Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia.
Joint profiling of DNA and proteins in single cells to dissect genotype-phenotype associations in leukemia.
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DOI：
10.1038/s41467-021-21810-3
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发表时间：
2021-03-11
影响因子：
16.6
通讯作者：
Abate AR
中科院分区：
文献类型：
--
作者：
Demaree B;Delley CL;Vasudevan HN;Peretz CAC;Ruff D;Smith CC;Abate AR
急性髓性白血病的研究依赖于DNA测序和流式细胞术的免疫表型作为疾病表征的主要工具。然而，白血病肿瘤的异质性使DNA变异和免疫表型的整合变得复杂。在这里，我们介绍了DAb-seq，一种高通量同时捕获单细胞DNA基因型和细胞表面表型的技术，可以直接分析成千上万个细胞的蛋白质基因组状态。为了证明这种方法，我们分析了三名白血病患者在多个治疗时间点和疾病复发的疾病。我们观察到复杂的基因型-表型动力学，说明了疾病过程的微妙之处，以及不同临床情况下胚细胞基因型和表型之间的不一致程度。我们的结果强调了单细胞DNA和蛋白质结合测量的重要性，以充分表征白血病的异质性。目前很难在同一细胞中绘制DNA变异和表面表型，这阻碍了表型和基因型的直接联系。在这里，作者报告了同时从单细胞高通量捕获DNA基因型和细胞表面表型的DAb-seq。
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. It is currently difficult to map DNA variants and surface phenotypes in the same cells, preventing direct linkage of phenotype and genotype. Here the authors report DAb-seq for simultaneous capture of DNA genotype and cell surface phenotype from single cells at high throughput.
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单细胞基因分型证明了急性髓系白血病复杂的克隆多样性。
影响因子：
17.1
作者：
Paguirigan AL;Smith J;Meshinchi S;Carroll M;Maley C;Radich JP
通讯作者：
Radich JP
影响因子：
20.3
作者：
Appelbaum, Frederick R.;Bernstein, Irwin D.
通讯作者：
Bernstein, Irwin D.
影响因子：
4.7
作者：
Gong, Haibiao;Holcomb, Ilona;Ramakrishnan, Ramesh
通讯作者：
Ramakrishnan, Ramesh
DOI：
10.1056/nejmoa1701719
发表时间：
2017-07-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Jaiswal S;Natarajan P;Silver AJ;Gibson CJ;Bick AG;Shvartz E;McConkey M;Gupta N;Gabriel S;Ardissino D;Baber U;Mehran R;Fuster V;Danesh J;Frossard P;Saleheen D;Melander O;Sukhova GK;Neuberg D;Libby P;Kathiresan S;Ebert BL
通讯作者：
Ebert BL
DOI：
10.1088/1742-5468/2008/10/p10008
发表时间：
2008-10-01
影响因子：
2.4
作者：
Blondel, Vincent D.;Guillaume, Jean-Loup;Lefebvre, Etienne
通讯作者：
Lefebvre, Etienne