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<p>Current approaches to mapping fork progression in the human genome suffer from drastically low throughput. Here, we introduce ForkML, a nanopore sequencing-based method automatically positioning thousands of individual fork velocities by tracking BrdU incorporation into replicating DNA after double pulse-labelling of asynchronous cells. ForkML recovers known human fork speed, accurately&#xa0;detects replication stress, and, crucially, connects replication dynamics to genomic and chromatin contexts, exposing fork slowdown in early-replicating transcribed regions.</p>

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Automated mapping of DNA replication fork progression in human cells with ForkML

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月23日

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  • Victoria Rojat,
  • Diletta Ciardo,
  • Alan Tourancheau,
  • Florence Proux,
  • Etienne Jean,
  • Jean-Michel Arbona,
  • Benjamin Audit,
  • Gael A. Millot,
  • Frédéric Bonhomme,
  • Paola B. Arimondo,
  • Olivier Hyrien,
  • Benoît Le Tallec

摘要

Current approaches to mapping fork progression in the human genome suffer from drastically low throughput. Here, we introduce ForkML, a nanopore sequencing-based method automatically positioning thousands of individual fork velocities by tracking BrdU incorporation into replicating DNA after double pulse-labelling of asynchronous cells. ForkML recovers known human fork speed, accurately detects replication stress, and, crucially, connects replication dynamics to genomic and chromatin contexts, exposing fork slowdown in early-replicating transcribed regions.