Comprehensive multi-omics single-cell data integration reveals greater heterogeneity in the human immune system

Single-cell transcriptomics enables the definition of diverse human immune cell types acrossmultiple tissues and disease contexts. Further deeper biological understanding requires comprehensive integration of multiple single-cell omics (transcriptomic, proteomic, and cell-receptor repertoire). To improve the identification of diverse cell types and the accuracy of cell-type classification in multi-omics single-cell datasets, we developed SuPERR, a novel analysis workflow to increase the resolution and accuracy of clustering and allow for the discovery of previously hidden cell subsets. In addition, SuPERR accurately removes cell doublets and preventswidespread cell-type misclassification by incorporating information from cell-surface proteins and immunoglobulin transcript counts. This approach uniquely improves the identification of heterogeneous cell types and states in the human immune system, including rare subsets of antibody-secreting cells in the bonemarrow.