School of Mathematics and Statistics - Research Publications

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Now showing 1 - 10 of 1223
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    A spatio-temporal model of multi-marker antimalarial resistance
    Foo, YS ; Flegg, JA (ROYAL SOC, 2024-01-17)
    The emergence and spread of drug-resistant Plasmodium falciparum parasites have hindered efforts to eliminate malaria. Monitoring the spread of drug resistance is vital, as drug resistance can lead to widespread treatment failure. We develop a Bayesian model to produce spatio-temporal maps that depict the spread of drug resistance, and apply our methods for the antimalarial sulfadoxine-pyrimethamine. We infer from genetic count data the prevalences over space and time of various malaria parasite haplotypes associated with drug resistance. Previous work has focused on inferring the prevalence of individual molecular markers. In reality, combinations of mutations at multiple markers confer varying degrees of drug resistance to the parasite, indicating that multiple markers should be modelled together. However, the reporting of genetic count data is often inconsistent as some studies report haplotype counts, whereas some studies report mutation counts of individual markers separately. In response, we introduce a latent multinomial Gaussian process model to handle partially reported spatio-temporal count data. As drug-resistant mutations are often used as a proxy for treatment efficacy, point estimates from our spatio-temporal maps can help inform antimalarial drug policies, whereas the uncertainties from our maps can help with optimizing sampling strategies for future monitoring of drug resistance.
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    A multi-criteria framework for disease surveillance site selection: case study for Plasmodium knowlesi malaria in Indonesia
    Harrison, LE ; Flegg, JA ; Tobin, R ; Lubis, IND ; Noviyanti, R ; Grigg, MJ ; Shearer, FM ; Price, DJ (ROYAL SOC, 2024-01-10)
    Disease surveillance aims to collect data at different times or locations, to assist public health authorities to respond appropriately. Surveillance of the simian malaria parasite, Plasmodium knowlesi, is sparse in some endemic areas and the spatial extent of transmission is uncertain. Zoonotic transmission of Plasmodium knowlesi has been demonstrated throughout Southeast Asia and represents a major hurdle to regional malaria elimination efforts. Given an arbitrary spatial prediction of relative disease risk, we develop a flexible framework for surveillance site selection, drawing on principles from multi-criteria decision-making. To demonstrate the utility of our framework, we apply it to the case study of Plasmodium knowlesi malaria surveillance site selection in western Indonesia. We demonstrate how statistical predictions of relative disease risk can be quantitatively incorporated into public health decision-making, with specific application to active human surveillance of zoonotic malaria. This approach can be used in other contexts to extend the utility of modelling outputs.
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    Three-dimensional genome architecture coordinates key regulators of lineage specification in mammary epithelial cells
    Milevskiy, MJG ; Coughlan, HD ; Kane, SR ; Johanson, TM ; Kordafshari, S ; Chan, WF ; Tsai, M ; Surgenor, E ; Wilcox, S ; Allan, RS ; Chen, Y ; Lindeman, GJ ; Smyth, GK ; Visvader, JE (ELSEVIER, 2023-11-08)
    Although lineage-specific genes have been identified in the mammary gland, little is known about the contribution of the 3D genome organization to gene regulation in the epithelium. Here, we describe the chromatin landscape of the three major epithelial subsets through integration of long- and short-range chromatin interactions, accessibility, histone modifications, and gene expression. While basal genes display exquisite lineage specificity via distal enhancers, luminal-specific genes show widespread promoter priming in basal cells. Cell specificity in luminal progenitors is largely mediated through extensive chromatin interactions with super-enhancers in gene-body regions in addition to interactions with polycomb silencer elements. Moreover, lineage-specific transcription factors appear to be controlled through cell-specific chromatin interactivity. Finally, chromatin accessibility rather than interactivity emerged as a defining feature of the activation of quiescent basal stem cells. This work provides a comprehensive resource for understanding the role of higher-order chromatin interactions in cell-fate specification and differentiation in the adult mouse mammary gland.
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    NEARBY CYCLE SHEAVES FOR SYMMETRIC PAIRS
    Grinberg, M ; Vilonen, K ; Xue, T (JOHNS HOPKINS UNIV PRESS, 2023-02)
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    Rank 1 perturbations in random matrix theory - A review of exact results
    Forrester, PJ (WORLD SCIENTIFIC PUBL CO PTE LTD, 2023-10)
    A number of random matrix ensembles permitting exact determination of their eigenvalue and eigenvector statistics maintain this property under a rank [Formula: see text] perturbation. Considered in this review are the additive rank [Formula: see text] perturbation of the Hermitian Gaussian ensembles, the multiplicative rank [Formula: see text] perturbation of the Wishart ensembles, and rank [Formula: see text] perturbations of Hermitian and unitary matrices giving rise to a two-dimensional support for the eigenvalues. The focus throughout is on exact formulas, which are typically the result of various integrable structures. The simplest is that of a determinantal point process, with others relating to partial differential equations implied by a formulation in terms of certain random tridiagonal matrices. Attention is also given to eigenvector overlaps in the setting of a rank [Formula: see text] perturbation.
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    Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells.
    Park, SL ; Christo, SN ; Wells, AC ; Gandolfo, LC ; Zaid, A ; Alexandre, YO ; Burn, TN ; Schröder, J ; Collins, N ; Han, S-J ; Guillaume, SM ; Evrard, M ; Castellucci, C ; Davies, B ; Osman, M ; Obers, A ; McDonald, KM ; Wang, H ; Mueller, SN ; Kannourakis, G ; Berzins, SP ; Mielke, LA ; Carbone, FR ; Kallies, A ; Speed, TP ; Belkaid, Y ; Mackay, LK (American Association for the Advancement of Science (AAAS), 2023-12)
    Skin-resident CD8+ T cells include distinct interferon-γ-producing [tissue-resident memory T type 1 (TRM1)] and interleukin-17 (IL-17)-producing (TRM17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that TRM1 and TRM17 cells navigate divergent trajectories to acquire tissue residency in the skin. TRM1 cells depend on a T-bet-Hobit-IL-15 axis, whereas TRM17 cells develop independently of these factors. Instead, c-Maf commands a tissue-resident program in TRM17 cells parallel to that induced by Hobit in TRM1 cells, with an ICOS-c-Maf-IL-7 axis pivotal to TRM17 cell commitment. Accordingly, by targeting this pathway, skin TRM17 cells can be ablated without compromising their TRM1 counterparts. Thus, skin-resident T cells rely on distinct molecular circuitries, which can be exploited to strategically modulate local immunity.
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    Probing Hilbert space fragmentation and the block inverse participation ratio
    Frey, P ; Mikhail, D ; Rachel, S ; Hackl, L (American Physical Society (APS), 2024-02-01)
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    Point torque representations of ciliary flows
    Selvan, SA ; Duck, PW ; Pihler-Puzovic, D ; Brumley, DR (AMER PHYSICAL SOC, 2023-12-12)
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    Deformed Polynuclear Growth in (1 + 1) Dimensions
    Aggarwal, A ; Borodin, A ; Wheeler, M (Oxford University Press (OUP), 2023-03-01)
    Abstract We introduce and study a one parameter deformation of the polynuclear growth (PNG) in (1+1)-dimensions, which we call the $t$-PNG model. It is defined by requiring that, when two expanding islands merge, with probability $t$ they sprout another island on top of the merging location. At $t=0$, this becomes the standard (non-deformed) PNG model that, in the droplet geometry, can be reformulated through longest increasing subsequences of uniformly random permutations or through an algorithm known as patience sorting. In terms of the latter, the $t$-PNG model allows errors to occur in the sorting algorithm with probability $t$. We prove that the $t$-PNG model exhibits one-point Tracy–Widom Gaussian Unitary Ensemble asymptotics at large times for any fixed $t\in [0,1)$, and one-point convergence to the narrow wedge solution of the Kardar–Parisi–Zhang equation as $t$ tends to $1$. We further construct distributions for an external source that are likely to induce Baik–Ben Arous–Péché-type phase transitions. The proofs are based on solvable stochastic vertex models and their connection to the determinantal point processes arising from Schur measures on partitions.
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    Normal approximation in total variation for statistics in geometric probability
    Cong, T ; Xia, A (Cambridge University Press (CUP), 2024-03-03)
    Abstract We use Stein’s method to establish the rates of normal approximation in terms of the total variation distance for a large class of sums of score functions of samples arising from random events driven by a marked Poisson point process on $\mathbb{R}^d$ . As in the study under the weaker Kolmogorov distance, the score functions are assumed to satisfy stabilisation and moment conditions. At the cost of an additional non-singularity condition, we show that the rates are in line with those under the Kolmogorov distance. We demonstrate the use of the theorems in four applications: Voronoi tessellations, k-nearest-neighbours graphs, timber volume, and maximal layers.