Fig. 1: Human origin repertoire.

a Experimental workflow. SNS-seq was performed on three untransformed (hESC H9, patient derived hematopoietic cells (HC), and patient derived Human Mammary Epithelial Cells (HMEC), and three immortalised cell types (total n = 19). Immortalised cells were obtained through a reduction of TP53 mRNA levels (ImM-1, p53^KD) or further expression of oncogenes RAS (ImM-2, +RAS) or WNT (ImM-3, +WNT) in HMEC cells. b UCSC genome browser snapshot of the human replication origin (MYC origin) captured by SNS-seq. Representative SNS-seq read-profiles, published positions of ORC2- (red) and MCM7-bound (blue) regions and the GENCODE genes (v25) are shown. The positions of origins defined in this study are shown on top; red: high-activity origins (core origins), light pink: low-activity origins (stochastic origins). c Boxplot showing the average origin activity (normalised SNS-seq counts across all samples, in Log2) per each quantile (x-axis represents Q1-Q10 origins). Line within the boxplot represents median, whereas the bounds of the box define the first and third quartiles. Bottom and top of whiskers represent minimum and maximum numbers respectively for each boxplot. d Q1 and Q2 origins host the overwhelming majority of initiation events in untransformed cell types. Pie chart representing the percentage of DNA replication initiation events (normalised SNS-seq counts) that originate from Q1, Q2 or Q3-10 origins in the indicated untransformed cell types. e Density plots showing the distribution of the distances to nearest origin (x-axis, in Kb) for core origins (left panel) and stochastic origins (right panel). In grey are control density plots that show the distribution of the distances between core/stochastic origins to the nearest randomised genomic region of the same size and number as origins. Both frequency plots were significantly different from randomised distributions (p ≤ 2.2E-16, Chi-square Goodness-of-Fit test in R with observed and expected values for frequency).