Bioinformatics Seminar
Time: 11AM
Venue: Davis Auditorium and Online
26 August 2025
Illuminating Leukemia Heterogeneity: Bimodal Single-cell Insights
Reza GhamsariWEHI Bioinformatics/Genetics and Gene Regulations
Advances in genomics have refined the characterization of acute myeloid leukemia (AML) and driven the development of novel therapies and treatment strategies. Despite this progress, AML remains a highly lethal malignancy due to its extraordinary complexity and heterogeneity, which continue to hinder efforts to fully understand the disease and its effects. In this study, we leverage paired profiling of chromatin accessibility and gene expression from the same single nucleus (snATAC + snRNA) to investigate the cellular heterogeneity of hundreds of thousands of bone marrow mononuclear cells (BMMCs). We employed a sequential integration strategy to construct a single-cell bimodal mini-atlas of BMMCs from both AML patients and healthy controls. Joint analysis of these modalities enabled high-resolution clustering of cell types across individuals and detailed comparative analysis of leukemic and healthy cells. This mini atlas provided two complementary perspectives on each cell simultaneously, facilitating the investigation of both intra and inter donor heterogeneity. Analyses of differentially expressed genes and differentially accessible regions revealed key molecular signatures across distinct AML subtypes. Furthermore, simultaneous transcriptomic and epigenomic profiling uncovered gene regulatory networks (GRNs) linking transcription factors, their binding sites, and target gene expression—highlighting putative regulatory elements that may contribute to disease progression and therapeutic resistance. In summary, we present the first single-cell bimodal mini-atlas of AML, providing insights into the epigenetic and transcriptional landscapes of leukemia cells. This resource offers a valuable platform for the scientific community and holds promise for informing strategies to improve patient outcomes.