Fig. 2: Clinical and molecular determinants of cellular heterogeneity in MF.

A Outline of the integrative pharmacoscopy and clinical proteotyping workflow of MF patients as performed in this study. B Circos plot of clinical annotations of the MF PBMC cohort. Legend indicates color codes for the included variables. For discrete variables, patient numbers are included, and for continuous variables, the range and median are represented. Proteotyping outliers are annotated by H and T for HSPC and T-cell proteotypes, respectively. See also Supplementary Data 1. C Cell population sizes as defined by the CNN-based cell classifier across the DMSO-treated conditions of the MF PBMC cohort. Annotations indicate the mutation status and PB blast counts of the respective patients. D t-SNE embedding of the CNN class probabilities for DMSO-treated cells across the cohort of 43 MF patients (n = 41,286 patient cells; up to 250 cells randomly selected from HSPC, T-cell, monocyte, and other cells for each MF patient). Top left panel: CNN-based cell types. Top right panels: single-cell CALRm (upper) and pSTAT5 (lower) intensities, scaled by z-score normalization. Bottom panels: single-cell CD3/CD14 and CD34 intensities and nuclear area. E CALRm/pSTAT5 intensities per cell type and driver mutation. Intensities are scaled by z-score normalization per patient. Boxplots indicate the range of scaled intensities across MF CALR and JAK2 patients, and dots represent individual patient values (MF CALR, n = 14; MF JAK2, n = 26). Fill colors indicate cell types as in Fig. 1C. F CALRm intensities per cell type and homozygous (VAF > = 75%) or heterozygous MF CALR (VAF < 75%). Intensities are scaled by z-score normalization across all MF CALR cells (MF CALR heterozygous, n = 11; MF CALR homozygous, n = 3). Boxplots indicate the range of scaled intensities, and dots represent individual patient values. Fill colors indicate cell types as in Fig. 1C. Asterisks indicate non-adjusted two-sided Student’s t-test significance: **** = p < 0.0001, *** = p < 0.001, ** = p < 0.01, * = p < 0.05; exact p-values are reported in Source Data. Boxplots as in Fig. 1A. See also Supplementary Fig. 2.