Fig. 5: SPRINTER reveals increased single-cell rates of clone-specific genomic variants and enrichment for specific oncogene amplifications in TNBC and HGSC high-proliferation clones.

a, In 7 TNBC and 15 HGSC tumors (dark blue and dark pink in the first row with distinct tumors colored differently in the second row), the distribution of the S fraction (bottom, y axis) of each SPRINTER clone (x axis) with varying cell numbers (top, y axis in log₁₀ scale) was calculated by bootstrapping (with 300 repeats) using the S-phase cells identified and assigned to clones by SPRINTER. b–d, Single-cell rates of clone-specific genomic variants were measured in individual cells (y axis, for 23,383 TNBC and 10,235 HGSC cells, excluding cells classified as outliers, tumors with single clones and cells without measured variants) for SNVs (b), SVs (c) and CNAs (d) in high- and low-proliferation clones (separated by the median of inferred S fractions, x axis) in the TNBC (left) and HGSC (right) datasets, with P values as measured by a one-sided Mann–Whitney U test and Cohen’s d effect sizes shown. e, For each known oncogene (dots, obtained from the COSMIC Cancer Gene Census excluding tumor suppressor genes), a one-sided Mann–Whitney U test was used to identify amplifications present in clones with significantly higher S fractions than other clones, with P values multiple hypothesis-corrected using the Benjamini–Hochberg method with family-wise error rate = 0.05 (y axis, negative log scale) and the related differences between the average S fractions (x axis) shown for each test. Genes passing the test (red, with the minimum corrected threshold indicated with the dotted line) are enriched in clones with increased proliferation, with genes relevant to cancer proliferation annotated. f, Cancer-relevant pathways (y axis) enriched for genes with amplifications significantly associated with high clone proliferation from e were identified using a gene set enrichment analysis (combined scores on x axis). In a–d, box plots show the median and the IQR with whiskers denoting values within 1.5 times the IQR from the first and third quartiles, respectively.