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

Rojat, Victoria; Ciardo, Diletta; Tourancheau, Alan; Proux, Florence; Jean, Etienne; Arbona, Jean-Michel; Audit, Benjamin; Millot, Gael A et al. · Nat Commun · 2026

basic_science · Level V

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Abstract

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.

Medical subject headings