Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia
Year: 2021
Type: article
Abstract: Studies of acute myeloid leukemia rely on DNA sequencing and immunophenotyping by flow cytometry as primary tools for disease characterization. However, leukemia tumor heterogeneity complicates integration of DNA variants and immunophenotypes from separate measurements. Here we introduce DAb-seq, a technology for simultaneous capture of DNA genotype and cell surface phenotype from single cells at high throughput, enabling direct profiling of proteogenomic states in tens of thousands of cells. To demonstrate the approach, we analyze the disease of three patients with leukemia over multiple treatment timepoints and disease recurrences. We observe complex genotype-phenotype dynamics that illustrate the subtlety of the disease process and the degree of incongruity between blast cell genotype and phenotype in different clinical scenarios. Our results highlight the importance of combined single-cell DNA and protein measurements to fully characterize the heterogeneity of leukemia.
Source: Nature Communications
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: National Science Foundation, U.S. Department of Health and Human Services, American Cancer Society, Conquer Cancer Foundation, Damon Runyon Cancer Research Foundation, Alex's Lemonade Stand Foundation for Childhood Cancer, American Society of Clinical Oncology, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences
Awards: Gigapixel digital PCR in Giant Unilamellar Vesicles, G3388539116, G4595722220, Detecting cell surface fingerprints of cancer initiating cells in acute myeloid leukemia to flag them for destruction, G5279806633, CAREER: Massively-parallel single-cell genomics and transcriptomics with droplet microfluidics, G549111027, Microfluidic immunoprofiling for biomarker discovery in rheumatoid arthritis, G6671297155
OpenAlex ID: W3134217762