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Catherine Higgins

Publications and source records attributed to Catherine Higgins.

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Statistical Analysis of Network Collections Using Persistent Homology and Functional Data Analysis

Statistical analysis of collections of networks, where each network is treated as the primary unit of observation, is of growing importance across a wide range of application domains, including gene regulatory, social, and financial networks. As networks consist of vertices and edges that do not naturally reside in Euclidean space, the direct application of conventional statistical methodologies, such as the computation of means and covariances, principal component analysis, and hypothesis testing, to samples of networks is not straightforward. A central challenge lies in defining meaningful measures of similarity or distance between networks of potentially varying sizes and structural types (e.g., directed, undirected, weighted or unweighted), particularly when no predefined node correspondence exists. To address these challenges, we introduce a framework termed functional topological data analysis (funTDA), which integrates tools from functional data analysis and topological data analysis to facilitate exploratory data analysis and inference on samples of networks. The proposed framework enables the computation of summary statistics, including means and variances, and supports the application of principal component analysis and hypothesis testing to topological features extracted from network data. Through simulation studies involving networks with varying connectivity structures, we demonstrate the ability of funTDA to distinguish between distinct network configurations. The methodology is illustrated through two real-data applications: networks constructed from pairwise word co-occurrences in novels by Jane Austen and Charles Dickens, and gene regulatory networks derived from gene expression measurements for seventeen individuals exposed to H3N2 influenza. In both applications, differences in network topology are assessed using principal component analysis and hypothesis testing.

stat.ME

Spatial Transcriptomics Iterative Hierarchical Clustering (stIHC): A Novel Method for Identifying Spatial Gene Co-Expression Modules

Recent advancements in spatial transcriptomics technologies allow researchers to simultaneously measure RNA expression levels for hundreds to thousands of genes while preserving spatial information within tissues, providing critical insights into spatial gene expression patterns, tissue organization, and gene functionality. However, existing methods for clustering spatially variable genes (SVGs) into co-expression modules often fail to detect rare or unique spatial expression patterns. To address this, we present spatial transcriptomics iterative hierarchical clustering (stIHC), a novel method for clustering SVGs into co-expression modules, representing groups of genes with shared spatial expression patterns. Through three simulations and applications to spatial transcriptomics datasets from technologies such as 10x Visium, 10x Xenium, and Spatial Transcriptomics, stIHC outperforms clustering approaches used by popular SVG detection methods, including SPARK, SPARK-X, MERINGUE, and SpatialDE. Gene Ontology enrichment analysis confirms that genes within each module share consistent biological functions, supporting the functional relevance of spatial co-expression. Robust across technologies with varying gene numbers and spatial resolution, stIHC provides a powerful tool for decoding the spatial organization of gene expression and the functional structure of complex tissues.

stat.ME