School of Mathematics and Statistics - Research Publications
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ItemNo Preview AvailableMetaphor-A workflow for streamlined assembly and binning of metagenomes.(Oxford University Press (OUP), 2022-12-28)Recent advances in bioinformatics and high-throughput sequencing have enabled the large-scale recovery of genomes from metagenomes. This has the potential to bring important insights as researchers can bypass cultivation and analyze genomes sourced directly from environmental samples. There are, however, technical challenges associated with this process, most notably the complexity of computational workflows required to process metagenomic data, which include dozens of bioinformatics software tools, each with their own set of customizable parameters that affect the final output of the workflow. At the core of these workflows are the processes of assembly-combining the short-input reads into longer, contiguous fragments (contigs)-and binning, clustering these contigs into individual genome bins. The limitations of assembly and binning algorithms also pose different challenges depending on the selected strategy to execute them. Both of these processes can be done for each sample separately or by pooling together multiple samples to leverage information from a combination of samples. Here we present Metaphor, a fully automated workflow for genome-resolved metagenomics (GRM). Metaphor differs from existing GRM workflows by offering flexible approaches for the assembly and binning of the input data and by combining multiple binning algorithms with a bin refinement step to achieve high-quality genome bins. Moreover, Metaphor generates reports to evaluate the performance of the workflow. We showcase the functionality of Metaphor on different synthetic datasets and the impact of available assembly and binning strategies on the final results.
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ItemPerceptions of rural high school teachers - on the frontline of youth suicide(WILEY, 2022-10)OBJECTIVE: This study aimed to investigate the perceptions and beliefs of rural high school teachers about student suicide completion in their school and their perceived self-efficacy in identification of suicidality in students (suicidal ideation, plans and behaviours). DESIGN: A cross-sectional survey methodology. SETTING: Gippsland and the Loddon Mallee regions of Victoria, Australia. PARTICIPANTS: Rural high school teachers. OUTCOME MEASURE: A survey that aimed to obtain participants' perceptions and self-reports about students who had died by suicide in their school within the last 5 years, their perceived self-efficacy in identifying suicidal students and barriers to helping students at risk. RESULTS: Two hundred and seventy-seven rural high school teachers participated and 86% reported that a student from their school had died by suicide within the last 5 years. Sixty-five per cent believed that more than one student had died by suicide and 70% perceived they were currently aware of students experiencing suicidality in their class. Receiving professional development about suicide and obtaining help from mental health clinicians predicted perceived self-efficacy in identification of suicidality in students. Participants perceived the barriers to help students at risk included insufficient numbers of school-based mental health professionals and community mental health services. CONCLUSIONS: Many rural high school teachers perceive they are at the front line of the youth suicide crisis due to unmet service need in youth mental ill health. Increased access to effective services immediately after teachers become aware of suicidality may assist in reducing youth suicide in rural areas.
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ItemAssessing the quality of offshore Binomial sampling biosecurity inspections using onshore inspections(WILEY, 2022-07)Introduction of pests and diseases through trade is one of the main socio-ecological challenges worldwide. Although Binomial sampling inspection at the border can reduce pest entry risk, it is common for consignments to fail inspection, wasting resources for both exporter and importer. Outsourcing the inspection to the exporting country could reduce the cost of inspection for both parties. However, there is then a need to assess the quality of the offshore inspection. In this paper, we develop an inverse method combining past inspection data on the pathway, an onshore inspection sample, and the Beta-Binomial model to infer the sample size of the offshore inspection. We illustrate the method on two case studies: the importation of live plants through germplasm into Australia and the importation of pelleted seeds in New Zealand. In these case studies, we found that detecting four to five infested units in a single onshore inspection was typically sufficient to significantly doubt the presence of a compliant offshore inspection. We also ran a simulation experiment to quantify the statistical power to reject or accept the presence of compliant offshore inspection in practice: In highly infested pathways, we could detect the absence of offshore inspections after inspecting five consignments onshore. Less infested pathways required inspecting 20 to 60 consignments onshore. Our study demonstrates that Binomial sampling onshore can be used to assess the quality of offshore inspections.
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ItemArthropods on imported plant products: Volumes predict general trends while contextual details enhance predictive power(WILEY, 2022-04)Agricultural biosecurity interventions are aimed at minimizing introductions of harmful non-native organisms to new areas via agricultural trade. To prioritize such interventions, historical data on interceptions have been used to elucidate which factors determine the likelihood that a particular import is carrying a harmful organism. Here we use an interception data set of arthropod contaminants recorded on plant imports arriving in South Africa from 2005 to 2019, comprising 13,566 samples inspected for arthropod contaminants, of which 4902 were positive for the presence of at least one arthropod. We tested 29 predictor variables that have previously been used to explain variation in rates of detection and three variables describing possible sources of additional variation and grouped these into six mutually exclusive "factor classes." We used boosted regression trees as a non-parametric stochastic machine-learning method to build models for each factor class and interactions between them. We explored the influence of these variables with data split either randomly or chronologically. While we identified some specific patterns that could be explained post-hoc by historical events, only inspected volumes were reliably correlated with detection of arthropod contaminants across the whole data set. However, inspected volumes could not predict future interceptions of arthropods, which instead relied on contextual factors such as country, crop or year of import. This suggests that, although certain factors may be important in certain circumstances or for particular crops or commodities, there is little general predictive power in the current data. Instead, an idiographic approach would be most beneficial in biosecurity to ascertain the details of why a particular pest arrived on a particular pathway and how it might move (and be stopped) in future.
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ItemSSNIP-seq: A simple and rapid method for isolation of single-sperm nucleic acid for high-throughput sequencing(PUBLIC LIBRARY SCIENCE, 2022-09-29)We developed a simple and reliable method for the isolation of haploid nuclei from fresh and frozen testes. The described protocol uses readily available reagents in combination with flow cytometry to separate haploid and diploid nuclei. The protocol can be completed within 1 hour and the resulting individual haploid nuclei have intact morphology. The isolated nuclei are suitable for library preparation for high-throughput DNA and RNA sequencing using bulk or single nuclei. The protocol was optimised with mouse testes and we anticipate that it can be applied for the isolation of mature sperm from other mammals including humans.
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ItemIdentification and Re-consent of Existing Cord Blood Donors for Creation of Induced Pluripotent Stem Cell Lines for Potential Clinical Applications(OXFORD UNIV PRESS, 2022-10-21)We aim to create a bank of clinical grade cord blood-derived induced pluripotent stem cell lines in order to facilitate clinical research leading to the development of new cellular therapies. Here we present a clear pathway toward the creation of such a resource, within a strong quality framework, and with the appropriate regulatory, government and ethics approvals, along with a dynamic follow-up and re-consent process of cord blood donors from the public BMDI Cord Blood Bank. Interrogation of the cord blood bank inventory and next generation sequencing was used to identify and confirm 18 donors with suitable HLA homozygous haplotypes. Regulatory challenges that may affect global acceptance of the cell lines, along with the quality standards required to operate as part of a global network, are being met by working in collaboration with bodies such as the International Stem Cell Banking Initiative (ISCBI) and the Global Alliance for iPSC Therapies (GAiT). Ethics approval was granted by an Institutional Human Research Ethics Committee, and government approval has been obtained to use banked cord blood for this purpose. New issues of whole-genome sequencing and the relevant donor safeguards and protections were considered with input from clinical genetics services, including the rights and information flow to donors, and commercialization aspects. The success of these processes has confirmed feasibility and utility of using banked cord blood to produce clinical-grade iPSC lines for potential cellular therapies.
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ItemPrevalence of failure of passive immunity transfer in Australian non-replacement dairy calves(WILEY, 2022-07)Failure of passive immunity transfer (FPIT) increases the risk of morbidity and mortality in dairy calves. The prevalence of FPIT in dairy calves has generally been reported to be high, with FPIT estimated to occur in 38%-42% of Australian dairy calves. However, the focus of previous studies has been on replacement heifer calves. Our aim was to assess the prevalence of FPIT in Victorian bobby calves (non-replacement dairy calves). We collected blood samples from 3608 bobby calves at three abattoirs at exsanguination, and measured serum total protein as an indicator of passive transfer. We found that 36% of bobby calves showed evidence of FPIT (serum total protein ≤52 g/L), and 50% of calves had poor or fair passive transfer (<58 g/L). When a subset of calves (from farms with more than five calves in the dataset) was analysed using a linear mixed model, Jersey calves and crossbred/other calves had an estimated 5.3 g/L and 5.1 g/L higher serum total protein concentration, respectively, than Holstein-Friesian calves (P < 0.001). Our results suggest that the prevalence of FPIT in bobby calves at abattoirs is similar to that reported in dairy heifer calves sampled on farms. A high prevalence of FPIT has implications for bobby calf morbidity and mortality, as well as calf viability and profitability for dairy-beef production.
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ItemHow often do cancer researchers make their data and code available and what factors are associated with sharing?(BMC, 2022-11-09)BACKGROUND: Various stakeholders are calling for increased availability of data and code from cancer research. However, it is unclear how commonly these products are shared, and what factors are associated with sharing. Our objective was to evaluate how frequently oncology researchers make data and code available and explore factors associated with sharing. METHODS: A cross-sectional analysis of a random sample of 306 cancer-related articles indexed in PubMed in 2019 which studied research subjects with a cancer diagnosis was performed. All articles were independently screened for eligibility by two authors. Outcomes of interest included the prevalence of affirmative sharing declarations and the rate with which declarations connected to data complying with key FAIR principles (e.g. posted to a recognised repository, assigned an identifier, data license outlined, non-proprietary formatting). We also investigated associations between sharing rates and several journal characteristics (e.g. sharing policies, publication models), study characteristics (e.g. cancer rarity, study design), open science practices (e.g. pre-registration, pre-printing) and subsequent citation rates between 2020 and 2021. RESULTS: One in five studies declared data were publicly available (59/306, 19%, 95% CI: 15-24%). However, when data availability was investigated this percentage dropped to 16% (49/306, 95% CI: 12-20%), and then to less than 1% (1/306, 95% CI: 0-2%) when data were checked for compliance with key FAIR principles. While only 4% of articles that used inferential statistics reported code to be available (10/274, 95% CI: 2-6%), the odds of reporting code to be available were 5.6 times higher for researchers who shared data. Compliance with mandatory data and code sharing policies was observed in 48% (14/29) and 0% (0/6) of articles, respectively. However, 88% of articles (45/51) included data availability statements when required. Policies that encouraged data sharing did not appear to be any more effective than not having a policy at all. The only factors associated with higher rates of data sharing were studying rare cancers and using publicly available data to complement original research. CONCLUSIONS: Data and code sharing in oncology occurs infrequently, and at a lower rate than would be expected given the prevalence of mandatory sharing policies. There is also a large gap between those declaring data to be available, and those archiving data in a way that facilitates its reuse. We encourage journals to actively check compliance with sharing policies, and researchers consult community-accepted guidelines when archiving the products of their research.
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ItemEstimating the Distribution of Japanese Encephalitis Vectors in Australia Using Ecological Niche Modelling(MDPI, 2022-12)Recent Japanese encephalitis virus (JEV) outbreaks in southeastern Australia have sparked interest into epidemiological factors surrounding the virus' novel emergence in this region. Here, the geographic distribution of mosquito species known to be competent JEV vectors in the country was estimated by combining known mosquito occurrences and ecological drivers of distribution to reveal insights into communities at highest risk of infectious disease transmission. Species distribution models predicted that Culex annulirostris and Culex sitiens presence was mostly likely along Australia's eastern and northern coastline, while Culex quinquefasciatus presence was estimated to be most likely near inland regions of southern Australia as well as coastal regions of Western Australia. While Culex annulirostris is considered the dominant JEV vector in Australia, our ecological niche models emphasise the need for further entomological surveillance and JEV research within Australia.
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ItemRandomized phase I trial of antigen- specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA plus rheumatoid arthritis(AMER SOC CLINICAL INVESTIGATION INC, 2022-10-24)BACKGROUNDAntigen-specific regulation of autoimmune disease is a major goal. In seropositive rheumatoid arthritis (RA), T cell help to autoreactive B cells matures the citrullinated (Cit) antigen-specific immune response, generating RA-specific V domain glycosylated anti-Cit protein antibodies (ACPA VDG) before arthritis onset. Low or escalating antigen administration under "sub-immunogenic" conditions favors tolerance. We explored safety, pharmacokinetics, and immunological and clinical effects of s.c. DEN-181, comprising liposomes encapsulating self-peptide collagen II259-273 (CII) and NF-κB inhibitor 1,25-dihydroxycholecalciferol.METHODSA double-blind, placebo-controlled, exploratory, single-ascending-dose, phase I trial assessed the impact of low, medium, and high DEN-181 doses on peripheral blood CII-specific and bystander Cit64vimentin59-71-specific (Cit-Vim-specific) autoreactive T cell responses, cytokines, and ACPA in 17 HLA-DRB1*04:01+ or *01:01+ ACPA+ RA patients on methotrexate.RESULTSDEN-181 was well tolerated. Relative to placebo and normalized to baseline values, Cit-Vim-specific T cells decreased in patients administered medium and high doses of DEN-181. Relative to placebo, percentage of CII-specific programmed cell death 1+ T cells increased within 28 days of DEN-181. Exploratory analysis in DEN-181-treated patients suggested improved RA disease activity was associated with expansion of CII-specific and Cit-Vim-specific T cells; reduction in ACPA VDG, memory B cells, and inflammatory myeloid populations; and enrichment in CCR7+ and naive T cells. Single-cell sequencing identified T cell transcripts associated with tolerogenic TCR signaling and exhaustion after low or medium doses of DEN-181.CONCLUSIONThe safety and immunomodulatory activity of low/medium DEN-181 doses provide rationale to further assess antigen-specific immunomodulatory therapy in ACPA+ RA.TRIAL REGISTRATIONAnzctr.org.au identifier ACTRN12617001482358, updated September 8, 2022.FUNDINGInnovative Medicines Initiative 2 Joint Undertaking (grant agreement 777357), supported by European Union's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations; Arthritis Queensland; National Health and Medical Research Council (NHMRC) Senior Research Fellowship; and NHMRC grant 2008287.