Clinical Trial Simulation of HMA Treatment in MDS Patients Based on Gene Signature Rules. A genomically-informed computational method identified 3 MDS genomic signatures with potential to predict HMA treatment response based on a training set of patient data (N=80). A separate validation cohort of 109 patients was then virtually recruited into one of 3 HMA treatment arms based on genomic signature rules. In this study, patients with TET2 mutation alone (red line) showed a trend toward greater clinical response than the unselected control cohort (black line) (P=0.08). However, patients harboring TET2 mutation without mutations of ASXL1, SRSF2, and EZH2 (green line) showed significantly greater response to HMA treatment than the unselected control cohort (black line) (p=0.0023).