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Research: Characterization of the role of spatial proximity of DNA double-strand breaks in the formation of CRISPR-Cas9-induced large structural variations
- Mikkel Dahl-Jessen,
- Thorkild Terkelsen,
- Rasmus O. Bak,
- and Uffe Birk Jensen
Genome Res. February 2025 35: 231-241; Published in Advance January 13, 2025, doi:10.1101/gr.278575.123
...diversity, evolution, and carcinogenesis and are, as such, important for human health. However, it remains unclear how spatial proximity of double-strand breaks (DSBs) affects the formation of SVs. To investigate if spatial proximity between two DSBs affects DNA repair, we used data from 3C experiments (Hi...
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Resource: A systems view on DNA damage response kinetics in Tetrahymena
- Emily Nischwitz,
- Vivien Schoonenberg,
- Rachel Mullner,
- Albert Fradera-Sola,
- Susanne Zimbelmann,
- Joshua J Smith,
- and Falk Butter
Genome Res. January 28, 2026 gr.281000.125; Published in Advance January 28, 2026, doi:10.1101/gr.281000.125
...macronucleus (MAC), and a transcriptionally silent micronucleus (MIC). 68 During sexual reproduction, the new MAC chromosomes undergo ~200 regulated double-69 stranded DNA breaks and endoreplication, resulting in ~90 copies of ~180 chromosomes 70 (Loidl 2021; Zhou et al. 2022). These fascinating...
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Method: Characterization of meiotic recombination intermediates through gene knockouts in founder hybrid mice
- Benjamin Davies,
- Gang Zhang,
- Daniela Moralli,
- Samy Alghadban,
- Daniel Biggs,
- Chris Preece,
- Peter Donnelly,
- and Anjali Gupta Hinch
Genome Res. November 2023 33: 2018-2027; Published in Advance November 17, 2023, doi:10.1101/gr.278024.123
...Genomics PLC, Oxford OX1 1JD, United Kingdom ↵4 These authors equally contributed to this work. Corresponding author: anjali.hinch@well.ox.ac.ukAbstractMammalian meiotic recombination proceeds via repair of hundreds of programmed DNA double-strand breaks, which requires choreographed binding of RPA, DMC1...
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Method: Genome-wide maps of CPD deamination in yeast reveal the impact of DNA sequence context and nucleosome architecture on cytosine deamination rates
- Marian F. Laughery,
- Bastian Stark,
- Benjamin Morledge-Hampton,
- Steven A. Roberts,
- and John J. Wyrick
Genome Res. January 2026 36: 183-196; Published in Advance December 9, 2025, doi:10.1101/gr.280384.124
...sequences, both in UV-irradiated yeast cells and in human skin cancers. CPD deamination is suppressed near the transcription start and end sites of yeast genes, which may in part by mediated by DNA-bound transcription factors. Finally, we show that the wrapping of DNA in nucleosomes modulates CPD...
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Method: Spatial domain detection using contrastive self-supervised learning for spatial multi-omics technologies
- Jianing Yao,
- Jinglun Yu,
- Brian Caffo,
- Stephanie C. Page,
- Keri Martinowich,
- and Stephanie C. Hicks
Genome Res. July 2025 35: 1621-1632; Published in Advance May 20, 2025, doi:10.1101/gr.279380.124
...expression and an immunofluorescence image measuring γH2AX, a protein involved in DNA repair. The resulting predicted spatial domains from Proust were compared to other methods—GraphST, SpaGCN, and STAGATE—that employ graph convolutional neural networks (Supplemental Fig. S2). In one of the CK-p25 mouse...
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Research: Cell-type- and chromosome-specific chromatin landscapes and DNA replication programs of Drosophila testis tumor stem cell–like cells
- Jennifer A. Urban,
- Daniel Ringwalt,
- John M. Urban,
- Wingel Xue,
- Ryan Gleason,
- Keji Zhao,
- and Xin Chen
Genome Res. January 2026 36: 83-101; Published in Advance December 10, 2025, doi:10.1101/gr.280809.125
...Cell-type- and chromosome-specific chromatin landscapes and DNA replication programs of Drosophila testis tumor stem cell–like cells Jennifer A. Urban1, Daniel Ringwalt1, John M. Urban2,3, Wingel Xue1,5, Ryan Gleason1, Keji Zhao4 and Xin Chen1,2 1Department of Biology, The Johns Hopkins University...
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Method: Delineating yeast cleavage and polyadenylation signals using deep learning
- Emily Kunce Stroup and
- Zhe Ji
Genome Res. July 2024 34: 1066-1080; Published in Advance June 24, 2024, doi:10.1101/gr.278606.123
....ji@northwestern.eduAbstract3′-end cleavage and polyadenylation is an essential process for eukaryotic mRNA maturation. In yeast species, the polyadenylation signals that recruit the processing machinery are degenerate and remain poorly characterized compared with the well-defined regulatory elements in mammals. Here we...
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Method: k-mer manifold approximation and projection for visualizing DNA sequences
- Chengbo Fu,
- Einari A. Niskanen,
- Gong-Hong Wei,
- Zhirong Yang,
- Marta Sanvicente-García,
- Marc Güell,
- and Lu Cheng
Genome Res. May 2025 35: 1234-1246; Published in Advance April 10, 2025, doi:10.1101/gr.279458.124
.... The Streptococcus pyogenes Cas9 (SpCas9) protein will make a double-stranded break (DSB) at 3 nucleotides (nt) upstream of the PAM, after that the broken DNAs are ligated by non-homologous end-joining (NHEJ), which leads to different DNA editing results (mainly random small indels). Another cellular repair...
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Method: Aberrant landscapes of maternal meiotic crossovers contribute to aneuploidies in human embryos
- Daniel Ariad,
- Svetlana Madjunkova,
- Mitko Madjunkov,
- Siwei Chen,
- Rina Abramov,
- Clifford Librach,
- and Rajiv C. McCoy
Genome Res. January 2024 34: 70-84; Published in Advance December 1, 2023, doi:10.1101/gr.278168.123
..., a change in the count along the chromosome indicates the position of a meiotic crossover, that is, an exchange of DNA segments between nonsister chromatids during prophase I of meiosis. Similarly, a pair of half-siblings allows us to contrast the crossovers in either the paternal or the maternal homologs...
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Method: Deciphering context-specific gene programs from single-cell and spatial transcriptomics data with DeCEP
- Lin Li,
- Xianbin Su,
- and Ze-Guang Han
Genome Res. October 2025 35: 2300-2315; Published in Advance August 21, 2025, doi:10.1101/gr.279689.124
.... Recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) technologies have empowered the comprehensive characterization of gene programs at both single-cell and spatial resolutions. Here, we present DeCEP, a computational framework designed to characterize context...

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