Abstract: Segmentation or other classification of digital pathology images with a deep learning model allows for sophisticated spatial features for cancer diagnosis to be extracted in an automated, fast, and accurate manner. A tiered analysis of tissue structure based in part on deep learning methods is provided. First, tissues depicted in a digital pathology image are segmented into cellular compartments (e.g., epithelial and stromal compartments). Second, the heterogeneity in the different cellular compartments are examined based on a clustering algorithm. Tissue can then be characterized in terms of inertia (or other spatial measures or features), which can be used to recognize disease. In some instances, multidimensional inertia (i.e., inertia computed in different cellular compartments or clustered components) can be used as an indicator of disease and its outcome.