# Network models for bridging denoising and identifying spatial domains of spatially resolved transcriptomics

**Authors:** Haiyue Wang, Wensheng Zhang, Zaiyi Liu, Xiaoke Ma

PMC · DOI: 10.1371/journal.pcbi.1013867 · PLOS Computational Biology · 2026-01-13

## TL;DR

This paper introduces stACN, a new network model that improves the analysis of spatial transcriptomics data by jointly denoising and identifying spatial domains.

## Contribution

The novel contribution is stACN, an integrative network model that combines denoising and spatial domain identification in spatial transcriptomics.

## Key findings

- stACN improves data quality and spatial domain analysis in SRT datasets.
- The model effectively identifies domain-specific gene markers and generalizes well across datasets.

## Abstract

Spatially resolved transcriptomics (SRT) enables the simultaneous capture of gene expression profiles and spatial localization, providing valuable insights into tissue architecture. However, the preservation of spatial information requires additional experimental procedures, which often introduce substantial technical noise. Existing methods typically perform denoising and spatial domain identification in separate steps, leading to suboptimal performance and limiting their applicability. To address this limitation, we propose an integrative network model, stACN ( spatial transcriptomics Attribute Cell Network), that jointly denoises gene expression data and identifies spatial domains in SRT. Specifically, stACN first learns clean dual cell networks using a graph noise model, and then derives compatible cell features through joint tensor decomposition of the denoised networks. Experimental results demonstrate that stACN effectively enhances data quality, as measured by clustering agreement with reference annotations (Adjusted Rand Index, ARI), and facilitates spatial domain analysis in SRT datasets.

Spatially resolved transcriptomics (SRT) simultaneously captures gene expression and spatial localization within intact tissues, providing a powerful tool for studying tissue organization and disease progression in fields such as developmental biology and oncology. However, the additional experimental procedures required to retain spatial context often introduce substantial technical noise, resulting in data that are typically sparse and noisy, thereby posing significant challenges for downstream analysis. To address these issues, we propose a network-based integrative model, stACN, for denoising and identifying spatial domains in SRT data by leveraging the topological structure of cell networks. Specifically, stACN constructs spatial and expression graphs through representation learning, denoises the data via graph-based modeling, performs joint feature learning through matrix decomposition, and identifies spatial domains by exploiting the structure of the cell affinity graph. Extensive experiments across diverse SRT platforms demonstrate that stACN effectively delineates spatial domains, identifies domain-specific gene markers, and generalizes well across datasets. These results highlight the potential of stACN as a robust framework for the integrated analysis and denoising of SRT data.

## Full-text entities

- **Genes:** Tff1 (trefoil factor 1) [NCBI Gene 21784] {aka Bcei, PS2}, Myl7 (myosin, light polypeptide 7, regulatory) [NCBI Gene 17898] {aka MLC-2alpha, MLC2a, MYL2A, Mylc2a, RLC-A}, Cox6c (cytochrome c oxidase subunit 6C) [NCBI Gene 12864], Pax1 (paired box 1) [NCBI Gene 18503] {aka Pax-1, hbs, hunchback, un, undulated, wt}, KRT17 (keratin 17) [NCBI Gene 3872] {aka 39.1, CK-17, K17, PC2, PCHC1}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, Hebp1 (heme binding protein 1) [NCBI Gene 15199] {aka Hebp, p22HBP}, Nupr1 (nuclear protein transcription regulator 1) [NCBI Gene 56312] {aka 2310032H04Rik, Com1, p8}, Postn (periostin, osteoblast specific factor) [NCBI Gene 50706] {aka A630052E07Rik, OSF-2, Osf2, PLF, PN}, Meox1 (mesenchyme homeobox 1) [NCBI Gene 17285] {aka D330041M02Rik, Mox-1, Mox1, squig}, NTNG1 (netrin G1) [NCBI Gene 22854] {aka Lmnt1, NetG1, NetrinG1}, Aqp3 (aquaporin 3) [NCBI Gene 11828] {aka AQP-2}, NEFH (neurofilament heavy chain) [NCBI Gene 4744] {aka CMT2CC, NFH}, C1QL2 (complement C1q like 2) [NCBI Gene 165257] {aka C1QTNF10, CTRP10}, Ttr (transthyretin) [NCBI Gene 22139] {aka prealbumin}, Apoc1 (apolipoprotein C-I) [NCBI Gene 11812] {aka Apo-CIB, ApoC-IB, apo-CI, apoC-I}, Gstm3 (glutathione S-transferase, mu 3) [NCBI Gene 14864] {aka Fsc2, mGSTM5}, Cd24a (CD24a antigen) [NCBI Gene 12484] {aka Cd24, HSA, Ly-52, nectadrin}
- **Diseases:** Cancer (MESH:D009369), DCIS (MESH:D002285), LCIS (MESH:D000071960), ARI (MESH:D000275), IDC (MESH:D044584), metastasis (MESH:D009362), stACN (MESH:D020969), Breast cancer (MESH:D001943)
- **Chemicals:** BANKSY (-), H&amp;E (MESH:D006371)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** stACN — Muntiacus muntjak (Barking deer), Spontaneously immortalized cell line (CVCL_9126)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12799013/full.md

## References

74 references — full list in the complete paper: https://tomesphere.com/paper/PMC12799013/full.md

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Source: https://tomesphere.com/paper/PMC12799013