scCobra: Contrastive cell embedding learning with domain-adaptation for single-cell data integration and harmonization

Abstract The rapid development of single-cell technologies has underscored the need for more effective methods in the integration and harmonization of single-cell sequencing data. The prevalent challenge of batch effects, resulting from technical and biological variations across studies, demands accurate and reliable solutions for data integration. Traditional tools often have limitations, both due to reliance on gene expression distribution assumptions and the common issue of over-correction, particularly in methods based on anchor alignments. Here we introduce scCobra, a deep neural network tool designed specifically to address these challenges. By leveraging a deep generative model that combines a contrastive neural network with domain adaptation, scCobra effectively mitigates batch effects and minimizes over-correction without depending on gene expression distribution assumptions. Additionally, scCobra enables online label transfer across datasets with batch effects, facilitating the continuous integration of new data without retraining, and offers features for batch effect simulation and advanced multi-omic batch integration. These capabilities make scCobra a versatile data integration and harmonization tool for achieving accurate and insightful biological interpretations from complex datasets.