SIMO – Single Section Integrative Multi-Omics – spatial mapping of metabolites and lipids combined with region-specific proteomics in a single tissue slice

Technological advances in biomedical sciences have accelerated multi-omics research, enabling high-resolution spatial mapping of diverse molecular compound classes. However, integrating spatial omics often requires serial tissue sections, limiting the alignment correlation across modalities. We present a single-section integrative multi-omics (SIMO) workflow that combines metabolite and lipid imaging with histopathology and region-specific proteomics. Using MALDI-MSI, tissue staining, and laser microdissection (LMD), SIMO delivers comprehensive metabolic, lipidomic, and proteomic insight from the same sample. Using mouse cardiac tissue we develop, control, and validate the methodology resulting in ∼60 imaged lipids and ∼60 imaged metabolites at 20 µm pixel size and subsequently spatial proteomics by LMD, detecting over 5,000 proteins from the same tissue. To demonstrate the capabilities of the workflow in preclinical context, we apply SIMO to a metastasizing melanoma PDX model, identifying over 100 spatially localized lipids and metabolites, and over 5,000 proteins across metastases and non-tumor tissues in liver. SIMO enables precise ROI selection, statistical comparison of protein regulation, and alignment of metabolic and lipidomics pathways across spatial omics and region-specific proteomics, demonstrating its value as a spatial multi-omics platform.