# QuadST identifies cell–cell interaction–changed genes in spatially resolved transcriptomics data

**Authors:** Xiaoyu Song, Yuqing Shang, Michelle E. Ehrlich, Panos Roussos, Guo-Cheng Yuan, Pei Wang

PMC · DOI: 10.1101/gr.279859.124 · Genome Research · 2025-08-01

## TL;DR

QuadST is a new method that identifies genes affected by cell-cell interactions in spatial transcriptomics data without needing to specify cell pairs.

## Contribution

QuadST introduces a novel statistical approach to identify interaction-changed genes without requiring predefined cell pairs.

## Key findings

- QuadST effectively controls type I error and improves power over existing methods in simulations.
- Real data applications reveal biologically significant interaction-changed genes across various cell types.

## Abstract

Recent advances in spatially resolved transcriptomics (SRT) have provided valuable avenues for identifying cell–cell interactions and their critical roles in diseases. Here, we introduce QuadST, a novel statistical method for the robust and powerful identification of cell–cell interactions and their impacted genes in single-cell SRT. QuadST models interactions at different cell–cell distance quantile levels and innovatively contrasts signals to identify interaction-changed genes, which exhibit stronger signals at shorter distances. Unlike other methods, QuadST does not require the specification of interacting cell pairs. It is also robust against unmeasured confounding factors and measurement errors of the data. Simulation studies demonstrate that QuadST effectively controls the type I error, even in misspecified settings, and significantly improves power over existing methods. Applications of QuadST to real data sets reveal biologically significant interaction-changed genes across various cell types.

## Full-text entities

- **Genes:** Cplx1 (complexin 1) [NCBI Gene 12889] {aka 921-S}, Nsmf (NMDA receptor synaptonuclear signaling and neuronal migration factor) [NCBI Gene 56876] {aka Jacob, Nelf}
- **Diseases:** UMAP (MESH:C567162), cancer (MESH:D009369), neurodegenerative diseases (MESH:D019636)
- **Chemicals:** ICG (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797)

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## Figures

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## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12315707/full.md

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Source: https://tomesphere.com/paper/PMC12315707