High-resolution single-molecule replication profiling of the human genome

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.

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BibTeX RIS

BibTeX

@misc{tourancheau2026highresolution,
  title = {{High-resolution single-molecule replication profiling of the human genome}},
  author = {Alan Tourancheau and Victoria Rojat and Diletta Ciardo and Florence Proux and Laurent Lacroix and Jean-Michel Arbona and Benjamin Audit and Olivier Hyrien and Benoît Le Tallec},
  howpublished = {HAL},
  year = {2026},
  month = jul,
  doi = {10.64898/2026.07.15.738623},
  url = {https://hal.science/hal-05844589v1},
  note = {CC BY 4.0},
}

RIS

TY  - UNPB
TI  - High-resolution single-molecule replication profiling of the human genome
AU  - Alan Tourancheau
AU  - Victoria Rojat
AU  - Diletta Ciardo
AU  - Florence Proux
AU  - Laurent Lacroix
AU  - Jean-Michel Arbona
AU  - Benjamin Audit
AU  - Olivier Hyrien
AU  - Benoît Le Tallec
PY  - 2026
DA  - 2026/07/20
PB  - HAL
DO  - 10.64898/2026.07.15.738623
UR  - https://hal.science/hal-05844589v1
AB  - 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.
ER  -

Abstract

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