact assessment offers a way to show the real value of library work to key partners and stakeholders. The paper presents an overview of current thinking and progress in IFLA.
Publisher: SAGE Publications
Date: 06-2011
Publisher: Zenodo
Date: 2019
Publisher: Zenodo
Date: 2019
Publisher: SAGE Publications
Date: 12-2010
Abstract: An introduction to the Building Strong Library Associations programme of the International Federation of Library Associations and Institutions. The programme is rolled out through country projects which include workshops, specialist mentoring, online blended activities and specially developed cross-programme activities. Three country projects per year will be implemented from 2010 until 2012, one each in Africa, Asia and Oceania, and Latin America and the Caribbean. The programme will be evaluated on three levels with a view towards ensuring sustainability of the programme and each country project.
Publisher: Cold Spring Harbor Laboratory
Date: 09-2021
DOI: 10.1101/MCS.A006111
Abstract: Tumor heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition of tumor heterogeneity is critical in the clinical management of cancer patients. Here, we utilized single-cell RNA sequencing (scRNA-seq) to uncover the intra- and intertumoral heterogeneity of liver metastases from a patient with metastatic uveal melanoma. The two metastases analyzed were largely infiltrated by noncancerous cells with significant variability in the proportion of different cell types. Analysis of copy-number variations (CNVs) showed gain of 8q and loss of 6q in both tumors, but loss of Chromosome 3 was only detected in one of the tumors. Single-nucleotide polymorphism (SNP) array revealed a uniparental isodisomy 3 in the tumor with two copies of Chromosome 3, indicating a regain of Chromosome 3 during the development of the metastatic disease. In addition, both tumors harbored subclones with additional CNVs. Pathway enrichment analysis of differentially expressed genes revealed that cancer cells in the metastasis with isodisomy 3 showed up-regulation in epithelial–mesenchymal transition and myogenesis related genes. In contrast, up-regulation in interferon signaling was observed in the metastasis with monosomy 3 and increased T-cell infiltrate. This study highlights the complexity and heterogeneity of different metastases within an in idual case of uveal melanoma.
Publisher: SAGE Publications
Date: 10-2009
Abstract: This paper explores the changing work environment in libraries and information management and the impact on new professionals and new graduates. New graduates need to have their own support networks and targeted professional development to successfully navigate job and sector changes and to gain transferable skills. The development and structure of a targeted professional development event, the New Librarians’ Symposium, is discussed. This successful event, held in Australia biennially, could be considered a model of targeted professional development for other professional associations and groups.
Publisher: Springer Science and Business Media LLC
Date: 06-10-2020
DOI: 10.1038/S41467-020-18873-Z
Abstract: Development of high throughput single-cell sequencing technologies has made it cost-effective to profile thousands of cells from erse s les containing multiple cell types. To study how these different cell types work together, here we develop NATMI (Network Analysis Toolkit for Multicellular Interactions). NATMI uses connectomeDB2020 (a database of 2293 manually curated ligand-receptor pairs with literature support) to predict and visualise cell-to-cell communication networks from single-cell (or bulk) expression data. Using multiple published single-cell datasets we demonstrate how NATMI can be used to identify (i) the cell-type pairs that are communicating the most (or most specifically) within a network, (ii) the most active (or specific) ligand-receptor pairs active within a network, (iii) putative highly-communicating cellular communities and (iv) differences in intercellular communication when profiling given cell types under different conditions. Furthermore, analysis of the Tabula Muris (organism-wide) atlas confirms our previous prediction that autocrine signalling is a major feature of cell-to-cell communication networks, while also revealing that hundreds of ligands and their cognate receptors are co-expressed in in idual cells suggesting a substantial potential for self-signalling.
Publisher: Zenodo
Date: 2015
Publisher: Zenodo
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 02-06-2020
DOI: 10.1186/S13059-020-02048-6
Abstract: Single-cell RNA sequencing has been widely adopted to estimate the cellular composition of heterogeneous tissues and obtain transcriptional profiles of in idual cells. Multiple approaches for optimal s le dissociation and storage of single cells have been proposed as have single-nuclei profiling methods. What has been lacking is a systematic comparison of their relative biases and benefits. Here, we compare gene expression and cellular composition of single-cell suspensions prepared from adult mouse kidney using two tissue dissociation protocols. For each s le, we also compare fresh cells to cryopreserved and methanol-fixed cells. Lastly, we compare this single-cell data to that generated using three single-nucleus RNA sequencing workflows. Our data confirms prior reports that digestion on ice avoids the stress response observed with 37 °C dissociation. It also reveals cell types more abundant either in the cold or warm dissociations that may represent populations that require gentler or harsher conditions to be released intact. For cell storage, cryopreservation of dissociated cells results in a major loss of epithelial cell types in contrast, methanol fixation maintains the cellular composition but suffers from ambient RNA leakage. Finally, cell type composition differences are observed between single-cell and single-nucleus RNA sequencing libraries. In particular, we note an underrepresentation of T, B, and NK lymphocytes in the single-nucleus libraries. Systematic comparison of recovered cell types and their transcriptional profiles across the workflows has highlighted protocol-specific biases and thus enables researchers starting single-cell experiments to make an informed choice.
Publisher: Cold Spring Harbor Laboratory
Date: 14-07-2017
DOI: 10.1101/163519
Abstract: Macrophages are sentinel cells essential for tissue homeostasis and host defence. Owing to their plasticity, macrophages acquire a range of functional phenotypes in response to microenvironmental stimuli, of which M(IFN-γ) and M(IL-4/IL-13) are well-known for their opposing pro- and anti-inflammatory roles. Enhancers have emerged as regulatory DNA elements crucial for transcriptional activation of gene expression. Using cap analysis of gene expression and epigenetic data, we identify on large-scale transcribed enhancers in mouse macrophages, their time kinetics and target protein-coding genes. We observe an increase in target gene expression, concomitant with increasing numbers of associated enhancers and find that genes associated to many enhancers show a shift towards stronger enrichment for macrophage-specific biological processes. We infer enhancers that drive transcriptional responses of genes upon M(IFN-γ) and M(IL-4/IL-13) macrophage activation and demonstrate stimuli-specificity of regulatory associations. Finally, we show that enhancer regions are enriched for binding sites of inflammation-related transcription factors, suggesting a link between stimuli response and enhancer transcriptional control. Our study provides new insights into genome-wide enhancer-mediated transcriptional control of macrophage genes, including those implicated in macrophage activation, and offers a detailed genome-wide catalogue to further elucidate enhancer regulation in macrophages.
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1038/NATURE21374
Publisher: SAGE Publications
Date: 06-2016
Abstract: In September 2015, after more than three years of negotiations and intense involvement from many stakeholders, including the International Federation of Library Associations and Institutions (IFLA), the Member States of the United Nations adopted the post-2015 Development Agenda to succeed the Millennium Development Goals, Transforming Our World: The 2030 Agenda for Sustainable Development. This paper outlines and reflects on the key steps in IFLA’s c aign and the importance of coalitions and national advocacy to realise the inclusion of access to information, universal literacy, public access to information and communication technology, and cultural heritage in the UN 2030 Agenda.
Publisher: Cold Spring Harbor Laboratory
Date: 06-11-2019
DOI: 10.1101/832444
Abstract: Single-cell and single-nucleus RNA sequencing have been widely adopted in studies of heterogeneous tissues to estimate their cellular composition and obtain transcriptional profiles of in idual cells. However, the current fragmentary understanding of artefacts introduced by s le preparation protocols impedes the selection of optimal workflows and compromises data interpretation. To bridge this gap, we compared performance of several workflows applied to adult mouse kidneys. Our study encompasses two tissue dissociation protocols, two cell preservation methods, bulk tissue RNA sequencing, single-cell and three single-nucleus RNA sequencing workflows for the 10x Genomics Chromium platform. These experiments enable a systematic comparison of recovered cell types and their transcriptional profiles across the workflows and highlight protocol-specific biases important for the experimental design and data interpretation.
Publisher: Cold Spring Harbor Laboratory
Date: 29-08-2022
DOI: 10.1101/2022.08.29.505206
Abstract: High-grade serous ovarian carcinoma (HGSOC) is characterised by recurrence, chemotherapy resistance and overall poor prognosis. Genetic heterogeneity of tumour cells and the microenvironment of the tumour have been hypothesised as key determinants of treatment resistance and relapse. Here, using a combination of spatial and single cell transcriptomics (10x Visium and Chromium platforms), we examine tumour genetic heterogeneity and infiltrating populations of HGSOC s les from eight patients with variable response to neoadjuvant chemotherapy. By inferring gross copy number alterations (CNAs), we identified distinct tumour subclones co-existing within in idual tumour sections. These tumour subclones have unique CNA profiles and spatial locations within each tumour section, which were further validated by ultra-low-pass whole genome sequencing. Differential expression analysis between subclones within the same section identified both tumour cell intrinsic expression differences and markers indicative of different infiltrating cell populations. The gene sets differentially expressed between subclones were significantly enriched for genes encoding plasma membrane and secreted proteins, indicative of subclone-specific microenvironments. Furthermore, we identified tumour derived ligands with variable expression levels between subclones that correlated or anticorrelated with various non-malignant cell infiltration patterns. We highlight several of these that are potentially direct tumour-stroma/immune cell relationships as the non-malignant cell type expresses a cognate receptor for the tumour derived ligand. These include predictions of CXCL10-CXCR3 mediated recruitment of T and B cells to associate with the subclones of one patient and CD47-SIRPA mediated exclusion of macrophages from association with subclones of another. Finally, we show that published HGSOC molecular subtype signatures associated with prognosis are heterogeneously expressed across tumour sections and that areas containing different tumour subclones with different infiltration patterns can match different subtypes. Our study highlights the high degree of intratumoural subclonal and infiltrative heterogeneity in HGSOC which will be critical to better understand resistance and relapse.
Publisher: Zenodo
Date: 2019
Publisher: Cold Spring Harbor Laboratory
Date: 27-03-2022
DOI: 10.1101/2022.03.25.485695
Abstract: Current approaches to stage chronic liver diseases have limited utility to directly predict liver cancer risk. Here, we employed single nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and chronically injured pre-malignant livers using two distinct mouse models. Analysis of 40,748 hepatic nuclei unraveled a previously uncharacterized disease-associated hepatocyte transcriptional state (daHep). These cells were absent in healthy livers, but were increasingly prevalent as chronic liver disease progressed towards hepatocarcinogenesis. Gene expression deconvolution of 1,439 human liver transcriptomes from publicly available datasets revealed that daHep frequencies highly correlate with current histopathological liver disease staging systems. Importantly, we show that high daHep levels precede carcinogenesis in mice and humans and predict a higher risk of hepatocellular carcinoma (HCC) development. This novel transcriptional signature with diagnostic and, more importantly, prognostic significance has the potential to change the way chronic liver disease patients are staged, surveilled and risk-stratified.
Publisher: Informa UK Limited
Date: 2001
Publisher: WORLD SCIENTIFIC
Date: 2010
Publisher: Elsevier BV
Date: 05-2023
Publisher: Zenodo
Date: 2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-09-2023
Publisher: Open Science Framework
Date: 2020
Location: Australia
Location: Netherlands
Location: United Kingdom of Great Britain and Northern Ireland
Location: No location found
Location: New Zealand
Start Date: 2013
End Date: 2016
Funder: Bill and Melinda Gates Foundation
View Funded ActivityStart Date: 2014
End Date: 2018
Funder: Bill and Melinda Gates Foundation
View Funded ActivityStart Date: 2016
End Date: 2026
Funder: Bill and Melinda Gates Foundation
View Funded ActivityStart Date: 2009
End Date: 2012
Funder: Bill and Melinda Gates Foundation
View Funded Activity