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This study introduces a multimodal framework that learns subcellularly resolved cell embeddings by integrating RNA expression profiles, protein sequence representations, and protein structural information using a cross-attention architecture. By focusing on the subcellular localization of molecules, the approach captures the intricate interactions and functional properties of proteins within distinct cellular compartments. The resulting embeddings provide a fine-grained representation of cells, preserving spatially organized biological information and offering a novel perspective on molecular interactions and functions at the subcellular level.
By integrating transcriptomic, sequence, and structural data, this framework reveals a new dimension of cellular organization that traditional methods overlook.
Existing cell embedding methods predominantly rely on transcriptomic or proteomic measurements and represent each cell as a holistic entity, thereby overlooking the subcellular localization of individual molecules. Moreover, they rarely incorporate protein structural information, despite its fundamental role in determining molecular interactions and functions. In this work, we propose a multimodal framework for learning subcellularly resolved cell embeddings by jointly leveraging RNA expression profiles, protein sequence representations, and protein structural information. Specifically, we employ a cross-attention architecture to integrate transcriptomic, sequence, and structural modalities and model their interactions within distinct subcellular compartments. The resulting embeddings represent each cell through its fine-grained subcellular organization, capturing both molecular expression patterns and the functional properties of the associated proteins. By learning cell representations at subcellular resolution, our framework preserves spatially organized biological information while integrating complementary signals across multiple molecular levels. To the best of our knowledge, this is the first framework that produces subcellularly resolved cell embeddings by jointly incorporating transcriptomic information, protein sequence representations, and protein structural knowledge within a unified cross-modal learning paradigm.
