ALPINE can accurately extract condition-associated genes. (A) Box plot of the AUPRC of ALPINE, scDisInfact, and scParser on condition-associated gene detection in four scenarios. (B) Algorithm run time (execution) for ALPINE, scParser, and scDisInfact, and hyperparameter searching (optimization) for ALPINE (which tests 100 hyperparameter sets) and scParser (which tests five hyperparameter sets). scDisInfact does not provide an optimization function. (C) UMAP plot of cell embeddings with batch and condition effects removed, colored by cell type. Highlighted are cells under two conditions with distinct gene perturbations. ALPINE's condition embeddings capture condition-associated signatures, accurately identifying stimulation-associated (types 4–9) and severity-associated cell types (types 10–15).