S3-CIMA: Supervised spatial single-cell image analysis for the identification of disease-associated cell type compositions in tissue

The spatial organization of various cell types within the tissue microenvironment is a key element for the formation of physiological and pathological processes, including cancer and autoimmune diseases. Here, we present S3-CIMA, a weakly supervised convolutional neural network model that enables the detection of disease-specific microenvironment compositions from high-dimensional proteomic imaging data. We demonstrate the utility of this approach by determining cancer outcome- and cellular signaling-specific spatial cell state compositions in highly multiplexed fluorescence microscopy data of the tumor microenvironment in colorectal cancer. Moreover, we use S3-CIMA to identify disease onset-specific changes of the pancreatic tissue microenvironment in type 1 diabetes using imaging mass cytometry data. We evaluated S3-CIMA as a powerful tool to discover novel disease-associated spatial cellular interactions from currently available and future spatial biology datasets. ### Competing Interest Statement MC is a co-founder and holds stock of Scailyte AG. This work is independent of this status. CMS. is a scientific advisor to, has stock options in, and has received research funding from Enable Medicine, Inc., all outside of this work. The other authors declare no conflicts of interest.