Scalable Mapping of Tumor Microenvironment Inspired by Geographic Information System

Nonmutational epigenetic reprogramming and genome instability are hallmarks of cancer, intricately tied to the tumor microenvironment. Understanding these processes requires scalable, spatially resolved tools at the molecular, cellular, and histological levels. The purpose of spatial omics, similar to geographic information systems (GIS), is to enable the analysis of spatial relationships across complex biological features. In GIS, geospatial indexing allows us to effortlessly search for patterns and events—such as Dating Apps, Chat Apps or Proximity searches (Uber, Lyft, Yelp, Google)—using real-time updates and interactive maps. In contrast, current spatial omics technologies lack scalability, real-time integration, and interactive visualization. Scalable mapping of the tumor microenvironment at multiple levels is essential to decipher tumor progression and identify new therapeutic targets. Inspired by geospatial indexing, I will develop an interdisciplinary toolbox, ScaleMAP, for mapping single-cell spatial epigenetics and genomics within the tumor microenvironment. ScaleMAP offers high-throughput, high-resolution, scalable, and interactive mapping across large tissue sections. 3D reconstruction of ScaleMAP will enable the investigation of cancer evolution in three dimensions. Like Google Maps, ScaleMAP treats tissues as ""biological terrains,"" allowing researchers to interactively zoom into specific areas of interest across molecular, cellular, and histological levels to extract valuable insights. We will also develop GIS-inspired analytical packages for ScaleMAP data. Furthermore, we will adapt ScaleMAP for formalin-fixed paraffin-embedded samples and apply it to clinically archived paired primary and metastatic colorectal cancer samples to dissect metastasis. Beyond cancer, ScaleMAP has broad applications in biological research and digital pathology, offering powerful tools for exploration, diagnosis, and therapeutic discovery.""