EPCO-27. SMINT AND SPAMTP: INTEGRATIVE SPATIAL ANALYSIS TOOLS REVEAL METABOLIC AND TRANSCRIPTIONAL DRIVERS OF INVASION IN IDH-MUTATED GLIOMA

Abstract BACKGROUND Spatial multi-omics enables deep interrogation of tumor ecosystems, yet analytical tools for integrating diverse spatial modalities remain limited. This is particularly critical in IDH-mutated gliomas, which infiltrate normal brain and evade surgical cure. To uncover spatially resolved molecular drivers of invasion, we developed two complementary tools: SMINT, a python package for spatial registration and integration of transcriptomics and metabolomics, and spaMTP, an R package for unified analysis of MALDI-imaging and transcriptomic data. METHODS We profiled five IDH-mutated lower-grade astrocytomas using spatial transcriptomics (10x Xenium), imaging mass spectrometry (MALDI-TOF), immunofluorescence, and single-cell RNA-seq across serial tissue sections. SMINT enabled multi-modal image alignment, segmentation, and integration of metabolomic and transcriptomic data. spaMTP facilitated metabolite annotation, cell-centric statistical testing, and joint visualization with transcriptomic features. Six additional lower-grade tumors were profiled with single-cell RNA-seq for validation. RESULTS We identified multinucleated OPC-like tumor cells enriched at the leading edge of gliomas, co-localizing with white matter tracts and characterized by cytoskeletal remodeling. Integrative analysis revealed spatial heterogeneity in 2-hydroxyglutarate and accumulation of glycerophosphocholine in these invasive niches. This niche was also characterized by enrichment of multi-nucleated OPC-like tumor cells and actin filaments, indicative of white matter tracts. These findings suggest invasion mediated by OPC-like cells driving enhanced membrane turnover and remodelling, facilitated by white matter tracts. CONCLUSIONS SMINT and spaMTP enable robust, scalable analysis of spatial multi-omics data and provide a novel framework to uncover mechanisms of glioma invasion. These tools offer a powerful approach to studying how tumor cells invade surrounding brain tissue and adapt to their local environment, providing new insights into the spatial biology of glioma.