arXiv subjects

Heather A. Harrington

Publications and source records attributed to Heather A. Harrington.

At least 37 records · Page 2Linked to original sources

arXiv2023

Zigzag persistence for coral reef resilience using a stochastic spatial model

A complex interplay between species governs the evolution of spatial patterns in ecology. An open problem in the biological sciences is characterising spatio-temporal data and understanding how changes at the local scale affect global dynamics/behaviour. Here, we extend a well-studied temporal mathematical model of coral reef dynamics to include stochastic and spatial interactions and generate data to study different ecological scenarios. We present descriptors to characterise patterns in heterogeneous spatio-temporal data surpassing spatially averaged measures. We apply these descriptors to simulated coral data and demonstrate the utility of two topological data analysis techniques--persistent homology and zigzag persistence--for characterising mechanisms of reef resilience. We show that the introduction of local competition between species leads to the appearance of coral clusters in the reef. We use our analyses to distinguish temporal dynamics stemming from different initial configurations of coral, showing that the neighbourhood composition of coral sites determines their long-term survival. Using zigzag persistence, we determine which spatial configurations protect coral from extinction in different environments. Finally, we apply this toolkit of multi-scale methods to empirical coral reef data, which distinguish spatio-temporal reef dynamics in different locations, and demonstrate the applicability to a range of datasets.

q-bio.QM↗

arXiv2023

Topological classification of tumour-immune interactions and dynamics

The complex and dynamic crosstalk between tumour and immune cells results in tumours that can exhibit distinct qualitative behaviours - elimination, equilibrium, and escape - and intricate spatial patterns, yet share similar cell configurations in the early stages. We offer a topological approach to analyse time series of spatial data of cell locations (including tumour cells and macrophages) in order to predict malignant behaviour. We propose four topological vectorisations specialised to such cell data: persistence images of Vietoris-Rips and radial filtrations at static time points, and persistence images for zigzag filtrations and persistence vineyards varying in time. To demonstrate the approach, synthetic data are generated from an agent-based model with varying parameters. We compare the performance of topological summaries in predicting - with logistic regression at various time steps - whether tumour niches surrounding blood vessels are present at the end of the simulation, as a proxy for metastasis (i.e., tumour escape). We find that both static and time-dependent methods accurately identify perivascular niche formation, significantly earlier than simpler markers such as the number of tumour cells and the macrophage phenotype ratio. We find additionally that dimension 0 persistence applied to macrophage data, representing multi-scale clusters of the spatial arrangement of macrophages, performs best at this classification task at early time steps, prior to full tumour development, and performs even better when time-dependent data are included; in contrast, topological measures capturing the shape of the tumour, such as tortuosity and punctures in the cell arrangement, perform best at intermediate and later stages. The logistic regression coefficients reveal detailed shape differences between the classes.

q-bio.CB↗

arXiv2022

Detecting Temporal shape changes with the Euler Characteristic Transform

Organoids are multi-cellular structures which are cultured in vitro from stem cells to resemble specific organs (e.g., brain, liver) in their three-dimensional composition. Dynamic changes in the shape and composition of these model systems can be used to understand the effect of mutations and treatments in health and disease. In this paper, we propose a new technique in the field of topological data analysis for DEtecting Temporal shape changes with the Euler Characteristic Transform (DETECT). DETECT is a rotationally invariant signature of dynamically changing shapes. We demonstrate our method on a data set of segmented videos of mouse small intestine organoid experiments and show that it outperforms classical shape descriptors. We verify our method on a synthetic organoid data set and illustrate how it generalises to 3D. We conclude that DETECT offers rigorous quantification of organoids and opens up computationally scalable methods for distinguishing different growth regimes and assessing treatment effects.

q-bio.QM↗

arXiv2022

Topological Data Analysis Detects Percolation Thresholds in Arctic Melt-Pond Evolution

During the summer melt period, ponds form on the surface of Arctic sea ice as it melts, with important consequences for ice evolution and marine ecology. Due to the ice-albedo feedback, these melt ponds experience uneven heat absorption, and exhibit complex patterns, which has motivated the development of modelling and data analysis to understand their particular dynamics. We provide a multiscale shape analysis using tools from computational algebraic topology, simultaneously capturing convexity, proximity, integrity, and feature size complementing existing single-scale quantification. Of particular interest in modelling the ponds is a percolation threshold at which local pond structure begins merging into macroscopic features. This percolation threshold has previously been observed using fractal dimension techniques. The signed Euclidean distance transform (SEDT) is a topological encoding of heterogeneous shape in binary images, and has been previously applied to porous media for percolation as well as other material behaviours. Here we adapt the SEDT for Arctic melt pond data to give a rich characterization and computation of shape, quantifying overall melt pond development in several complementary ways, and from which classical percolation and dimension results can be extracted. This orientation-invariant topological approach distinguishes different dynamical network models of melt pond evolution of varying complexity.

physics.data-an↗

arXiv2022

Multiscale topology classifies and quantifies cell types in subcellular spatial transcriptomics

Spatial transcriptomics has the potential to transform our understanding of RNA expression in tissues. Classical array-based technologies produce multiple-cell-scale measurements requiring deconvolution to recover single cell information. However, rapid advances in subcellular measurement of RNA expression at whole-transcriptome depth necessitate a fundamentally different approach. To integrate single-cell RNA-seq data with nanoscale spatial transcriptomics, we present a topological method for automatic cell type identification (TopACT). Unlike popular decomposition approaches to multicellular resolution data, TopACT is able to pinpoint the spatial locations of individual sparsely dispersed cells without prior knowledge of cell boundaries. Pairing TopACT with multiparameter persistent homology landscapes predicts immune cells forming a peripheral ring structure within kidney glomeruli in a murine model of lupus nephritis, which we experimentally validate with immunofluorescent imaging. The proposed topological data analysis unifies multiple biological scales, from subcellular gene expression to multicellular tissue organization.

q-bio.QM↗

arXiv2022

Algebraic network reconstruction of discrete dynamical systems

We present a computational algebra solution to reverse engineering the network structure of discrete dynamical systems from data. We use monomial ideals to determine dependencies between variables that encode constraints on the possible wiring diagrams underlying the process generating the discrete-time, continuous-space data. Our work assumes that each variable is either monotone increasing or decreasing. We prove that with enough data, even in the presence of small noise, our method can reconstruct the correct unique wiring diagram.

q-bio.QM↗

arXiv2022

Stability of topological descriptors for neuronal morphology

The topological morphology descriptor of a neuron is a multiset of intervals associated to the shape of the neuron represented as a tree. In practice, topological morphology descriptors are vectorized using persistence images, which can help classify and characterize the morphology of broad groups of neurons. We study the stability of topological morphology descriptors under small changes to neuronal morphology. We show that the persistence diagram arising from the topological morphology descriptor of a neuron is stable for the 1-Wasserstein distance against a range of perturbations to the tree. These results guarantee that persistence images of topological morphology descriptors are stable against the same set of perturbations and reliable.

q-bio.NC↗

arXiv2022

Grounded persistent path homology: a stable, topological descriptor for weighted digraphs

Weighted digraphs are used to model a variety of natural systems and can exhibit interesting structure across a range of scales. In order to understand and compare these systems, we require stable, interpretable, multiscale descriptors. To this end, we propose grounded persistent path homology (GrPPH) - a new, functorial, topological descriptor that describes the structure of an edge-weighted digraph via a persistence barcode. We show there is a choice of circuit basis for the graph which yields geometrically interpretable representatives for the features in the barcode. Moreover, we show the barcode is stable, in bottleneck distance, to both numerical and structural perturbations. GrPPH arises from a flexible framework, parametrised by a choice of digraph chain complex and a choice of filtration; for completeness, we also investigate replacing the path homology complex, used in GrPPH, by the directed flag complex.

math.AT↗

arXiv2022

Hypergraphs for multiscale cycles in structured data

Scientific data has been growing in both size and complexity across the modern physical, engineering, life and social sciences. Spatial structure, for example, is a hallmark of many of the most important real-world complex systems, but its analysis is fraught with statistical challenges. Topological data analysis can provide a powerful computational window on complex systems. Here we present a framework to extend and interpret persistent homology summaries to analyse spatial data across multiple scales. We introduce hyperTDA, a topological pipeline that unifies local (e.g. geodesic) and global (e.g. Euclidean) metrics without losing spatial information, even in the presence of noise. Homology generators offer an elegant and flexible description of spatial structures and can capture the information computed by persistent homology in an interpretable way. Here the information computed by persistent homology is transformed into a weighted hypergraph, where hyperedges correspond to homology generators. We consider different choices of generators (e.g. matroid or minimal) and find that centrality and community detection are robust to either choice. We compare hyperTDA to existing geometric measures and validate its robustness to noise. We demonstrate the power of computing higher-order topological structures on spatial curves arising frequently in ecology, biophysics, and biology, but also in high-dimensional financial datasets. We find that hyperTDA can select between synthetic trajectories from the landmark 2020 AnDi challenge and quantifies movements of different animal species, even when data is limited.

math.AT↗

arXiv2022

Multiscale methods for signal selection in single-cell data

Analysis of single-cell transcriptomics often relies on clustering cells and then performing differential gene expression (DGE) to identify genes that vary between these clusters. These discrete analyses successfully determine cell types and markers; however, continuous variation within and between cell types may not be detected. We propose three topologically motivated mathematical methods for unsupervised feature selection that consider discrete and continuous transcriptional patterns on an equal footing across multiple scales simultaneously. Eigenscores ($\text{eig}_i$) rank signals or genes based on their correspondence to low-frequency intrinsic patterning in the data using the spectral decomposition of the Laplacian graph. The multiscale Laplacian score (MLS) is an unsupervised method for locating relevant scales in data and selecting the genes that are coherently expressed at these respective scales. The persistent Rayleigh quotient (PRQ) takes data equipped with a filtration, allowing the separation of genes with different roles in a bifurcation process (e.g., pseudo-time). We demonstrate the utility of these techniques by applying them to published single-cell transcriptomics data sets. The methods validate previously identified genes and detect additional biologically meaningful genes with coherent expression patterns. By studying the interaction between gene signals and the geometry of the underlying space, the three methods give multidimensional rankings of the genes and visualisation of relationships between them.

q-bio.QM↗

arXiv2022

What are higher-order networks?

Network-based modeling of complex systems and data using the language of graphs has become an essential topic across a range of different disciplines. Arguably, this graph-based perspective derives its success from the relative simplicity of graphs: A graph consists of nothing more than a set of vertices and a set of edges, describing relationships between pairs of such vertices. This simple combinatorial structure makes graphs interpretable and flexible modeling tools. The simplicity of graphs as system models, however, has been scrutinized in the literature recently. Specifically, it has been argued from a variety of different angles that there is a need for higher-order networks, which go beyond the paradigm of modeling pairwise relationships, as encapsulated by graphs. In this survey article we take stock of these recent developments. Our goals are to clarify (i) what higher-order networks are, (ii) why these are interesting objects of study, and (iii) how they can be used in applications.

cs.SI↗

arXiv2022

Multiscale Topology Characterises Dynamic Tumour Vascular Networks

Advances in imaging techniques enable high resolution 3D visualisation of vascular networks over time and reveal abnormal structural features such as twists and loops, and their quantification is an active area of research. Here we showcase how topological data analysis (TDA), the mathematical field that studies `shape' of data, can characterise the geometric, spatial and temporal organisation of vascular networks. We propose two topological lenses to study vasculature, which capture inherent multi-scale features and vessel connectivity, and surpass the single scale analysis of existing methods. We analyse images collected using intravital and ultramicroscopy modalities and quantify spatio-temporal variation of twists, loops, and avascular regions (voids) in 3D vascular networks. This topological approach validates and quantifies known qualitative trends such as dynamic changes in tortuosity and loops in response to antibodies that modulate vessel sprouting; furthermore, it quantifies the effect of radiotherapy on vessel architecture.

q-bio.QM↗

arXiv2022

Barcodes distinguish morphology of neuronal tauopathy

The geometry of neurons is known to be important for their functions. Hence, neurons are often classified by their morphology. Two recent methods, persistent homology and the topological morphology descriptor, assign a morphology descriptor called a barcode to a neuron equipped with a given function, such as the Euclidean distance from the root of the neuron. These barcodes can be converted into matrices called persistence images, which can then be averaged across groups. We show that when the defining function is the path length from the root, both the topological morphology descriptor and persistent homology are equivalent. We further show that persistence images arising from the path length procedure provide an interpretable summary of neuronal morphology. We introduce {topological morphology functions}, a class of functions similar to Sholl functions, that can be recovered from the associated topological morphology descriptor. To demonstrate this topological approach, we compare healthy cortical and hippocampal mouse neurons to those affected by progressive tauopathy. We find a significant difference in the morphology of healthy neurons and those with a tauopathy at a postsymptomatic age. We use persistence images to conclude that the diseased group tends to have neurons with shorter branches as well as fewer branches far from the soma.

q-bio.NC↗

arXiv2022

Homology of homologous knotted proteins

Quantification and classification of protein structures, such as knotted proteins, often requires noise-free and complete data. Here we develop a mathematical pipeline that systematically analyzes protein structures. We showcase this geometric framework on proteins forming open-ended trefoil knots, and we demonstrate that the mathematical tool, persistent homology, faithfully represents their structural homology. This topological pipeline identifies important geometric features of protein entanglement and clusters the space of trefoil proteins according to their depth. Persistence landscapes quantify the topological difference between a family of knotted and unknotted proteins in the same structural homology class. This difference is localized and interpreted geometrically with recent advancements in systematic computation of homology generators. The topological and geometric quantification we find is robust to noisy input data, which demonstrates the potential of this approach in contexts where standard knot theoretic tools fail.

math.AT↗

arXiv2021

Algebra, Geometry and Topology of ERK Kinetics

The MEK/ERK signalling pathway is involved in cell division, cell specialisation, survival and cell death. Here we study a polynomial dynamical system describing the dynamics of MEK/ERK proposed by Yeung et al. with their experimental setup, data and known biological information. The experimental dataset is a time-course of ERK measurements in different phosphorylation states following activation of either wild-type MEK or MEK mutations associated with cancer or developmental defects. We demonstrate how methods from computational algebraic geometry, differential algebra, Bayesian statistics and computational algebraic topology can inform the model reduction, identification and parameter inference of MEK variants, respectively. Throughout, we show how this algebraic viewpoint offers a rigorous and systematic analysis of such models.

q-bio.QM↗

arXiv2021

Principal Components along Quiver Representations

Quiver representations arise naturally in many areas across mathematics. Here we describe an algorithm for calculating the vector space of sections, or compatible assignments of vectors to vertices, of any finite-dimensional representation of a finite quiver. Consequently, we are able to define and compute principal components with respect to quiver representations. These principal components are solutions to constrained optimisation problems defined over the space of sections, and are eigenvectors of an associated matrix pencil.

math.RT↗

arXiv2021

Topological Approximate Bayesian Computation for Parameter Inference of an Angiogenesis Model

Inferring the parameters of models describing biological systems is an important problem in the reverse engineering of the mechanisms underlying these systems. Much work has focused on parameter inference of stochastic and ordinary differential equation models using Approximate Bayesian Computation (ABC). While there is some recent work on inference in spatial models, this remains an open problem. Simultaneously, advances in topological data analysis (TDA), a field of computational mathematics, have enabled spatial patterns in data to be characterised. Here we focus on recent work using topological data analysis to study different regimes of parameter space for a well-studied model of angiogenesis. We propose a method for combining TDA with ABC to infer parameters in the Anderson-Chaplain model of angiogenesis. We demonstrate that this topological approach outperforms ABC approaches that use simpler statistics based on spatial features of the data. This is a first step towards a general framework of spatial parameter inference for biological systems, for which there may be a variety of filtrations, vectorisations, and summary statistics to be considered. All code used to produce our results is available as a Snakemake workflow.

q-bio.QM↗

arXiv2021

Topological data analysis distinguishes parameter regimes in the Anderson-Chaplain model of angiogenesis

Angiogenesis is the process by which blood vessels form from pre-existing vessels. It plays a key role in many biological processes, including embryonic development and wound healing, and contributes to many diseases including cancer and rheumatoid arthritis. The structure of the resulting vessel networks determines their ability to deliver nutrients and remove waste products from biological tissues. Here we simulate the Anderson-Chaplain model of angiogenesis at different parameter values and quantify the vessel architectures of the resulting synthetic data. Specifically, we propose a topological data analysis (TDA) pipeline for systematic analysis of the model. TDA is a vibrant and relatively new field of computational mathematics for studying the shape of data. We compute topological and standard descriptors of model simulations generated by different parameter values. We show that TDA of model simulation data stratifies parameter space into regions with similar vessel morphology. The methodologies proposed here are widely applicable to other synthetic and experimental data including wound healing, development, and plant biology.

q-bio.QM↗