Speaker
Description
DNA replication duplicates the genome before cell division, and its faithful completion is essential for genome stability. Failures in this process generate replication stress, a hallmark of cancer, but also a therapeutic opportunity, since drugs that further perturb replication can push tumour cells beyond tolerable limits \cite{jones2025high}. Understanding these effects remains difficult, because experiments are costly and available data often provide only partial views of replication dynamics across the genome. Here we present a mathematical framework for genome wide DNA replication that links mechanistic modelling, inference, and therapeutic applications. The framework is based on an analogy with one dimensional crystal growth, in which stochastic origin firing and replication fork speed shape the spatiotemporal progression of replication. Within this setting, light cone formalisms and transport equations for fork densities connect replication timing, origin usage, and fork kinetics. This makes it possible to reconstruct initiation landscapes from timing data and to identify genomic regions where replication dynamics break down \cite{berkemeier2025dna}. In addition, we show that combining mechanistic modelling with genome language models and physics informed machine learning opens the way to predictive modelling of targeted therapies with translational potential for cancer biology \cite{pfuderer2026genome}.
Bibliography
@article{jones2025high,
title={A high-resolution, nanopore-based artificial intelligence assay for DNA replication stress in human cancer cells},
author={Jones, Mathew JK and Rai, Subash Kumar and Pfuderer, Pauline L and Bonfim-Melo, Alexis and Pagan, Julia K and Clarke, Paul R and Tota{\~n}es, Francis Isidore Garcia and Merrick, Catherine J and McClelland, Sarah E and Boemo, Michael A},
journal={Nature Communications},
volume={16},
number={1},
pages={7732},
year={2025},
publisher={Nature Publishing Group UK London}
}
@article{berkemeier2025dna,
title = {DNA replication timing reveals genome-wide features of transcription and fragility},
author = {Berkemeier, Francisco and Cook, Peter R and Boemo, Michael A},
journal = {Nature Communications},
volume = {16},
number = {1},
pages = {1--12},
year = {2025},
publisher = {Nature},
url = {https://www.nature.com/articles/s41467-025-59991-w},
}
@article{pfuderer2026genome,
title = {A genome language model for mapping DNA replication origins},
author = {Pfuderer, Pauline L and Berkemeier, Francisco and Nassar, Joelle and Crisp, Alastair and Jaworski, Jedrzej J. and Moore, Jessica and Sale, Julian E. and Boemo, Michael A},
journal = {bioRxiv},
pages = {2026--01},
year = {2026},
publisher = {Cold Spring Harbor Laboratory},
url = {https://www.biorxiv.org/content/10.64898/2026.01.29.702604v1},
}
