Extended Data Fig. 2: Distribution of oxidative DNA damage hotspots.

a, Heatmaps showing the reads densities on DNA damage hotspots from cells with treatment of varying concentrations of H₂O₂. b, Experiment design of H₂O₂ treatment on HeLa cells. c, Uniform manifold approximation and projection (UMAP) embedding showing single cells based on Paired-Damage-seq DNA profiles. Each dot represents an individual nucleus profiled by Paired-Damage-seq and is colored according to the treatment conditions. d, Weighted gene co-expression network analysis (hdWGCNA) dendrograms for the co-expression networks constructed. e, Module eigengene as a function of pseudotime for the representative co-expression module M1 (with decreased expression levels) and M3 (with increased expression levels). The solid lines represent LOESS (locally estimated scatterplot smoothing) regression fits, with the shaded areas indicating the 95% confidence intervals. f, The enriched GO Terms for co-expression module M1 and M3. g, Violin plots showing the average detected signal levels in compartments A and B (RPKM, in 250-kb non-overlapping bins) for DNA damage, non-targeting tagmentation control and ATAC-seq signals of HeLa cells; for all box plots, hinges were drawn from the 25th to 75th percentiles, with the middle line denoting the median, whiskers denoting a maximum 2× the interquartile range and outliers indicated with dots; n = 5,495 (Compartment A) and 4,593 (Compartment B). h, Line plots showing the DNA damage signals around genic regions of genes with different expression levels. i, Barplots showing the numbers of DNA damage peaks in control and H₂O₂ treated HeLa cells. j, Barplots showing the relative enrichments of DNA damage peaks of control and H₂O₂ treated HeLa cells in different genomic regions. k, Upset plots showing the intersection size of damage peaks in untreated and H₂O₂ treated HeLa cells. The non-targeting tagmentation control is also shown for comparison.

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