dioscRi enables transferable prediction of clinical outcomes in multi-parameter cytometry data

Abstract Multi-parameter cytometry technologies enable high-dimensional analysis of immune cell populations at single-cell resolution. Deep learning has emerged as a transformative tool for analyzing these datasets, but existing methods often struggle with transferability across datasets due to technical variability, batch effects and identification of biologically relevant cell populations, limiting their utility in clinical research. We present dioscRi, a transferable deep learning framework that integrates a maximum mean discrepancy variational autoencoder for normalization and de-noising, enhancing cross-dataset compatibility. Changes in cell type proportions and marker expression are identified by structuring these features within biologically or empirically derived cell type hierarchies. These hierarchies are incorporated directly into an overlapping group LASSO model, improving the prediction of clinical outcomes. When applied to a coronary artery disease study, dioscRi recapitulated several known immune associations. Benchmarking across multiple datasets demonstrated dioscRi’s ability to generalize and outperform existing methods, establishing it as a versatile and interpretable tool for cytometry data analysis.