scCADE: A Superior Tool for Predicting Perturbation Responses in Single-Cell Gene Expression Using Contrastive Learning and Attention Mechanisms

The advent of single-cell transcriptomics has revolutionized our ability to analyze cellular heterogeneity and dynamics at a fine resolution, yet covering the vast array of potential perturbations remains challenging due to biological variability. To address this, we propose scCADE, a novel computational approach utilizing contrastive learning and an attention mechanism to decouple gene expression signatures and predict cellular responses to perturbations. scCADE excels in predicting responses in cells to perturbations observed in other cells but not yet seen in the target cells. Through rigorous ablation studies and validation across three datasets involving drug and gene editing perturbations, scCADE consistently outperformed existing methods, underscoring its efficacy and potential to advance genomics and personalized medicine by accurately forecasting responses to novel perturbations.