STORM: spatial transcriptomics optimization by resolution via matrix factorization.

Classic RNA sequencing dissociates cells from their native tissue architecture, discarding spatial information that critically shapes transcriptional programs in development, homeostasis, and cancer. However, current ST platforms often produce incomplete and noisy profiles due to technical limitations and tissue variability. These limitations obscure biologically meaningful spatial patterns and hinder downstream interpretation. Here, we introduce STORM (spatial transcriptomics optimization by resolution via matrix factorization), a machine learning framework that improves the fidelity of spatial transcriptomics data under severe sparsity. STORM formulates spatial transcriptomics recovery as a low-rank tensor decomposition problem and integrates multimodal biological priors through a principled regularization strategy. Specifically, the model jointly captures spatial continuity, tissue morphology derived from whole-slide histology images, and gene-gene interaction structure informed by protein-protein interaction networks. This method enables accurate reconstruction at unobserved locations while preserving biologically meaningful spatial structure. Across diverse lung tissue profiles, including both healthy and malignant samples, STORM consistently outperforms existing state-of-the-art methods in recovering spatial gene-expression patterns and remains robust even when a majority of spatial measurements are missing. By explicitly embedding biological structure into the reconstruction process, STORM provides a reliable foundation for high-resolution spatial transcriptomic analysis in settings where experimental data are sparse or incomplete. Availability: The source code developed in this study is publicly available at https://github.com/denizgurarslan/STORM.