Identification of cell types carrying CH mutations by combined single-cell surface protein and genotype analysis. (A) Overview of COVID-19 cohorts with TET2mt CH, DNMT3Amt CH, TET2mt DNMT3Amt (comutant) CH, and without CH (CH⁻), analyzed using single-cell proteogenomics (Tapestri assay). Mutations and VAFs are shown above, and patient ages are shown below, the figurines. Sample identifier is shown inside the figurines. (B) Uniform manifold approximation and projection (UMAP) projections showing the distribution of 28 941 cells from single-cell proteogenomics analysis from 13 patient samples, colored by cell types. The bar below shows the proportion of cells in each cell type. (C) UMAP projections of the single-cell proteogenomics data showing only mutated cells, which are then stratified by TET2 and DNMT3A mutated cells, demonstrating the myeloid and lymphoid lineage restriction in TET2mt and DNMT3Amt cells, respectively. The bars below show the proportion of cells in each cell type. (D-E) Bar plots showing the proportion of cells in each cell type stratifying cells by sample/patient genotype (D) and by cell genotype (E). Although TET2 mutations had a clear myeloid lineage restriction bias, DNMT3A mutations were seen in myeloid and lymphoid lineages, respectively. cDC, classical dendritic cells; gdT, γδ T cells; Int, intermediate; MAIT, mucosal-associated invariant T cells; mono, monocytes; pDC, plasmacytoid dendritic cells; Treg, regulatory T cells; WT, wild type.