stClinic dissects clinically relevant niches by integrating spatial multi-slice multi-omics data in dynamic graphs

Chunman Zuo (), Junjie Xia, Yupeng Xu, Ying Xu, Pingting Gao, Jing Zhang, Yan Wang and Luonan Chen ()
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Chunman Zuo: Sun Yat-sen University
Junjie Xia: Donghua University
Yupeng Xu: Donghua University
Ying Xu: Southern University of Science and Technology
Pingting Gao: Fudan University
Jing Zhang: Secondary Military Medical University
Yan Wang: Jilin University
Luonan Chen: Shanghai Jiao Tong University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Spatial multi-slice multi-omics (SMSMO) integration has transformed our understanding of cellular niches, particularly in tumors. However, challenges like data scale and diversity, disease heterogeneity, and limited sample population size, impede the derivation of clinical insights. Here, we propose stClinic, a dynamic graph model that integrates SMSMO and phenotype data to uncover clinically relevant niches. stClinic aggregates information from evolving neighboring nodes with similar-profiles across slices, aided by a Mixture-of-Gaussians prior on latent features. Furthermore, stClinic directly links niches to clinical manifestations by characterizing each slice with attention-based geometric statistical measures, relative to the population. In cancer studies, stClinic uses survival time to assess niche malignancy, identifying aggressive niches enriched with tumor-associated macrophages, alongside favorable prognostic niches abundant in B and plasma cells. Additionally, stClinic identifies a niche abundant in SPP1+ MTRNR2L12+ myeloid cells and cancer-associated fibroblasts driving colorectal cancer cell adaptation and invasion in healthy liver tissue. These findings are supported by independent functional and clinical data. Notably, stClinic excels in label annotation through zero-shot learning and facilitates multi-omics integration by relying on other tools for latent feature initialization.

Date: 2025
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DOI: 10.1038/s41467-025-60575-x

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