Engineering Spatial and Molecular Features from Cellular Niches to Inform Predictions of Inflammatory Bowel Disease
This work addresses a persistent clinical problem in gastroenterology by providing a potential new diagnostic tool with explainable insights into disease mechanisms.
The study tackled the challenge of differentiating between Crohn's disease and ulcerative colitis in inflammatory bowel disease by developing a computational framework using spatial transcriptomics, achieving accuracies of 0.774 for three-class classification and 0.916 for distinguishing IBD from healthy tissue.
Differentiating between the two main subtypes of Inflammatory Bowel Disease (IBD): Crohns disease (CD) and ulcerative colitis (UC) is a persistent clinical challenge due to overlapping presentations. This study introduces a novel computational framework that employs spatial transcriptomics (ST) to create an explainable machine learning model for IBD classification. We analyzed ST data from the colonic mucosa of healthy controls (HC), UC, and CD patients. Using Non-negative Matrix Factorization (NMF), we first identified four recurring cellular niches, representing distinct functional microenvironments within the tissue. From these niches, we systematically engineered 44 features capturing three key aspects of tissue pathology: niche composition, neighborhood enrichment, and niche-gene signals. A multilayer perceptron (MLP) classifier trained on these features achieved an accuracy of 0.774 +/- 0.161 for the more challenging three-class problem (HC, UC, and CD) and 0.916 +/- 0.118 in the two-class problem of distinguishing IBD from healthy tissue. Crucially, model explainability analysis revealed that disruptions in the spatial organization of niches were the strongest predictors of general inflammation, while the classification between UC and CD relied on specific niche-gene expression signatures. This work provides a robust, proof-of-concept pipeline that transforms descriptive spatial data into an accurate and explainable predictive tool, offering not only a potential new diagnostic paradigm but also deeper insights into the distinct biological mechanisms that drive IBD subtypes.