High-resolution single-molecule replication profiling of the human genome
Year: 2026
Type: preprint
Abstract: Despite the considerable progress made in recent years thanks to the rise of long-read sequencing, high-resolution, single molecule (SM)-based replication profiling of large genomes has remained out of reach. Here, we present a replication labelling strategy consisting in repeated pulse-labelling of asynchronously growing cells with the thymidine analogue bromodeoxyuridine (BrdU) that greatly enhances the number of detectable replication tracks. We show that the ‘multipulse’ BrdU labelling protocol, in association with ForkML, a machine-learning method translating BrdU signals in nanopore reads into oriented and positioned replication forks, enables the establishment of a SM replication map of the entire human genome at kilobase resolution.
Institutions: Centre National de la Recherche Scientifique, Inserm, Université Paris Sciences et Lettres, École Normale Supérieure - PSL, Institut de Biologie de l'École Normale Supérieure, Institut de Biologie du Développement Marseille, École Normale Supérieure de Lyon, Laboratoire de Physique de l'ENS de Lyon
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7169826253