“…However, for a given point pattern of multiple cell types, such spatial summary functions typically operate in a pairwise fashion, which involves all possible comparisons of one cell type to another, but not all types simultaneously. Shannon entropy (20) initially proposed in Information Theory to measure the heterogeneity in observations, has gained popularity in a wide range of applied sciences such as ecology and geography (21,22,23), evolutionary biology (24), landscapes (21,25), and recently in cancer research (26,27). For instance, Heindl et al (26) investigated the microenvironmental diversity of ovary tumors and the corresponding local metastasis sites including omentum, peritoneum, lymph node, and appendix by accounting for the collective characteristics of all cell types simultaneously via Shannon diversity index.…”