arXiv subjects

Lewis Marsh

Publications and source records attributed to Lewis Marsh.

4 recordsLinked to original sources

arXiv2023

Stability and Inference of the Euler Characteristic Transform

The Euler characteristic transform (ECT) is a signature from topological data analysis (TDA) which summarises shapes embedded in Euclidean space. Compared with other TDA methods, the ECT is fast to compute and it is a sufficient statistic for a broad class of shapes. However, small perturbations of a shape can lead to large distortions in its ECT. In this paper, we propose a new metric on compact one-dimensional shapes and prove that the ECT is stable with respect to this metric. Crucially, our result uses curvature, rather than the size of a triangulation of an underlying shape, to control stability. We further construct a computationally tractable statistical estimator of the ECT based on the theory of Gaussian processes. We use our stability result to prove that our estimator is consistent on shapes perturbed by independent ambient noise; i.e., the estimator converges to the true ECT as the sample size increases.

math.ST↗

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

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↗

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↗