An Information Geometry approach to model topological trajectories and Gene Expression Radius from UMAP geometry

Understanding the relationship between gene expression dynamics and cellular identity remains a central challenge in single-cell biology. Here, we introduce a novel computational and mathematical framework that integrates information geometry, fuzzy topology, and UMAP analysis to model gene expression landscapes derived from single-cell RNA sequencing data.

We formalize gene expression data as a fuzzy topological space, where interactions between expression points are governed by probabilistic distributions inspired by manifold learning approaches such as UMAP. Within this framework, we define an information geometric structure through a Fisher metric induced by these distributions, enabling the computation of geodesic trajectories that capture cellular differentiation processes.

A key contribution of this work is the derivation of analytical conditions, expressed as expression radius formulas, that characterize local neighborhoods in gene expression space. These conditions allow for the identification of genes associated with stem cell states and predictions in transitional cell types in future work.

Application of the proposed framework to single-cell datasets reveals biologically meaningful gene sets enriched in key regulatory pathways and transcription factors, demonstrating the capacity of our approach to uncover latent structure in complex gene expression data.

Our results suggest that integrating differential geometry with statistical learning theory offers a powerful paradigm for modeling genotype–phenotype relationships and cellular state transitions, with potential implications for precision medicine and systems biology.