Integration of single-cell and spatial transcriptomes represents a fundamental strategy to enhance spatial data quality. However, existing methods for mapping single-cell data to spatial coordinates struggle with large-scale data sets comprising millions of cells. Here, we introduce Polyomino, an intelligent region-allocation method inspired by the region-of-interest (ROI) concept from image processing. By using gradient descent, Polyomino allocates cells to structured spatial regions that match the most significa…