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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
...number of genomic mutations in just a few cell cycles. In contrast, despite clear deaminase activity and DNA damage, APOBEC3B upregulation does not generate a significant increase in mutations in the gastric epithelium. APOBEC3B-associated mutagenesis remains minimal even in the context of TP53...
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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
...-delta and/or Pol-zeta). A summary of the roles of Ung1, HR-dependent lesion bypass, and TLS can be found in Supplemental Fig. S1A. Although we have not found alternate mechanisms that prevent APOBEC-induced mutagenesis, we reason they may exist for cells showing replication or transcriptional stress...
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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...as enhancers: CREs distal to transcription start sites (TSSs) that regulate the cell type specificity of gene expression. However, few cCREs have been evaluated for their endogenous function, their target gene, or their roles in conditions of stress (May et al. 2012).Many key developmental factors...
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Research: Multisite long-read sequencing reveals the early contributions of somatic structural variations to HBV-related hepatocellular carcinoma tumorigenesis
- Tianfu Zeng,
- Haotian Liao,
- Lin Xia,
- Siyao You,
- Yanqun Huang,
- Jiaxun Zhang,
- Yahui Liu,
- Xuyan Liu,
- and Dan Xie
Genome Res. April 2025 35: 671-685; Published in Advance March 4, 2025, doi:10.1101/gr.279617.124
...of HCC. Long-read RNA sequencing reveals that some HBV-induced SVs impact cancer-associated genes, with TRAs being capable of inducing the formation of fusion genes. These findings enhance our understanding of somatic SVs in HCC and their role in early tumorigenesis.As the most prevalent form of primary...
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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
..., many of which were shared among subsets of cells within and between cell types. Perturbed cells continued to express cell type–specific markers, simultaneously maintaining their respective identities while adopting a more general signature of oxidative stress (Supplemental Fig. S4C). This suggests...
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Research: Mutability of mononucleotide repeats, not oxidative stress, explains the discrepancy between laboratory-accumulated mutations and the natural allele-frequency spectrum in C. elegans
- Moein Rajaei,
- Ayush Shekhar Saxena,
- Lindsay M. Johnson,
- Michael C. Snyder,
- Timothy A. Crombie,
- Robyn E. Tanny,
- Erik C. Andersen,
- Joanna Joyner-Matos,
- and Charles F. Baer
Genome Res. September 2021 31: 1602-1613; Published in Advance August 17, 2021, doi:10.1101/gr.275372.121
...laboratory mutation accumulation (MA) experiments and the standing site-frequency spectrum, which has been argued to be in part owing to increased oxidative stress in the laboratory environment. Using sequence data from C. elegans MA lines carrying a mutation (mev-1) that increases the cellular titer...
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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
...for cell viability under normal conditions (Chang et al. 2020a), as well as for screening resistance genes for both biotic and nonbiotic stresses (Liu et al. 2021). However, the application of such powerful -scale mutagenesis systems at the whole-animal level in nonmodel organisms has been unsuccessful...
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Research: Modest increase in the de novo single-nucleotide mutation rate in house mice born by assisted reproduction
- Laura Blanco-Berdugo,
- Alexis Garretson,
- and Beth L. Dumont
Genome Res. January 2026 36: 50-60; Published in Advance November 13, 2025, doi:10.1101/gr.281180.125
...transfer) affects stability. Age-matched cohorts of 12 ART-derived and 16 naturally conceived C57BL/6J inbred mice were reared in a controlled setting and whole--sequenced to ∼50× coverage. Using a rigorous pipeline for de novo single-nucleotide variant (dnSNV) discovery, we observe a ∼30% (95% CI: 4...
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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
...of Drosophila melanogaster (Muller 1928; Bateman 1959; Mukai 1964) and in humans by pedigree analysis (for review, see Nachman 2004). In recent decades, DNA sequencing techniques have greatly enhanced the ability to detect new mutations, allowing the estimation of mutation rates at the molecular level (Halligan...
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Method: Enhancing nanopore adaptive sampling for PromethION using readfish at scale
- Rory Munro,
- Alexander Payne,
- Nadine Holmes,
- Chris Moore,
- Inswasti Cahyani,
- and Matthew Loose
Genome Res. April 2025 35: 877-885; Published in Advance January 30, 2025, doi:10.1101/gr.279329.124
...These authors contributed equally to this work. Corresponding author: matt.loose@nottingham.ac.ukAbstractA unique feature of Oxford Nanopore Technologies sequencers, adaptive sampling, allows precise DNA molecule selection from sequencing libraries. Here, we present enhancements to our tool, readfish, enabling...
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