MoTRUST: adaptive semantic protection for mosaic single-cell integration and molecular recovery

Single-cell multi-omics reveals complementary aspects of cellular identity, but heterogeneous assays produce incomplete modality combinations. Integrating these mosaic measurements while preserving biological structure and recovering missing molecular information remains challenging. We present MoTRUST, combining neural representations, adaptive semantic protection, molecular prediction and conditional residual diffusion. MoTRUST ranked first in overall integration across 30 tasks spanning six scenarios and surpassed the strongest evaluated controls on six of eleven development recovery endpoints. Conditional residual diffusion reduced aggregate marginal prediction scores by 4.4-5.1% across three ATAC-to-RNA data sources while preserving point predictions. Together, these capabilities enable accurate mosaic integration and molecular recovery for multimodal characterization of cellular heterogeneity.