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Cell-ECM Graphs: A Graph-Based Method for Joint Analysis of Cells and the Extracellular Matrix

Ghafoor, M.; Parkinson, J. E.; Sutherland, T. E.; Rattray, M.

2025-08-25 bioinformatics
10.1101/2025.06.04.657781 bioRxiv
Show abstract

Spatial proteomics technologies enable in situ characterization of both cells and the extracellular matrix (ECM), yet methods to jointly analyse their interactions remain limited. Here, we present a computational framework for constructing Cell-ECM graphs from spatial proteomics data, representing cells and ECM clusters as vertices and encoding cell-cell, ECM-ECM, and cell-ECM interactions as edges within a unified graph. This framework enables the application of established graph analytical methods to matrix biology, including node classification, unsupervised niche discovery, interaction analysis and whole-graph classification with explainable graph neural networks. Using both synthetic and real data, we show that Cell-ECM graphs capture alterations in ECM and cell-ECM interactions that are not resolved by traditional cell-only graphs. To promote accessibility and reproducibility, we provide an open-source Python package implementing the method, enabling its broad application to spatial proteomics studies of the ECM.

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