Spatial integration of multi-omics data from serial sections using the novel Multi-Omics Imaging Integration Toolset.

BACKGROUND: Truly understanding the cancer biology of heterogeneous tumors in precision medicine requires capturing the complexities of multiple omics levels and the spatial heterogeneity of cancer tissue. Techniques like mass spectrometry imaging (MSI) and spatial transcriptomics (ST) achieve this by spatially detecting metabolites and RNA but are often applied to serial sections. To fully leverage the advantage of such multi-omics data, the individual measurements need to be integrated into 1 dataset. RESULTS: We present the Multi-Omics Imaging Integration Toolset (MIIT), a Python framework for integrating spatially resolved multi-omics data. A key component of MIIT's integration is the registration of serial sections for which we developed a nonrigid registration algorithm, GreedyFHist. We validated GreedyFHist on 244 images from fresh-frozen serial sections, achieving state-of-the-art performance. As a proof of concept, we used MIIT to integrate ST and MSI data from prostate tissue samples and assessed the correlation of a gene signature for citrate-spermine secretion derived from ST with metabolic measurements from MSI. CONCLUSION: MIIT is a highly accurate, customizable, open-source framework for integrating spatial omics technologies performed on different serial sections.