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

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.