CellMemory: Hierarchical Interpretation of Out-of-Distribution Cells Using Bottlenecked Transformer

Qifei Wang

Track: Main track (up to 8 pages)

Abstract: Applying machine learning to cellular data presents several challenges. One such challenge is making the methods interpretable concerning both the cellular information and its context. Another less-explored challenge is the accurate representation of cells outside existing references, referred to as out-of-distribution (OOD) cells. OOD cells arise from physiological conditions (e.g., diseased vs. healthy) or technical variations (e.g., single-cell references vs. spatial queries). Inspired by the Global Workspace Theory in cognitive neuroscience, we introduce CellMemory, a bottlenecked Transformer with improved generalization designed for the hierarchical interpretation of OOD cells. CellMemory outperforms large-scale foundation models pre-trained on tens of millions of cells, even without pre-training. Moreover, it robustly characterizes malignant cells and their founder cells across different patients, revealing cellular changes caused by the diseases. We further propose leveraging CellMemory’s capacity to integrate multi-modalities and phenotypic information, advancing toward the construction of VIRTUAL ORGAN.

Submission Number: 49