arXiv subjects

Thomas E. Bartlett

Publications and source records attributed to Thomas E. Bartlett.

7 recordsLinked to original sources

arXiv2026

A Bayesian approach to model uncertainty in single-cell genomic data

Network models provide a powerful framework for analysing single-cell count data, facilitating the characterisation of cellular identities, disease mechanisms, and developmental trajectories. However, uncertainty modeling in unsupervised learning with genomic data remains insufficiently explored. Conventional clustering methods assign a singular identity to each cell, potentially obscuring transitional states during differentiation or mutation. This study introduces a variational Bayesian framework for clustering and analysing single-cell genomic data, employing a Bayesian Gaussian mixture model to estimate the probabilistic association of cells with distinct clusters. This approach captures cellular transitions, yielding biologically coherent insights into neurogenesis and breast cancer progression. The inferred clustering probabilities enable further analyses, including Differential Expression Analysis and pseudotime analysis. Furthermore, we propose utilising the misclustering rate and Area Under the Curve in clustering scRNA-seq data as an innovative metric to quantitatively evaluate overall clustering performance. This methodological advancement enhances the resolution of single-cell data analysis, enabling a more nuanced characterisation of dynamic cellular identities in development and disease.

q-bio.GN↗

arXiv2024

A stochastic network approach to clustering and visualising single-cell genomic count data

Important tasks in the study of genomic data include the identification of groups of similar cells (for example by clustering), and visualisation of data summaries (for example by dimensional reduction). In this paper, we develop a novel approach to these tasks in the context of single-cell genomic data. To do so, we propose to model the observed genomic data count matrix $\mathbf{X}\in\mathbb{Z}_{\geq0}^{p\times n}$, by representing these measurements as a bipartite network with multi-edges. Utilising this first-principles network model of the raw data, we cluster single cells in a suitably identified $d$-dimensional Laplacian Eigenspace (LE) via a Gaussian mixture model (GMM-LE), and employ UMAP to non-linearly project the LE to two dimensions for visualisation (UMAP-LE). This LE representation of the data-points estimates transformed latent positions (of genes and cells), under a latent position statistical model of nodes in a bipartite stochastic network. We demonstrate how transformations of these estimated latent positions can enable fine-grained clustering and visualisation of single-cell genomic data, by application to data from three recent genomics studies in different biological contexts. In each data application, clusters of cells independently learned by our proposed methodology are found to correspond to cells expressing specific marker genes that were independently defined by domain experts. In this validation setting, our proposed clustering methodology outperforms the industry-standard for these data. Furthermore, we validate components of the LE decomposition of the data by contrasting healthy cells from normal and at-risk groups in a machine-learning model, thereby identifying an LE cancer biomarker that significantly predicts long-term patient survival outcome in two independent validation cohorts with data from 1904 and 1091 individuals.

stat.ME↗

arXiv2021

Co-modularity and Detection of Co-communities

This paper introduces the notion of co-modularity, to co-cluster observations of bipartite networks into co-communities. The task of co-clustering is to group together nodes of one type with nodes of another type, according to the interactions that are the most similar. The novel measure of co-modularity is introduced to assess the strength of co-communities, as well as to arrange the representation of nodes and clusters for visualisation, and to define an objective function for optimisation. We demonstrate the usefulness of our proposed methodology on simulated data, and with examples from genomics and consumer-product reviews.

stat.ME↗

arXiv2020

Two-way sparsity for time-varying networks, with applications in genomics

We propose a novel way of modelling time-varying networks, by inducing two-way sparsity on local models of node connectivity. This two-way sparsity separately promotes sparsity across time and sparsity across variables (within time). Separation of these two types of sparsity is achieved through a novel prior structure, which draws on ideas from the Bayesian lasso and from copula modelling. We provide an efficient implementation of the proposed model via a Gibbs sampler, and we apply the model to data from neural development. In doing so, we demonstrate that the proposed model is able to identify changes in genomic network structure that match current biological knowledge. Such changes in genomic network structure can then be used by neuro-biologists to identify potential targets for further experimental investigation.

stat.ME↗

arXiv2016

Detection of Epigenomic Network Community Oncomarkers

In this paper we propose network methodology to infer prognostic cancer biomarkers based on the epigenetic pattern DNA methylation. Epigenetic processes such as DNA methylation reflect environmental risk factors, and are increasingly recognised for their fundamental role in diseases such as cancer. DNA methylation is a gene-regulatory pattern, and hence provides a means by which to assess genomic regulatory interactions. Network models are a natural way to represent and analyse groups of such interactions. The utility of network models also increases as the quantity of data and number of variables increase, making them increasingly relevant to large-scale genomic studies. We propose methodology to infer prognostic genomic networks from a DNA methylation-based measure of genomic interaction and association. We then show how to identify prognostic biomarkers from such networks, which we term `network community oncomarkers'. We illustrate the power of our proposed methodology in the context of a large publicly available breast cancer dataset.

stat.AP↗

arXiv2016

Network inference and community detection, based on covariance matrices, correlations and test statistics from arbitrary distributions

In this paper we propose methodology for inference of binary-valued adjacency matrices from various measures of the strength of association between pairs of network nodes, or more generally pairs of variables. This strength of association can be quantified by sample covariance and correlation matrices, and more generally by test-statistics and hypothesis test p-values from arbitrary distributions. Community detection methods such as block modelling typically require binary-valued adjacency matrices as a starting point. Hence, a main motivation for the methodology we propose is to obtain binary-valued adjacency matrices from such pairwise measures of strength of association between variables. The proposed methodology is applicable to large high-dimensional data-sets and is based on computationally efficient algorithms. We illustrate its utility in a range of contexts and data-sets.

stat.AP↗

arXiv2015

A Power Variance Test for Nonstationarity in Complex-Valued Signals

We propose a novel algorithm for testing the hypothesis of nonstationarity in complex-valued signals. The implementation uses both the bootstrap and the Fast Fourier Transform such that the algorithm can be efficiently implemented in O(NlogN) time, where N is the length of the observed signal. The test procedure examines the second-order structure and contrasts the observed power variance - i.e. the variability of the instantaneous variance over time - with the expected characteristics of stationary signals generated via the bootstrap method. Our algorithmic procedure is capable of learning different types of nonstationarity, such as jumps or strong sinusoidal components. We illustrate the utility of our test and algorithm through application to turbulent flow data from fluid dynamics.

stat.ME↗