SOmicsFusion: Multimodal Coregistration and Fusion between Spatial Metabolomics and Biomedical Imaging.

We present SOmicsFusion, a software toolbox for ’fusing’ spatial omics with classical biomedical imaging modalities, capitalizing on their inherent correspondences and complementarity when characterizing the same subject. By augmenting radiological and histological images with spatially resolved molecular profiling, this fusion offers a panoramic characterization of the biochemical perturbations underlying pathological conditions, thereby advancing our understanding of diseases like brain disorders and cancers. The cornerstone of SOmicsFusion is a coregistration tool that leverages an innovative two-stage machine learning pipeline to tackle the longstanding challenge of spatially aligning data from fundamentally different modalities, priming them for subsequent fusion analysis that often requires precise pixel-wise correspondence between the datasets. Specifically, the pipeline utilizes an original dimension reduction algorithm for representational domain alignment, followed by a Deep Learning-based method for spatial domain alignment. SOmicsFusion is demonstrated using mass spectrometry imaging (MSI)-mediated spatial metabolomics and four other modalities: magnetic resonance imaging (MRI), microscopy, brain atlas, and spatial transcriptomics. By reducing coregistration errors by 38% to 69% compared to existing pipelines, SOmicsFusion enhances the precision of associating molecule distribution with anatomy and pathology features, ultimately leading to more statistically robust findings. Furthermore, SOmicsFusion incorporates various downstream analysis tools, including overlay visualization, spatial correlation/co-expression analysis, pansharpening, and automated anatomy annotation. These tools facilitate the extraction of biological insights that would be unattainable through individual modalities alone. For instance, the coregistration and correlation between MSI and in vivo MRI datasets unveil that the spatial heterogeneity in metabolites stems from the temporal heterogeneity in the development of cerebral ischemia-reperfusion injury.