Biology subjects

Moore, J. W.

Publications and source records attributed to Moore, J. W..

11 recordsLinked to original sources

bioRxiv2026

netPCF: Geometry-Aware Pair Correlation Functions for Spatial Biology

Spatial organisation is a defining feature of biological systems, underpinning cellular interactions, tissue function, disease progression and therapeutic response. Identifying and quantifying spatial organisation may require methods that resolve relationships across spatial scales. The pair correlation function (PCF) quantifies spatial dependence between points across multiple length scales, but its standard Euclidean formulation is poorly suited to data defined on irregular, curved or otherwise structured domains, where tissue geometry may constrain biological organisation and distort Euclidean distances. Here, we introduce netPCF, a geometry-aware extension of the PCF for quantifying spatial organisation on complex biological domains. By representing tissue structures, anatomical surfaces and other constrained geometries as spatial networks, netPCF generalises the PCF beyond extrinsic Euclidean settings. The framework derives the expected behaviour of the statistic under complete spatial randomness using interpretable finite-support kernels, provides bootstrap-based uncertainty quantification, and includes practical criteria for assessing domain discretisation adequacy. We further extend netPCF to marked (labelled) biological data using feature kernels for categorical and continuous attributes, enabling unified analysis of cell identities, marker intensities, phenotypic states, gene expression and other quantitative features on structured domains in any spatial dimension. All methods are implemented in the open-source Python package spacenet. Synthetic studies show that netPCF recovers classical Euclidean behaviour on sufficiently resolved networks and is robust to common imaging noise. We demonstrate its utility in two biological applications. In three-dimensional imaging mass cytometry data from HER2+ breast carcinoma, netPCF separates tissue architecture-driven proximity from biologically meaningful endothelial and immune cell organisation. In reconstructed surfaces of developing murine embryos, netPCF identifies a transition in the Wnt1 -Wnt6 relationship from short-range co-localisation at E9.5 to spatial exclusion at E11.5, a pattern of ectodermal boundary refinement not captured by prior voxel-wise co-expression analysis. Overall, netPCF provides a statistically grounded and practical framework for quantifying spatial organisation on complex biological domains. Author summarySpatial organisation is central to many biological processes, but it is often measured using distances that ignore the shape of the tissue or structure being studied. We introduce netPCF, a method for quantifying multiscale spatial correlation in data that lie on complex biological domains, including irregular, curved, or branching structures. netPCF reconstructs the domain as a distance-preserving spatial network and estimates pair correlation along this intrinsic geometry, allowing spatial associations to be interpreted relative to the structure in which they occur. The framework includes uncertainty estimates and extensions for categorical and continuous markers, supporting analysis of cell types, marker intensities, phenotypic states, and gene expression patterns. In synthetic data, netPCF recovers expected spatial behaviour on well-resolved networks. In biological imaging data, it distinguishes apparent cell proximity caused by breast carcinoma tissue architecture from biologically meaningful cell organisation, and reveals a developmental transition in Wnt gene organisation over the surface of a murine embryo that direct co-expression analysis does not capture. netPCF is available in the open-source Python package spacenet, supplemented with online tutorials supporting practical use across spatial biology applications.

bioinformatics↗

bioRxiv2026

Stromal Prostaglandin is a Dominant Spatial Regulator of Cell-fate Plasticity in Colorectal Cancer

Colorectal cancer (CRC) tumours with high stromal content have a worse outcome, but the mechanisms governing this are unclear. Using high-throughput single-cell perturbation analysis of CRC patient-derived organoids (PDOs) and cancer-associated fibroblasts (CAFs) we find that epithelial cells with high stromal-communication potential are marked by the transcriptional co-repressor DACH1. To define the causal regulators of stromal-epithelial signalling, we developed a novel CRISPR screening platform to perturb the CAF secretome and measure epithelial stem cell responses at single-cell resolution. Intercellular CRISPR screening and full factorial ligand analysis revealed that stromal Prostaglandin E2 (PGE2) is a dominant regulator of CRC cell-fate plasticity. Stromal PGE2 converts DACH1+ epithelia from a chemosensitive proliferative colonic stem cell (proCSC) fate into a chemorefractory and prometastatic revival colonic stem cell (revCSC) fate. PGE2-driven epithelial transdetermination is rapid and reversible, providing an acute mechanism for stromal-driven plasticity in CRC tumours. Genetic and pharmacological inhibition of stromal COX2 inhibits epithelial plasticity, trapping CRC epithelia in an anti-metastatic and chemosensitive proCSC fate. PTGS2+ CAFs support a spatially resolved revCSC to proCSC plasticity gradient in human CRC tumours marked by increasing DACH1 expression. These results reveal that stromal prostaglandin is a dominant spatial regulator of poor-prognosis cell-fates and may explain the benefit of anti-COX therapies in both preventing and treating CRC.

cancer biology↗

bioRxiv2026

Quantifying Exposure of Pacific Salmon and Steelhead to Climate Change in the Fraser River basin

Climate change can affect salmon and steelhead (Oncorhynchus spp.) throughout their anadromous life cycles, yet there have been no assessments of which Canadian populations face the greatest exposure. We developed a framework to quantify relative climate change exposure of salmon and steelhead populations based on the spatial and temporal distribution of different life stages. Exposure was calculated from climate model projections for freshwater and marine climate variables considering unique impact thresholds for each population and life stage. We applied this framework to 60 Conservation Units of Pacific salmon and steelhead in the Fraser River basin, British Columbia. Lake-type sockeye had the highest exposure, driven by elevated stream temperatures during adult freshwater migration and spawning stages and relatively low thermal tolerance of marine stages. Chinook salmon were the next most exposed, while coho, pink, and chum salmon had relatively low exposure. Uniquely, steelhead exposure was driven by high stream temperatures during incubation. Our framework is broadly applicable, and our findings provide critical input for climate change vulnerability assessments and forward-looking resilience planning for Pacific salmon.

ecology↗

bioRxiv2025

Extracellular matrix viscoelasticity regulates mammary branching morphogenesis

Structural and mechanical cues from the extracellular matrix (ECM) regulate tissue morphogenesis. Tissue development has conventionally been studied with ex vivo systems where mechanical properties of the extracellular environment are either poorly controlled in space and time, lack tunability, or do not mimic ECM mechanics. For these reasons, it remains unknown how matrix stress relaxation rate, a time-dependent mechanical property that influences several cellular processes, regulates mammary branching morphogenesis. Here, we systematically investigated the influence of matrix stress relaxation on mammary branching morphogenesis using 3D alginate-collagen matrices and spheroids of human mammary epithelial cells. Slow stress relaxing matrices promoted significantly greater branch formation compared to fast stress relaxing matrices. Branching in slow stress relaxing matrices was accompanied by local collagen fiber alignment, while collagen fibers remained randomly oriented in fast stress relaxing matrices. In slow stress relaxing matrices, branch formation was driven by intermittent pulling contractions applied to the local ECM at the tips of elongating branches, which was accompanied by an abundance of phosphorylated focal adhesion kinase (phospho-FAK) and {beta}1 integrin at the tips of branches. On the contrary, we observed that growing spheroids in fast stress relaxing matrices applied isotropic pushing forces to the ECM. Pharmacological inhibition of both Rac1 and non-muscle myosin II prevented epithelial branch formation, regardless of matrix stress relaxation rate. Interestingly, restricting cellular expansion via increased osmotic pressure was sufficient to impede epithelial branching in slow stress relaxing matrices. This work highlights the importance of stress relaxation in regulating and directing mammary branch elongation.

bioengineering↗

bioRxiv2024

MuSpAn: A Toolbox for Multiscale Spatial Analysis

Advances in multiplex imaging and spatial omics have revolutionised spatial data generation in biology, revealing complex tissue organisation across multiple scales. However, methods for analysing these data have lagged behind, with fragmented, study-specific pipelines and limited guidance for tool selection. To address this, we introduce MuSpAn, a Multiscale Spatial Analysis package offering intuitive, flexible access to a wide range of mathematical tools - including spatial statistics, topological data analysis, geometry, and networks - within a unified framework. MuSpAn supports efficient data querying, is agnostic to imaging modality, and provides extensive documentation and community support. It enables users to create custom pipelines or conduct unbiased exploratory analyses. We demonstrate MuSpAns capacity to interrogate cross-compartmental cell interactions at multiple length scales in both normal and neoplastic tissue using mouse intestinal spatial transcriptomic datasets. Applied to a CMS4-like murine intestinal cancer model, MuSpAn identifies a continuum of fibroblastic functional phenotypes associated with discrete and coordinated fibroblast-immune interactions, highlighting its utility as a discovery tool across diverse biological contexts.

cell biology↗

bioRxiv2024

Integrating diverse statistical methods to analyse stage-discriminatory cell interactions in colorectal neoplasia

Spatial biology has the potential to unlock information about the disrupted cellular ecosystems that define human disease. Quantitative analysis of spatially-resolved cell interactions allows mapping of tissue self-organisation and assessment of why cells interact differently in physiological and pathological contexts. However, the complexity of mammalian tissues, that occur across a spectrum of length scales, presents significant challenges for spatial analysis, increasing the gap between our capacity to generate and biologically interpret these datasets. Here, we have adapted a range of mathematical tools to develop a suite of spatial descriptors, and deployed them to determine how cell interactions change as colorectal cancer progresses from benign precursors. We demonstrate that combining mathematical analyses permits insightful examination of tissue organisational structures and identifies variable cell-interaction pathways that underpin disease progression. Mathematical tool triangulation can cross-corroborate spatial biology findings, facilitating development of analysis pipelines that are robust to individual method limitations.

cancer biology↗

bioRxiv2023

Gradient organisation of functional connectivity within resting state networks is present from 25 weeks gestation in the human fetal brain

During the third trimester of human gestation, the structure and function of the fetal brain is developing rapidly, laying the foundation for its connectivity framework across the lifespan. During this juncture, resting state functional MRI can be used to identify resting state networks (RSNs) which mature across gestation to resemble canonical RSNs at full term. However, the emergence of finer grain organisation of connectivity within these RSNs in the fetal brain is unknown. Using in-utero resting state fMRI, we performed connectopic mapping analysis to explore the presence of gradients in functional connectivity organisation of 11 cortical RSNs, known as connectopic maps in fetuses aged 25-37 weeks gestation (GW). We hypothesised that, if present, development of connectopic maps would be network specific in the third trimester of gestation, such that this property would be present within the earlier maturing primary sensory and motor networks before those associated with higher association function. In keeping with this, we found smooth connectopic maps in all of the studied RSNs from 25 GW, with the most spatially consistency across gestational age in the primary sensory and motor networks. Voxel-wise permutation testing of the connectopic maps identified local clusters of voxels within networks that significantly covaried with age, specifically in multisensory processing areas, suggesting multisensory processing may be developing during this period. Our analysis shows that functional gradient organisation is already established in the fetal brain and develops throughout gestation, which has strong implications for understanding how cortical organisation subserves the emergence of behaviour in the ensuing period.

neuroscience↗

bioRxiv2022

The medial entorhinal cortex is necessary for the stimulus control over hippocampal place fields by distal, but not proximal, landmarks

A fundamental property of place cells in the hippocampus is the anchoring of their firing fields to salient landmarks within the environment. However, it is unclear how such information reaches the hippocampus. In the current experiment, we tested the hypothesis that the stimulus control exerted by distal visual landmarks requires input from the medial entorhinal cortex (MEC). Place cells were recorded from mice with ibotenic acid lesions of the MEC (n = 7) and from sham-lesioned mice (n = 6) following 90{degrees} rotations of either distal landmarks or proximal cues in a cue controlled environment. We found that lesions of the MEC impaired the anchoring of place fields to distal landmarks, but not proximal cues. We also observed that, relative to sham-lesioned mice, place cells in animals with MEC lesions exhibited significantly reduced spatial information and increased sparsity. These results support the view that distal landmark information reaches the hippocampus via the MEC, but that proximal cue information can do so via an alternative neural pathway.

neuroscience↗

bioRxiv2021

Linking habitat and population dynamics to inform conservation benchmarks for data-limited salmon stocks

Management of data-limited populations is a key challenge to the sustainability of fisheries around the world. For example, sockeye salmon (Oncorhynchus nerka) spawn and rear in many remote coastal watersheds of British Columbia (BC), Canada, making population assessment a challenge. Estimating conservation and management targets for these populations is particularly relevant given their importance to First Nations and commercial fisheries. Most sockeye salmon have obligate lake-rearing as juveniles, and total abundance is typically limited by production in rearing lakes. Although methods have been developed to estimate population capacity based on nursery lake photosynthetic rate (PR) and lake area or volume, they have not yet been widely incorporated into stock-recruit analyses. We tested the value of combining lake-based capacity estimates with traditional stock-recruit based approaches to assess population status using a hierarchical-Bayesian stock-recruit model for 70 populations across coastal BC. This analysis revealed regional variation in sockeye population productivity (Ricker ), with coastal stocks exhibiting lower mean productivity than those in interior watersheds. Using moderately-informative PR estimates of capacity as priors reduced model uncertainty, with a more than five-fold reduction in credible interval width for estimates of conservation benchmarks (e.g. SMAX - spawner abundance at carrying capacity). We estimated that almost half of these remote sockeye stocks are below one commonly applied conservation benchmarks (SMSY), despite substantial reductions in fishing pressure in recent decades. Thus, habitat-based capacity estimates can dramatically reduce scientific uncertainty in model estimates of management targets that underpin sustainable sockeye fisheries. More generally, our analysis reveals opportunities to integrate spatial analyses of habitat characteristics with population models to inform conservation and management of exploited species where population data are limited.

ecology↗

bioRxiv2020

Prioritizing conservation actions for Pacific salmon in Canada

O_LICurrent investment in conservation is insufficient to adequately protect and recover all ecosystems and species. The challenge of allocating limited funds is acute for Pacific salmon (Oncorhynchus spp.) in Canada, which lack a strategic approach to ensure that resources are spent on actions that would cost-effectively recover diminished populations. C_LIO_LIWe applied the Priority Threat Management framework to prioritize strategies that are most likely to maximize the number of thriving Pacific salmon populations on the Central Coast of British Columbia, Canada. These included 79 genetically, ecologically and spatially distinct population groups called Conservation Units (CUs) for five salmon species. This region has high salmon biodiversity and spans the territories of four First Nations: the Heiltsuk, Nuxalk, Kitasoo/Xaixais and Wuikinuxv. C_LIO_LIUsing structured expert elicitation of Indigenous and other experts, we quantified the estimated benefits, costs and feasibility of implementing 10 strategies. Under a business-as-usual scenario (i.e., no additional investments in salmon conservation or management), experts predicted that only one in four CUs would have >50% chance of achieving a thriving status within 20 years. Limiting future industrial development, which was predicted to safeguard CUs from future declines, was identified as the most cost-effective strategy. Investment in three strategies: 1) removal of artificial barriers to fish migration, 2) watershed protection, and 3) stream restoration - at 11.3M CAD per year - was predicted to result in nearly half (34 of 79) of the CUs having a >60% chance of meeting the conservation objective. C_LIO_LIIf all conservation strategies were implemented, experts estimated a >50% probability of achieving a thriving status for 78 of 79 CUs, at an annual cost of 17.3M CAD. However, even with the implementation of all strategies, most sockeye salmon CUs were unlikely to achieve higher probability targets of reaching the objective. C_LIO_LIPolicy implications: We illustrate how Priority Threat Management can incorporate the perspectives and expertise of Indigenous peoples and other experts to evaluate and prioritize conservation strategies based on their cost, benefit and feasibility. Timely investment in the strategies outlined in this assessment could help safeguard and recover Pacific salmon in this region of Canada. C_LI

ecology↗

bioRxiv2017

Eco-evolutionary dynamics and collective dispersal: implications for salmon metapopulation robustness

The spatial dispersal of individuals is known to play an important role in the dynamics of populations, and is central to metapopulation theory. At the same time, local adaptation to environmental conditions creates a geographic mosaic of evolutionary forces, where the combined drivers of selection and gene flow interact. Although the dispersal of individuals from donor to recipient populations provides connections within the metapopulation, promoting demographic and evolutionary rescue, it may also introduce maladapted individuals into habitats host to different environmental conditions, potentially lowering the fitness of the recipient population. Thus, dispersal plays a dual role in both promoting and inhibiting local adaptation. Here we explore a model of the eco-evolutionary dynamics between two populations connected by dispersal, where the productivity of each is defined by a trait complex that is subject to local selection. Although general in nature, our model is inspired by salmon metapopulations, where dispersal between populations is defined in terms of the straying rate, which has been shown to be density-dependent, and recently proposed to be shaped by social interactions consistent with collective movement. The results of our model reveal that increased straying between evolving populations leads to alternative stable states, which has large and nonlinear effects on two measures of metapopulation robustness: the portfolio effect and the time to recovery following an induced disturbance. We show that intermediate levels of straying result in large gains in robustness, and that increased habitat heterogeneity promotes robustness when straying rates are low, and erodes robustness when straying rates are high. Finally, we show that density-dependent straying promotes robustness, particularly when the aggregate biomass is low and straying is correspondingly high, which has important ramifications for the conservation of salmon metapopulations facing both natural and anthropogenic disturbances.\n\nMedia SummaryMany migratory species, such as salmon, are remarkable in finding their way home. This homing has allowed fine-scale adaptations to the environments in which they evolve. But some individuals do not find their way home and instead stray to other locations, especially when there are fewer individuals to help with collective decision-making. With an eco-evolutionary model, we discovered that an intermediate and density-dependent straying rate allows linked populations to be robust to disturbance but maintain local adaptations.

ecology↗