Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia

Abstract Studies of acute myeloid leukemia rely on DNA sequencing and immunophenotyping by flow cytometry as primary tools for disease characterization. However, tumor heterogeneity complicates integration variants immunophenotypes from separate measurements. Here we introduce DAb-seq, a technology simultaneous capture genotype cell surface phenotype single cells at high throughput, enabling direct profiling proteogenomic states in tens thousands cells. To demonstrate the approach, analyze three patients with over multiple treatment timepoints recurrences. We observe complex genotype-phenotype dynamics that illustrate subtlety process degree incongruity between blast different clinical scenarios. Our results highlight importance combined single-cell protein measurements to fully characterize leukemia.