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Main Authors: Long, Jiangkai, Zhu, Yanran, Tang, Chang, Sun, Kun, Liu, Yuanyuan, Yan, Xuesong
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2511.11380
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author Long, Jiangkai
Zhu, Yanran
Tang, Chang
Sun, Kun
Liu, Yuanyuan
Yan, Xuesong
author_facet Long, Jiangkai
Zhu, Yanran
Tang, Chang
Sun, Kun
Liu, Yuanyuan
Yan, Xuesong
contents Spatial transcriptomics enables gene expression profiling with spatial context, offering unprecedented insights into the tissue microenvironment. However, most computational models treat genes as isolated numerical features, ignoring the rich biological semantics encoded in their symbols. This prevents a truly deep understanding of critical biological characteristics. To overcome this limitation, we present SemST, a semantic-guided deep learning framework for spatial transcriptomics data clustering. SemST leverages Large Language Models (LLMs) to enable genes to "speak" through their symbolic meanings, transforming gene sets within each tissue spot into biologically informed embeddings. These embeddings are then fused with the spatial neighborhood relationships captured by Graph Neural Networks (GNNs), achieving a coherent integration of biological function and spatial structure. We further introduce the Fine-grained Semantic Modulation (FSM) module to optimally exploit these biological priors. The FSM module learns spot-specific affine transformations that empower the semantic embeddings to perform an element-wise calibration of the spatial features, thus dynamically injecting high-order biological knowledge into the spatial context. Extensive experiments on public spatial transcriptomics datasets show that SemST achieves state-of-the-art clustering performance. Crucially, the FSM module exhibits plug-and-play versatility, consistently improving the performance when integrated into other baseline methods.
format Preprint
id arxiv_https___arxiv_org_abs_2511_11380
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle When Genes Speak: A Semantic-Guided Framework for Spatially Resolved Transcriptomics Data Clustering
Long, Jiangkai
Zhu, Yanran
Tang, Chang
Sun, Kun
Liu, Yuanyuan
Yan, Xuesong
Machine Learning
Spatial transcriptomics enables gene expression profiling with spatial context, offering unprecedented insights into the tissue microenvironment. However, most computational models treat genes as isolated numerical features, ignoring the rich biological semantics encoded in their symbols. This prevents a truly deep understanding of critical biological characteristics. To overcome this limitation, we present SemST, a semantic-guided deep learning framework for spatial transcriptomics data clustering. SemST leverages Large Language Models (LLMs) to enable genes to "speak" through their symbolic meanings, transforming gene sets within each tissue spot into biologically informed embeddings. These embeddings are then fused with the spatial neighborhood relationships captured by Graph Neural Networks (GNNs), achieving a coherent integration of biological function and spatial structure. We further introduce the Fine-grained Semantic Modulation (FSM) module to optimally exploit these biological priors. The FSM module learns spot-specific affine transformations that empower the semantic embeddings to perform an element-wise calibration of the spatial features, thus dynamically injecting high-order biological knowledge into the spatial context. Extensive experiments on public spatial transcriptomics datasets show that SemST achieves state-of-the-art clustering performance. Crucially, the FSM module exhibits plug-and-play versatility, consistently improving the performance when integrated into other baseline methods.
title When Genes Speak: A Semantic-Guided Framework for Spatially Resolved Transcriptomics Data Clustering
topic Machine Learning
url https://arxiv.org/abs/2511.11380