Details

Autor(en) / Beteiligte

• Granja, Jeffrey M
• Klemm, Sandy
• McGinnis, Lisa M
• Kathiria, Arwa S
• Mezger, Anja
• Corces, M Ryan
• Parks, Benjamin
• Gars, Eric
• Liedtke, Michaela
• Zheng, Grace X Y
• Chang, Howard Y
• Majeti, Ravindra
• Greenleaf, William J

Titel

Single-cell multiomic analysis identifies regulatory programs in mixed-phenotype acute leukemia

Ist Teil von

• Nature biotechnology, 2019-12, Vol.37 (12), p.1458-1465

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Identifying the causes of human diseases requires deconvolution of abnormal molecular phenotypes spanning DNA accessibility, gene expression and protein abundance . We present a single-cell framework that integrates highly multiplexed protein quantification, transcriptome profiling and analysis of chromatin accessibility. Using this approach, we establish a normal epigenetic baseline for healthy blood development, which we then use to deconvolve aberrant molecular features within blood from patients with mixed-phenotype acute leukemia . Despite widespread epigenetic heterogeneity within the patient cohort, we observe common malignant signatures across patients as well as patient-specific regulatory features that are shared across phenotypic compartments of individual patients. Integrative analysis of transcriptomic and chromatin-accessibility maps identified 91,601 putative peak-to-gene linkages and transcription factors that regulate leukemia-specific genes, such as RUNX1-linked regulatory elements proximal to the marker gene CD69. These results demonstrate how integrative, multiomic analysis of single cells within the framework of normal development can reveal both distinct and shared molecular mechanisms of disease from patient samples.