Tissue schematics map the specialization of immune tissue motifs and their appropriation by tumors

A schematic of a biological system, i.e., a representation of its pieces, how they are combined, and what they do, would facilitate understanding its essential organization and alteration in pathogenesis or evolution. We present a computational approach for constructing tissue schematics (TSs) from high-parameter imaging data and a biological model for interpreting them. TSs map the spatial assembly of cellular neighborhoods into tissue motifs, whose modular composition, we propose, enables the generation of complex outputs. We developed our approach in human lymphoid tissue (HLT), identifying the follicular outer zone as a potential relay between neighboring zones and a core lymphoid assembly with modifications characteristic of each HLT type. Applying the TS approach to the tumor microenvironment in human colorectal cancer identified a higher-order motif, whose mutated assembly was negatively associated with patient survival. TSs may therefore elucidate how immune architectures can be specialized and become vulnerable to reprogramming by tumors.

Automated summary

A schematic of a biological system can help understand its organization and changes in pathology or evolution. Researchers have developed a computational approach to construct tissue schematics and interpret them using high-parameter imaging data and a biological model. Applying this approach to human lymphoid tissue and the tumor microenvironment in colorectal cancer revealed potential relay zones and mutations associated with patient survival.