# stGCL: a versatile cross-modality fusion method based on multi-modal graph contrastive learning for spatial transcriptomics

**Authors:** Na Yu, Daoliang Zhang, Wei Zhang, Zhiping Liu, Xu Qiao, Chuanyuan Wang, Miaoqing Zhao, Weiming Yue, Wei Li, Yang De Marinis, Rui Gao

PMC · DOI: 10.1186/s13059-025-03896-w · 2026-01-28

## TL;DR

The paper introduces stGCL, a new method that combines different types of data from spatial transcriptomics to better understand tissue structure and function.

## Contribution

stGCL introduces a novel cross-modality fusion framework using graph contrastive learning for spatial transcriptomics data integration.

## Key findings

- stGCL reliably identifies spatial domains in tissue data.
- The method supports integration of vertical and horizontal tissue slices.
- stGCL is generalizable across different platforms and resolutions.

## Abstract

Advances in spatial transcriptomics have enabled high-resolution mapping of tissue architecture at the molecular level, yet integrating its multi-modal data remains challenging. Here, we present stGCL, a framework for accurate and robust integration of gene expression, spatial coordinates, and histological features. stGCL employs a histology-based Vision Transformer to extract morphological features and a multi-modal graph autoencoder with contrastive learning for cross-modal fusion. In addition, we introduce a spatial coordinate correction and registration strategy to support multi-slice integration. We demonstrate that stGCL reliably identifies spatial domains, integrates vertical and horizontal tissue slices, and highlight its generalizability across platforms and resolutions.

The online version contains supplementary material available at 10.1186/s13059-025-03896-w.

## Full-text entities

- **Genes:** AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}, Car3 (carbonic anhydrase 3) [NCBI Gene 12350] {aka Ca3, Car-3}, KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 17395] {aka B/MMP9, Clg4b, Gel B, MMP-9, pro-MMP-9}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, SFTPA2 (surfactant protein A2) [NCBI Gene 729238] {aka COLEC5, ILD2, PSAP, PSP-A, PSPA, SFTP1}, Lamp5 (lysosomal-associated membrane protein family, member 5) [NCBI Gene 76161] {aka 3110035N03Rik, 6330527O06Rik, BAD-LAMP, LAMP-5}, Car2 (carbonic anhydrase 2) [NCBI Gene 12349] {aka CAII, Ca2, Car-2, Ltw-5, Lvtw-5}, Prkcd (protein kinase C, delta) [NCBI Gene 18753] {aka D14Ertd420e, PKC[d], PKCdelta, Pkcd}, Mmp2 (matrix metallopeptidase 2) [NCBI Gene 17390] {aka Clg4a, GelA, MMP-2}, Vit (vitrin) [NCBI Gene 74199] {aka 1700052E02Rik, 1700110E08Rik, 2810429K11Rik, AKH, akhirin}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, Tff3 (trefoil factor 3, intestinal) [NCBI Gene 21786] {aka ITF, mITF}, Apoc1 (apolipoprotein C-I) [NCBI Gene 11812] {aka Apo-CIB, ApoC-IB, apo-CI, apoC-I}, Scgb3a1 (secretoglobin, family 3A, member 1) [NCBI Gene 68662] {aka HIN-1, LuLeu2, Pnsp2, UGRP2, Utgrp2}, WFDC2 (WAP four-disulfide core domain 2) [NCBI Gene 10406] {aka BENP, EDDM4, HE4, WAP5, dJ461P17.6}, AREG (amphiregulin) [NCBI Gene 374] {aka AR, AREGB, CRDGF, SDGF}, Gng4 (guanine nucleotide binding protein (G protein), gamma 4) [NCBI Gene 14706] {aka Hg3c}, Neurod6 (neurogenic differentiation 6) [NCBI Gene 11922] {aka Atoh2, Math-2, Math2, Nex, Nex1m, bHLHa2}, Gsta1 (glutathione S-transferase, alpha 1 (Ya)) [NCBI Gene 14857] {aka Gst2-1}, GPNMB (glycoprotein nmb) [NCBI Gene 10457] {aka HGFIN, NMB, PLCA3}, Igfbp2 (insulin-like growth factor binding protein 2) [NCBI Gene 16008] {aka IBP-2, Igfbp-2, mIGFBP-2}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, C1ql2 (complement component 1, q subcomponent-like 2) [NCBI Gene 226359] {aka Adii, CTRP10}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, SFTPA1 (surfactant protein A1) [NCBI Gene 653509] {aka COLEC4, ILD1, PSP-A, PSPA, SFTP1, SFTPA1B}, Car1 (carbonic anhydrase 1) [NCBI Gene 12346] {aka Ca1, Car-1}
- **Diseases:** DCIS (MESH:D002285), Cancer (MESH:D009369), lung cancer (MESH:D008175), PDAC (MESH:D021441), BA (MESH:D002282), NSCLC (MESH:D002289), Sigmoid (MESH:D012810), metastasis (MESH:D009362), invasive tumor (MESH:D009361), ST (MESH:D008569), breast cancer (MESH:D001943)
- **Chemicals:** H&amp;E (MESH:D006371), ARI (-), DAPI (MESH:C007293)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12924433/full.md

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Source: https://tomesphere.com/paper/PMC12924433