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Research: Alternative splicing generates HER2 isoform diversity underlying antibody–drug conjugate resistance in breast cancer
- Gabriela D.A. Guardia,
- Carlos H. dos Anjos,
- Aline Rangel-Pozzo,
- Filipe F. dos Santos,
- Alexander Birbrair,
- Paula F. Asprino,
- Anamaria A. Camargo,
- and Pedro A.F. Galante
Genome Res. September 2025 35: 1942-1958; Published in Advance July 15, 2025, doi:10.1101/gr.280304.124
...splicing isoforms, (2) in silico characterization of HER2 protein variants, (3) HER2 isoform expression profiling by breast cancer subtype, (4) analysis of antibody–drug conjugate (ADC) sensitivity across HER2 isoform profiles, and (5) examination of HER2 isoform switches in ADC-induced resistance. (B) RNA...
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Research: Rates and spectra of de novo structural mutations in Chlamydomonas reinhardtii
- Eugenio López-Cortegano,
- Rory J. Craig,
- Jobran Chebib,
- Eniolaye J. Balogun,
- and Peter D. Keightley
Genome Res. January 2023 33: 45-60; Published in Advance December 12, 2022, doi:10.1101/gr.276957.122
..., and genetic disease, including cancers. Sequencing of mutation accumulation (MA) lines has provided estimates of rates and spectra of single-nucleotide and indel mutations in many species, yet the rate of new SMs is largely unknown. Here, we use long-read sequencing to determine the full mutation spectrum...
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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
...; Supplemental Fig. 5). We conclude that the observed differences in mutation burden between ART and naturally conceived offspring cannot be explained by cohort-specific technical artifacts.No difference in mutation spectra between naturally conceived and ART-derived miceExposure to specific environmental...
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Research: Colibactin leads to a bacteria-specific mutation pattern and self-inflicted DNA damage
- Emily Lowry,
- Yiqing Wang,
- Tal Dagan,
- and Amir Mitchell
Genome Res. August 2024 34: 1154-1164; Published in Advance August 16, 2024, doi:10.1101/gr.279517.124
...is the same in bacteria using mutation accumulation experiments with repeated exposure to colibactin producers. Ampicillin-resistant DNA damage reporter cells were cocultured for 24 h with genetically engineered colibactin producers and spotted on selective agar. A single reporter colony was then grown...
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Research: Integration site-dependent HIV-1 promoter activity shapes host chromatin conformation
- Jack A. Collora and
- Ya-Chi Ho
Genome Res. June 9, 2023 gr.277698.123; Published in Advance June 9, 2023, doi:10.1101/gr.277698.123
...that recruits additional transcriptional factors to the 11 integration locus, increases chromatin accessibility, changes 3D chromatin interactions, and enhances both 12 retroviral and host gene expression. We used 4 well-characterized HIV-1-infected cell line clones having 13 unique integration sites and low...
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Research: Hydra has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype
- Arne Sahm,
- Konstantin Riege,
- Marco Groth,
- Martin Bens,
- Johann Kraus,
- Martin Fischer,
- Hans Kestler,
- Christoph Englert,
- Ralf Schaible,
- Matthias Platzer,
- and Steve Hoffmann
Genome Res. December 2024 34: 2217-2228; Published in Advance December 4, 2024, doi:10.1101/gr.279025.124
...of mitoses—14,292 and 4605 for I cells and E cells, respectively. (C) Mutation spectra in Hydra of the three I cells and three E cells compared to literature data for human and mouse dermal fibroblasts (Milholland et al. 2017).Potential error sources are unlikely to affect the order of magnitude...
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Resource: Cell type–specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease
- Yunxiao Ren,
- Ming Hu,
- Yang E. Li,
- Andrew A. Pieper,
- Jeffrey Cummings,
- and Feixiong Cheng
Genome Res. March 2026 36: 645-659; Published in Advance January 21, 2026, doi:10.1101/gr.280436.125
...Cell type–specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease Yunxiao Ren1,2, Ming Hu3,4, Yang E. Li5, Andrew A. Pieper6,7,8,9,10,11, Jeffrey Cummings12 and Feixiong Cheng1,2,4,13 1Cleveland Clinic Genome Center, Cleveland Clinic Research...
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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
..., and the mutation frequency varies among the subs. Our study has systematically characterized the genetic and epigenetic variants in regenerated woodland strawberry plants and different individuals of the same strawberry cultivar, providing an accurate assessment of somatic mutations at the genomic scale...
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Method: The SeqSplice multiplexed minigene splicing assay for characterization and quantitation of variant-induced BRCA1 and BRCA2 splice isoforms
- Daffodil M. Canson,
- Michael T. Parsons,
- Gemma Moir-Meyer,
- Troy Dumenil,
- Gemma Montalban,
- Erica Lin,
- Terri P. McVeigh,
- Aimee L. Davidson,
- Shaun M. Bouckaert,
- Matt Trau,
- Darren Korbie,
- and Amanda B. Spurdle
Genome Res. September 2025 35: 2104-2115; Published in Advance August 6, 2025, doi:10.1101/gr.279557.124
...alternative splicing across multiple exons, and are high priority for review in the context of variant pathogenicity assessment.DiscussionWe present SeqSplice, a high-throughput minigene splicing assay using a barcode approach that enabled simultaneous quantitative characterization of 1269 samples...
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Method: Surveying mutation density patterns around specific genomic features
- Hui Yu,
- Scott Ness,
- Chung-I Li,
- Yongsheng Bai,
- Peng Mao,
- and Yan Guo
Genome Res. October 2022 32: 1930-1940; Published in Advance September 13, 2022, doi:10.1101/gr.276770.122
...and model species. By scanning the bidirectional vicinity regions of given positions, MutDens systematically characterizes the mutation density for single-base substitution mutational classes after adjusting for total mutation burden and local nucleotide proportion. Analysis results using MutDens not only...

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