Extended Data Fig. 4: Population balance analysis (PBA) and stationary optimal transport (StatOT) fate probability prediction.

Diffusion-drift modeling was used to define commitment probabilities to lineage fates for HSPCs by PBA and StatOT. (a-b) We compare the proportion of mass (as measured by fraction of total predicted hematopoietic output) by lineage and age in terminal fates for (a) PBA and (b) StatOT to the proportion of cells that reside in annotated clusters of differentiated cell types (observed probability mass). The proportion of mass derived from PBA and StatOT represent the expected proportion of cells ending up with a particular lineage fate, though individual cells may have the potential to acquire multiple fates. Agreement between observed and expected probabilities were used as a metric for evaluating performance of the probabilistic algorithms. (c) Schematic of triangle fate probability plots that serve as output from diffusion-drift modeling. Individual cell fate lineage probability is defined based on location relative to lymphoid, myeloid (including monocyte), and erythro-megakaryocytic fates. Centroid (*) indicates the expected average HSPC probability. Also displayed is color scheme for individual cells, which is based on cell type cluster category from Louvain clustering (Extended Data Fig. 3a), and is used for the remainder of Extended Data Fig. 4. (d) Individual cell lineage commitment probabilities to lymphoid, myeloid, and erythro-megakaryocytic fates for HSPCs in each age phase by population balance analysis (PBA) and stationary optimal transport (StatOT). (e) Individual cell lineage commitment probabilities for HSPCs in all 26 donors in the dataset. (f) Focusing only on the least differentiated, hematopoietic stem cell (HSC)-containing state cluster, the mean PBA and StatOT probabilities of bias towards myeloid, erythro-megakaryocytic, or lymphoid fates at each age are displayed. (g) Upon comparing the lineage fate probabilities between two age ranges, the significance of each difference was calculated using Student’s t-test, with p-value for each pair-wise comparison displayed as a heatmap.