Multiscale Microenvironment Vector Space Projection for Uncovering Diverse Pathological Biomarker

Due to the challenge of uncovering biologically meaningful spatial tissue patterns from standard H&E-stained whole-slide images (WSIs) without relying on multiplexed staining or fixed-scale modeling, a unified framework is proposed for spatial biomarker discovery that integrates cell classification, adaptive multi-scale microenvironment construction, and colocalization pattern analysis. Cell-level predictions assign discrete, semantically meaningful types that serve as the basis for microenvironment modeling, where physical adjacency initializes local ecological features and a combination of spatial competition-based seed selection with homogeneity-constrained recursive region growing allows microenvironments to expand from locally pure regions in a data-driven manner, capturing heterogeneity across scales without predefined spatial ranges. Microenvironment-level cell composition features are then used to construct a colocalization feature space, explicitly modeling spatial relationships among cell types, and differential biomarkers are identified via a distributional comparison framework that systematically detects group-specific colocalization patterns. Experiments demonstrate that this framework reliably discovers discriminative and biologically interpretable spatial biomarkers from H&E images alone, exhibiting robustness in tissues with complex structures and heterogeneous scales, and offering a flexible, extensible paradigm for spatial phenotypic biomarker discovery in standard histopathology.