Evidence map›Paper›PMID 40830365›Full record

ArticleNature communications2025

A high-resolution, nanopore-based artificial intelligence assay for DNA replication stress in human cancer cells.

Mathew J K Jones, Subash Kumar Rai, Pauline L Pfuderer, Alexis Bonfim-Melo, Julia K Pagan, Paul R Clarke, Francis Isidore Garcia Totañes, Catherine J Merrick, Sarah E McClelland, Michael A Boemo

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Mathew J K JonesFrazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia. mathew.jones@uq.edu.au.ORCID http://orcid.org/0000-0003-2714-8411
Subash Kumar RaiFrazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-3694-5586
Pauline L PfudererDepartment of Pathology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-2349-2920
Alexis Bonfim-MeloFrazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0002-7812-7701
Julia K PaganSchool of Biomedical Sciences, The University of Queensland, Saint Lucia, QLD, Australia.
Paul R ClarkeFrazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia.
Francis Isidore Garcia TotañesWellcome Sanger Institute, Cambridge, UK.ORCID http://orcid.org/0000-0002-3419-5243
Catherine J MerrickDepartment of Pathology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7583-2176
Sarah E McClellandBarts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0002-9987-4511
Michael A BoemoDepartment of Pathology, University of Cambridge, Cambridge, UK. mb915@cam.ac.uk.ORCID http://orcid.org/0000-0002-0326-8200

Funding

Isaac Newton Trust 19.39BLeverhulme Trust RPG-2022-028
6 · The paper itself

Abstract

DNA replication stress is a hallmark of cancer that is exploited by chemotherapies. Current assays for replication stress have low throughput and poor resolution whilst being unable to map the movement of replication forks genome-wide. We present a new method that uses nanopore sequencing and artificial intelligence to map forks and measure their rates of movement and stalling in melanoma and colon cancer cells treated with chemotherapies. Our method can differentiate between fork slowing and fork stalling in cells treated with hydroxyurea, as well as inhibitors of ATR, WEE1, and PARP1. These different therapies yield different characteristic signatures of replication stress. We assess the role of the intra-S-phase checkpoint on fork slowing and stalling and show that replication stress dynamically changes over S-phase. Finally, we demonstrate that this method is applicable and consistent across two different flow cell chemistries (R9.4.1 and R10.4.1) from Oxford Nanopore Technologies. This method requires sequencing on only one nanopore flow cell per sample, and the cost-effectiveness enables functional screens to determine how human cancers respond to replication-targeted therapies.

Indexed as

Artificial IntelligenceDNA ReplicationNanoporesNanopore SequencingNeoplasmsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell Line, TumorColonic NeoplasmsHumansHydroxyureaMelanomaPoly (ADP-Ribose) Polymerase-1Protein-Tyrosine KinasesS PhaseAtaxia Telangiectasia Mutated ProteinsATR protein, humanCell Cycle ProteinsHydroxyureaPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Protein-Tyrosine KinasesWEE1 protein, human

Identifiers

PMID40830365
PMCPMC12365011

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.