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We present geneSCOPE (gene Spatial Co-Occurrence of Pairwise Expression), a framework that integrates ecology-inspired spatial statistics with network analysis to explicitly capture measurement scale and spatial information. In this framework, molecules are binned on a grid with a width selected near the mode of the per-gene unit-invariant knee distribution derived from Morisita\u2019s ${I}_{\\delta }$\u2013width curves. Pairwise adjacency-weighted spatial associations are quantified using Lee\u2019s L. Then, a spatial gene network is assembled, and gene modules are identified via consensus clustering. Cell\u2013cell interactions among various cell types are identified based on high Lee\u2019s L with low cell-level co-expression (Pearson\u2019s $r$). When applied to transcriptome data derived from human colorectal cancer and lymph node Xenium tissue sections (N\u2009=\u20093 and 1, respectively), geneSCOPE recovered spatial gene modules that mapped to microanatomical compartments such as invasive margins, luminal epithelium, fibroblast-rich territories, and germinal-center subdomains. Further, it highlighted intercellular neighborhood patterns at tumor\u2013stroma interfaces characterized by the co-occurrence of leucine-rich repeat-containing G protein\u2013coupled receptor 5 (LGR5)-marked stem-like tumor programs and complement component 3 (C3)-centered fibroblast\/complement-associated niches. Using the Search Tool for the Retrieval of Interacting Genes\/Proteins (STRING) database as an external reference for benchmarking, geneSCOPE showed the highest concordance with known interacting gene pairs among the compared methods. In conclusion, geneSCOPE provides a scalable, interpretable, and cross-study comparable framework for gene-centric spatial analysis.<\/jats:p>","DOI":"10.1093\/bib\/bbag302","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T11:45:21Z","timestamp":1779277521000},"source":"Crossref","is-referenced-by-count":0,"title":["geneSCOPE: gene spatial co-occurrence of pairwise expression"],"prefix":"10.1093","volume":"27","author":[{"given":"Shicheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Graduate School of Biological Sciences, Tokyo University of Science , Yamazaki 2669, Noda City, Chiba 278-0022 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Saeki","sequence":"additional","affiliation":[{"name":"Research Institute for Biomedical Science, Tokyo University of Science , Yamazaki 2669, Noda City, Chiba 278-0022 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