CCI

CCI maps single-cell RNA sequencing (scRNA-seq) profiles from bone marrow mononuclear cells (BMMCs) onto a hematopoietic reference to identify healthy counterparts and analyze developmental trajectories in leukemogenesis.

Key Features:

• Projection of Leukemia Cells: Projects leukemia cells onto a comprehensive hematopoietic reference framework using scRNA-seq data from BMMCs, including analysis of ~200,000 single-cell transcriptomes across 23 clinical samples.
• Identification of Healthy Counterparts: Identifies distinct healthy counterparts for leukemia cell subpopulations from each patient to link malignant subpopulations to specific normal hematopoietic states.
• Trajectory Analysis: Compares developmental paths of leukemia cells with their identified healthy counterparts to reveal how developmental termination at distinct phases produces leukemia subpopulations and heterogeneity.
• Predictive Capabilities: Predicts leukemia subtypes, cellular heterogeneity, and stemness characteristics for individual patients based on mapping to the hematopoietic reference.
• Dynamic Analysis of Treatment Phases: Analyzes cell population changes across diagnosis, refractory, remission, and relapse phases, and reports that healthy counterparts of relapsed leukemia cells localize closer to the root of the hematopoietic tree.
• Unified Framework for Leukemogenesis: Integrates leukemogenesis analysis with a hematopoietic reference framework to provide a consistent comparative context for normal and malignant hematopoiesis.

Scientific Applications:

• Mapping Origins and Progression: Maps leukemia cells to normal hematopoietic states to investigate origins and developmental progression of leukemia subtypes.
• Characterizing Heterogeneity and Stemness: Assesses intra-patient cellular heterogeneity and stemness properties by comparing malignant subpopulations to healthy counterparts.
• Treatment-Phase Monitoring: Tracks shifts in cell population composition across diagnosis, refractory, remission, and relapse to study treatment-associated dynamics.
• Reference Atlas Usage: Uses a detailed hematopoietic reference built from BMMC scRNA-seq to contextualize leukemogenesis research across clinical samples.

Methodology:

Projects leukemia scRNA-seq profiles from BMMCs onto a hematopoietic reference by integrating multiple statistical methods to identify healthy counterparts, compare developmental trajectories, and predict subtypes, heterogeneity, and stemness.