CALM: Interpretable Cross-Modal Alignment for Biomarker Discovery from Unpaired Data

Jueqi Wang, Zachary Jacokes, John Darrell Van Horn, Kevin A. Pelphrey, Michael C. Schatz, Archana Venkataraman

The interaction between brain structure and genetic influences is key to understanding neuropsychiatric disorders. However, most large-scale datasets are unimodal, providing either neuroimaging or genetics data. We propose CALM, a framework that learns interpretable associations between brain ROIs and genetic pathways from completely disjoint populations. CALM aligns the two modalities in a shared latent space via linear projections that simultaneously match the class-conditional latent distributions and ensure group separability. These projections provide interpretable pathway--ROI associations. When trained on unimodal imaging and genetics datasets, CALM generalizes to an unseen paired dataset, outperforming several state-of-the-art methods and ablation baselines. We also demonstrate stability of the learned associations against a paired baseline. Our experiments on autism spectrum disorder reveal immune and metabolic pathways linked to specific cortical regions and are consistent with established literature. Thus, CALM opens the door to leveraging large unimodal repositories for studying cross-modal interactions in brain disorders across disparate datasets.