GASTON-Mix: a unified model of spatial gradients and domains using spatial mixture-of-experts.

Bioinformatics (Oxford, England)
Authors
Abstract

MOTIVATION: Gene expression varies across a tissue due to both the organization of the tissue into spatial domains, i.e. discrete regions of a tissue with distinct cell type composition, and continuous spatial gradients of gene expression within different spatial domains. Spatially resolved transcriptomics (SRT) technologies provide high-throughput measurements of gene expression in a tissue slice, enabling the characterization of spatial gradients and domains. However, existing computational methods for quantifying spatial variation in gene expression either model only spatial domains-and do not account for continuous gradients of expression-or require restrictive geometric assumptions on the spatial domains and spatial gradients that do not hold for many complex tissues.RESULTS: We introduce GASTON-Mix, a machine learning algorithm to identify both spatial domains and spatial gradients within each domain from SRT data. GASTON-Mix extends the mixture-of-experts (MoE) deep learning framework to a spatial MoE model, combining the clustering component of the MoE model with a neural field model that learns a separate 1D coordinate ("isodepth") within each domain. The spatial MoE is capable of representing any geometric arrangement of spatial domains in a tissue, and the isodepth coordinates define continuous gradients of gene expression within each domain. We show using simulations and real data that GASTON-Mix identifies spatial domains and spatial gradients of gene expression more accurately than existing methods. GASTON-Mix reveals spatial gradients in the striatum and lateral septum that regulate complex social behavior, and GASTON-Mix reveals localized spatial gradients of hypoxia and TNF-α signaling in the tumor microenvironment.AVAILABILITY AND IMPLEMENTATION: GASTON-Mix is available at .

Year of Publication
2025
Journal
Bioinformatics (Oxford, England)
Volume
41
Issue
Supplement_1
Pages
i523-i532
Date Published
07/2025
ISSN
1367-4811
DOI
10.1093/bioinformatics/btaf254
PubMed ID
40662777
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