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Research: APOBEC3A drives deaminase mutagenesis in human gastric epithelium
- Yohan An,
- Ji-Hyun Lee,
- Joonoh Lim,
- Jeonghwan Youk,
- Seongyeol Park,
- Ji-Hyung Park,
- Kijong Yi,
- Taewoo Kim,
- Chang Hyun Nam,
- Won Hee Lee,
- Soo A Oh,
- Yoo Jin Bae,
- Thomas M. Klompstra,
- Haeun Lee,
- Jinju Han,
- Junehwak Lee,
- Jung Woo Park,
- Jie-Hyun Kim,
- Hyunki Kim,
- Hugo Snippert,
- Bon-Kyoung Koo,
- and Young Seok Ju
Genome Res. October 2025 35: 2158-2172; Published in Advance August 26, 2025, doi:10.1101/gr.280338.124
...APOBEC-induced DNA damage, such as replication stalling or double-strand breaks (DSBs), as previously reported (Fig. 1G,H; Supplemental Fig. S5; Burns et al. 2013; Green et al. 2016).APOBEC3A, not APOBEC3B, induces genomic mutationsTo assess the mutagenic impacts of A3A and A3B, we investigated acquired...
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Research: Genetic inhibitors of APOBEC3B-induced mutagenesis
- Tony M. Mertz,
- Elizabeth Rice-Reynolds,
- Ly Nguyen,
- Anna Wood,
- Cameron Cordero,
- Nicholas Bray,
- Victoria Harcy,
- Rudri K. Vyas,
- Debra Mitchell,
- Kirill Lobachev,
- and Steven A. Roberts
Genome Res. September 2023 33: 1568-1581; Published in Advance August 2, 2023, doi:10.1101/gr.277430.122
....mertz@wsu.edu and steven.roberts2@wsu.edu; srober23@uvm.eduAbstractThe cytidine deaminases APOBEC3A (A3A) and APOBEC3B (A3B) are prominent mutators of human cancer s. However, tumor-specific genetic modulators of APOBEC-induced mutagenesis are poorly defined. Here, we used a screen to identify 61 gene deletions...
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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
...to UV mutagenesis. However, the impact of genomic context and chromatin architecture on CPD deamination rates in cells remains poorly understood. Here, we develop a method known as dCPD-seq to map deaminated CPDs (dCPDs) across the of repair-deficient yeast cells at single-nucleotide resolution. Our d...
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Method: High-throughput and genome-scale targeted mutagenesis using CRISPR in a nonmodel multicellular organism, Bombyx mori
- Sanyuan Ma,
- Tong Zhang,
- Ruolin Wang,
- Pan Wang,
- Yue Liu,
- Jiasong Chang,
- Aoming Wang,
- Xinhui Lan,
- Le Sun,
- Hao Sun,
- Run Shi,
- Wei Lu,
- Dan Liu,
- Na Zhang,
- Wenbo Hu,
- Xiaogang Wang,
- Weiqing Xing,
- Ling Jia,
- and Qingyou Xia
Genome Res. January 2024 34: 134-144; Published in Advance January 8, 2024, doi:10.1101/gr.278297.123
...of mutant lines identified a large set of genes responsible for visual phenotypic or economically valuable trait changes. Next, we performed pooled context-specific positive screens for tolerance to environmental pollutant cadmium exposure, and identified KWMTBOMO12902 as a strong candidate gene...
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Research: The rate and spectrum of new mutations in mice inferred by long-read sequencing
- Eugenio López-Cortegano,
- Jobran Chebib,
- Anika Jonas,
- Anastasia Vock,
- Sven Künzel,
- Peter D. Keightley,
- and Diethard Tautz
Genome Res. January 2025 35: 43-54; Published in Advance December 2, 2024, doi:10.1101/gr.279982.124
...for Evolutionary Biology, 24306 Plön, Germany Corresponding author: elcortegano@protonmail.comAbstractAll forms of genetic variation originate from new mutations, making it crucial to understand their rates and mechanisms. Here, we use long-read sequencing from Pacific Biosciences (PacBio) to investigate de novo...
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Research: Global characterization of somatic mutations and DNA methylation changes during vegetative propagation in strawberries
- Shaoqiang Hu,
- Xiangguo Zeng,
- Yuguo Liu,
- Yongping Li,
- Minghao Qu,
- Wen-Biao Jiao,
- Yongchao Han,
- and Chunying Kang
Genome Res. October 2024 34: 1582-1594; Published in Advance October 15, 2024, doi:10.1101/gr.279378.124
....71%–8.03%) in regenerated plants, and hypoCG-DMRs are more heritable after sexual reproduction. A high-quality haplotype-resolved is assembled for the strawberry cultivar “Beni hoppe.” The 12 “Beni hoppe” individuals randomly selected from different locations show 4731–6005 mutations relative to the reference...
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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...topic modeling, which reveals context-specific gene regulation linked to dynamic cellular processes and environmental responses, offering a deeper understanding of how gene regulation is modulated in the brain. These findings underscore the importance of genotype-environment interactions in genetic...
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Research: Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis
- Olga M. Sigalova,
- Mattia Forneris,
- Frosina Stojanovska,
- Bingqing Zhao,
- Rebecca R. Viales,
- Adam Rabinowitz,
- Fayrouz Hammal,
- Benoît Ballester,
- Judith B. Zaugg,
- and Eileen E.M. Furlong
Genome Res. May 2025 35: 1138-1153; Published in Advance April 15, 2025, doi:10.1101/gr.279652.124
...by 30%–50%. This fine-grained “mutagenesis” can reconstruct functionalized binding motifs for all factors. To prioritize causal variants, we trained a convolutional neural network (Basenji) to accurately predict binding from DNA sequence. The model can also predict measured allelic imbalance for strong...
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Research: Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations
- Alicja Pacholewska,
- Matthias Lienhard,
- Mirko Brüggemann,
- Heike Hänel,
- Lorina Bilalli,
- Anja Königs,
- Felix Heß,
- Kerstin Becker,
- Karl Köhrer,
- Jesko Kaiser,
- Holger Gohlke,
- Norbert Gattermann,
- Michael Hallek,
- Carmen D. Herling,
- Julian König,
- Christina Grimm,
- Ralf Herwig,
- Kathi Zarnack,
- and Michal R. Schweiger
Genome Res. November 2024 34: 1832-1848; Published in Advance September 13, 2024, doi:10.1101/gr.279327.124
...(LRTS) and combined complementary data derived from MDS and CLL patients with isogenic cell lines.ResultsLong-read RNA-seq expands patient transcriptome landscapes in divergent biological contextsTo investigate the effect of SF3B1 mutations on splicing, we characterized the transcriptomes of three data...
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Research: Oxidative stress accelerates intestinal tumorigenesis by enhancing 8-oxoguanine-mediated mutagenesis in MUTYH-deficient mice
- Mizuki Ohno,
- Noriko Takano,
- Kyoko Hidaka,
- Fumiko Sasaki,
- Kazumi Yamauchi,
- Yasunobu Aoki,
- Takehiko Nohmi,
- Yusaku Nakabeppu,
- Yoshimichi Nakatsu,
- and Teruhisa Tsuzuki
Genome Res. January 2024 34: 47-56; Published in Advance January 30, 2024, doi:10.1101/gr.278326.123
..., we concluded that 8-oxoG:A is the key molecular initiating event triggering intestinal tumorigenesis in Mutyh−/− mice. Moreover, sequence context–dependent G:C > T:A mutagenesis yielded biased amino acid change to missense and stop-gain mutations (Supplemental Fig. S9). Our results and human MAP...

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