Application of CASCADE in modeling tumor evolution
(A) Projection of longitudinal samples (n = 23) from the 11 patients in the single-cell discovery cohort into the lineage-ecological space. Only samples with both detectable malignant and non-malignant cells were included in this plot.
(B) Sankey plot of transitions in the lineage-ecological space between the baseline and the final post-treatment sample of each patient in the single-cell discovery cohort (n = 8). Patients with only one sample in (A) are not included in this plot.
(C) Projection of longitudinal samples (n = 75) from liver cancer patients in the NCI CLARITY retrospective cohort into the lineage-ecological space. Patients may have more than one baseline or post-treatment sample.
(D) Sankey plot of transitions in the lineage-ecological space between the baseline and the final post-treatment sample of each patient in the NCI CLARITY retrospective cohort (n = 32 patients). Only patients with at least two samples are included here.
(E) Kaplan-Meier plot of the patients in the NCI CLARITY retrospective cohort based on quadrants of the baseline samples (A1, n = 13 patients; A2, n = 5; B1, n = 6; B2, n = 8). The p value was calculated using the log rank test for trend.
(F) Forest plot of the hazard ratio in all patients from the NCI CLARITY retrospective cohort (n = 32). Patients are grouped by their lineage-ecological quadrant at baseline (left) (A1, n = 13 patients; A2, n = 5; B1, n = 6; B2, n = 8) and their final follow-up time point (right) (A1, n = 13 patients; A2, n = 6; B1, n = 5; B2, n = 8). Quadrant B2 was used as the reference group for hazard ratio calculation. Bars show 95% confidence interval. ∗p < 0.05 for baseline A1 or A2 compared with baseline B2; p < 0.05 for follow-up A2 compared with follow-up B2; p > 0.05 for follow-up A1 or B2 compared with follow-up B2.
(G) Forest plot of the hazard ratio in HCC patients from the NCI CLARITY retrospective cohort (n = 18). Patients are grouped by their lineage-ecological quadrant at baseline (left) (A1, n = 11 patients; A2, n = 5; B1, n = 1; B2, n = 1) and their final follow-up time point (right) (A1, n = 9 patients; A2, n = 6; B1, n = 1; B2, n = 2). Quadrant B2 was used as the reference group for hazard ratio calculation. Bars show 95% confidence interval. p < 0.05 for baseline A1 or A2 compared with B2; p > 0.05 for baseline B1 compared with baseline B2; p < 0.05 for follow-up A2 compared with follow-up B2; p > 0.05 for follow-up A1 or B1 compared with follow-up B2. See also Figures S7 and S8 and Table S5.