Integration of Multiple Spatial Omics Modalities Reveals Unique Insights into Molecular Heterogeneity of Prostate Cancer

This project introduces a spatial multi-omics (SMOx) pipeline integrating MALDI-2 mass spectrometry imaging (MSI) with Visium spatial transcriptomics (ST) and single-nucleus RNA sequencing (snRNA-seq) to investigate molecular heterogeneity in human prostate cancer (PCa). MALDI-2 MSI was used to map lipid distributions with enhanced sensitivity compared to conventional MALDI, enabling detailed visualization of metabolic alterations across tissue regions. Through non-rigid co-registration via H&E images and Gaussian-weighted granularity matching, MSI data were spatially aligned with transcriptomic and histological layers. This integration revealed lipidgene expression relationships associated with distinct cell populations and pathological states within heterogeneous prostate tissues. The resulting dataset provides a high-resolution molecular atlas of PCa, demonstrating the power of MSI-driven spatial multi-omics to uncover lipid-based signatures that refine tissue annotation and support molecular pathology studies.