Juan Xie ¹ Kyeong Joo Jung ¹ Carter Allen ² Yuzhou Chang ¹ Subhadeep Paul ¹ Zihai Li ¹ Qin Ma ¹ Dongjun Chung ^1*

• ¹ The Ohio State University, Columbus, Ohio, United States
• ² Lilly Research Laboratories, Eli Lilly (United States), Indianapolis, Indiana, United States

The advent of high throughput spatial transcriptomics (HST) has allowed for unprecedented characterization of spatially distinct cell communities within a tissue sample. While a wide range of computational tools exist for detecting cell communities in HST data, none allow for the characterization of community connectivity, i.e., the relative similarity of cells within and between found communities -an analysis task that can elucidate cellular dynamics in important settings such as the tumor microenvironment. To address this gap, we introduce the analysis of community connectivity (ACC), which facilitates understanding of the relative similarity of cells within and between communities. We develop a Bayesian multi-layer network model called BANYAN for the integration of spatial and gene expression information to achieve ACC. We demonstrate BANYAN's ability to recover community connectivity structure via a simulation study based on real sagittal mouse brain HST data. Next, we use BANYAN to implement ACC across a wide range of real data scenarios, including 10X Visium data of melanoma brain metastases and invasive ductal carcinoma, and NanoString CosMx data of human-small-cell lung cancer, each of which reveals distinct cliques of interacting cell sub-populations. An R package banyan is available at https://github.com/dongjunchung/banyan.