Supplementary Figure S2 from Integrated genomic and transcriptomic analysis improves disease classification and risk stratification of MDS with ring sideroblasts.

Clonal hierarchy analysis of SF3B1-SRSF2 co-mutated cases. A. Results from the hierarchical rank analysis of mutations detected by DNAseq in the 4 cases harboring both SF3B1 and SRSF2 mutation using Pyclone. The analysis was also performed using DPClust, which provided converging results (data not shown). Tumor cell fraction (axes) for each detected clone and its 95% confidence interval (dot size) is represented in a scatter-plot, using different color according to the cluster driving mutation (SF3B1, red; SRSF2, blue; other drivers, gray). SF3B1 dominancy in MDS392 and MDS 640, together with the SRSF2 large clone size are suggestive of both splicing factor mutations in the same clone. On the contrary, MDS694 and MDS965 had a dominant SF3B1 clone associated with a very little and probably independent SRSF2 secondary clone. B. Results from single-cell derived colony-forming unit (CFU) genotyping confirming the concurrent double splicing factor mutations within the same clone in patient MDS382 and MDS640. CFU experiment was not carried out for the other two cases because of the very low probability of SF3B1/SRSF2 double positive clone identification, as already suggested by current data in the literature related to the presence of SF3B1K700E mutation (ref. 1).