Niche Trajectory Analysis of Spatial Omics Data

About This Grant

PROJECT SUMMARY The maintenance and function of a tissue/organ depends on cell-cell interactions among different cell types. The cell-cell interactome responds and regulates the tissue microenvironment (ME) which is altered in physiological processes such as development and aging, or during the onset and progression of various human diseases. Spatial transcriptomics offers an opportunity to systematically characterize the structural organization of the ME and its changes in various diseases. On the other hand, it requires the development of sophisticated computational methods to achieve these goals. In this project, we will develop a unifying modeling framework, called, ONTraC, and apply it to systematically characterize ME organization in multiple mammalian tissues. A unique feature of the ONTraC framework is that it uses the niche as the basic structural component instead of a cell, as commonly done. The specific aims are: 1. To develop a new framework for constructing niche trajectories from spatial transcriptomic and epigenomic data; 2. To extend the ONTraC framework for analyzing subcellular RNA localization patterns; and 3. To comprehensively characterize the ME organization in acute kidney injury mice through a systems biology approach. Taken together, our proposed research will generate powerful computational tools that will enable biologists and clinicians to investigate the structure and function of ME organization in health and diseases.