Unlocking cross-modal interplay of single-cell joint profiling with CellMATE.

A key advantage of single-cell multimodal joint profiling is the modality interplay, which is essential for deciphering the cell fate. However, while current analytical methods can leverage the additive benefits, they fall short to explore the synergistic insights of joint profiling, thereby diminishing the advantage of joint profiling. Here, we introduce CellMATE, a Multi-head Adversarial Training-based Early-integration approach specifically developed for multimodal joint profiling. CellMATE can capture both additive and synergistic benefits inherent in joint profiling through auto-learning of multimodal distributions and simultaneously represents all features into a unified latent space. Through extensive evaluation across diverse joint profiling scenarios, CellMATE demonstrated its superiority in ensuring utility of cross-modal properties, uncovering cellular heterogeneity and plasticity, and delineating differentiation trajectories. CellMATE uniquely unlocks the full potential of joint profiling to elucidate the dynamic nature of cells during critical processes as differentiation, development, and diseases.