Genome replication mapping methods profile cell populations, masking cell-to-cell heterogeneity. Here, we describe FORK-seq, a nanopore sequencing method to map replication of single DNA molecules at 200-nucleotide resolution. By quantifying BrdU incorporation along pulse-chased replication intermediates from Saccharomyces cerevisiae, we orient 58,651 replication tracks reproducing population-based replication directionality profiles and map 4964 and 4485 individual initiation and termination events, respectively. Although most events cluster at known origins and fork merging zones, 9% and 18% of initiation and termination events, respectively, occur at many locations previously missed. Thus, FORK-seq reveals the full extent of cell-to-cell heterogeneity in DNA replication.

中文翻译：

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FORK-seq：通过纳米孔测序观察酿酒酵母基因组的复制情况


基因组复制作图方法描绘细胞群，掩盖细胞间的异质性。在这里，我们描述了 FORK-seq，一种纳米孔测序方法，以 200 个核苷酸的分辨率绘制单个 DNA 分子的复制图。通过量化沿着酿酒酵母的脉冲追踪复制中间体的 BrdU 掺入，我们定位了 58,651 个复制轨迹，以复制基于群体的复制方向性概况，并分别绘制了 4964 个和 4485 个个体起始和终止事件。尽管大多数事件聚集在已知的起源和分叉合并区域，但 9% 和 18% 的起始事件和终止事件分别发生在许多以前错过的位置。因此，FORK-seq 揭示了 DNA 复制中细胞间异质性的全部范围。