Smart spatial omics (S2-omics) optimizes region-of-interest selection to capture molecular heterogeneity in diverse tissues v2

A protocol describing the application of S2-omics on a colorectal cancer tissue section, designing 10x VisiumHD experiment. S2-omics is an end-to-end workflow that automatically selects regions of interest for spatial omics experiments using histology images. Additionally, S2-omics utilizes the resulting spatial omics data to virtually reconstruct spatial molecular profiles across entire tissue sections, providing valuable insights to guide subsequent experimental steps. Our histology image-guided design significantly reduces experimental costs while preserving critical spatial molecular variations, thereby making spatial omics studies more accessible and cost-effective. We demonstrate S2-omics’s utility in selecting a 6.5mm × 6.5mm ROI and predicting the cell-type labels for the whole slide image after conducting VisiumHD experiment on the selected ROI.