(A) Patient characteristics of the discovery and validation cohorts. Values are expressed as n, median (interquartile range) or n (%), unless otherwise stated. mPAP mmHg: Mean pulmonary arterial pressure mmHg; mRAP mmHg: Mean right atrial pressure mmHg; PAWP mmHg: Pulmonary arterial wedge pressure mmHg; PVR wood: Pulmonary vascular resistance Wood units; TPR wood: Total pulmonary resistance Wood units; 6MWD: 6-min walk distance; NT-pro BNP: N-terminal pro-brain natriuretic peptide. The t-test was performed for statistical analysis, except age at diagnosis were analyzed by ANOVA test and Chi-Squared test was used for gender comparison. (B) Principal component analysis on the RNA modification data. PC1: the first principal component; PC2: the second principal component. Each dot represents one human subject in the discovery cohort. (C) The RNA modification signature. (D) Comparison of the RNA modification index among the control, Group 1 PH, and Group 3 PH subjects in the discovery cohort. Mean ± standard deviation: −6.48±1.60 for control, −0.83±3.90 for Group 1 PH, and 10.84±0.84 for Group 3 PH. (E) Comparison of the RNA modification index among the control, Group 1 PH, and Group 3 PH subjects in two validation cohorts. Mean ± standard deviation: −3.90±4.16 for control, 0.48±2.72 for Group 1 PH, and 6.19±5.41 for Group 3 PH in VAL1 and −5.22±4.09 for control, −0.43±5.71 for Group 1 PH, and 4.39±6.41 for Group 3 PH in VAL2. (F) The ROC curve of the RNA modification index in distinguishing between the PH and control subjects, between the Group 3 PH and control subjects, and between the Group 3 PH patients and other subjects (controls and Group 1 subjects) in the validation cohorts. The light blue area indicates the confidence interval of the ROC curve. VAL1: the first validation cohort; VAL2: the second validation cohort.