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Targeted single-cell mRNA-sequencing reduces sequencing costs by profiling reduced gene sets that capture biological information with a minimal number of genes. Here we introduce an active learning method that identifies minimal but highly informative gene sets that enable the identification of cell types, physiological states and genetic perturbations in single-cell data using a small number of genes. Our active feature selection procedure generates minimal gene sets from single-cell data by employing an active support vector machine (ActiveSVM) classifier. We demonstrate that ActiveSVM feature selection identifies gene sets that enable ~90% cell-type classification accuracy across, for example, cell atlas and disease-characterization datasets. 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