Fig. 2

Pseudotime analysis uncovers a PRKD2-centred malignant branch. (A,B) Monocle2 principal graph of 2137 plasma cells (red = normal, cyan = MM-malignant). Branch nodes ① and ② split a quiescent upper arm from a malignant lower arm. (C) Same graph by clinical stage. Cells shift from root (HD) through MGUS and SMM to populate the malignant arm in MM; grey curves show stage-specific density along pseudotime. (D) Gene-smooths along pseudotime. Early regulators (BTG2, FOS/FOSB, CD79A) wane, ribosome/secretory genes (IGHG, IGHD/M, RPL29, RPS5/A) rise. PRKD2 climbs steadily, peaking where malignant cells accumulate. (E) BEAM heat-map of 278 branch genes. Module 1—up-regulated in malignant fate—contains PRKD2 with ribosome/ER genes (RPS5, RPL29); modules 2–4 house stress, Ig heavy- and light-chain signatures, respectively. BEAM analysis was performed with Monocle 2 [v2.3] (http://cole-trapnell-lab.github.io/monocle-release/) and the heat-map rendered in R [v4.3.3] using ComplexHeatmap [v2.1] (https://bioconductor.org/packages/ComplexHeatmap).