TY - JOUR A1 - Song, Xiaoyu A1 - Shang, Yuqing A1 - Ehrlich, Michelle E. A1 - Roussos, Panos A1 - Yuan, Guo-Cheng A1 - Wang, Pei T1 - QuadST identifies cell–cell interaction–changed genes in spatially resolved transcriptomics data Y1 - 2025/08/01 JF - Genome Research JO - Genome Research SP - 1821 EP - 1831 DO - 10.1101/gr.279859.124 VL - 35 IS - 8 UR - http://genome.cshlp.org/content/35/8/1821.abstract N2 - 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. ER -