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Method: Highly efficient and scarless genome editing via essential gene-coupled homology-directed repair
- Joo Hye Yeo,
- Hyongbum Henry Kim,
- Sang Ho Oh,
- and Jinu Lee
Genome Res. April 15, 2026 gr.281194.125; Published in Advance April 15, 2026, doi:10.1101/gr.281194.125
...—a commonly used safe harbor site—and a donor plasmid 148 possessing a puromycin resistance gene for integration at this locus (Fig. 1C). 149 Puromycin selection was applied exclusively in the concurrent HDR condition to enrich 150 for cells in which HDR had occurred at AAVS1. HDR efficiency at the target...
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Method: Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution
- Paul Ashford,
- Alexander M. Frankell,
- Zofia Piszka,
- Camilla S.M. Pang,
- Mahnaz Abbasian,
- Maise Al Bakir,
- Mariam Jamal-Hanjani,
- Nicholas McGranahan,
- Charles Swanton,
- and Christine A. Orengo
Genome Res. March 2026 36: 561-577; Published in Advance February 19, 2026, doi:10.1101/gr.278663.123
..., known associations of GPI mutations with cancer, and implications based on the gene's multifunctional nature. From the analysis of R273's location in the substrate site, the probable loss of H-bonds coordinating catalytic site residues caused by a mutation from arginine to leucine (i.e., loss...
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Method: Robust and efficient annotation of cell states through gene signature scoring
- Laure Ciernik,
- Agnieszka Kraft,
- Florian Barkmann,
- Josephine Yates,
- and Valentina Boeva
Genome Res. March 2026 36: 630-644; Published in Advance February 18, 2026, doi:10.1101/gr.280926.125
...associated with patient survival and treatment resistance, accurate cell annotation is essential for identifying clinically relevant populations. Our analyses across nine healthy and cancer scRNA-seq data sets, covering diverse gene signatures and experimental conditions, revealed that established scoring...
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Resource: Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
- Kangli Wang,
- Weikun Xia,
- Yingli Gu,
- Songpeng Zu,
- Qian Yang,
- Maria Luisa Amaral,
- Yaozhi Wang,
- Allen Wang,
- Xiang-Dong Fu,
- William C. Mobley,
- and Bing Ren
Genome Res. April 2026 36: 849-864; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...–specific level, revealing a subset of genes that increasingly express with age and are enriched in PD-related pathways, notably in oligodendrocytes at late aging stages. Integration with five public PD single-cell RNA-seq data sets highlights 85 genes consistently differentially expressed with aging and PD. Key...
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Research: Ruminant-specific retrotransposons shape regulatory evolution of bovine immunity
- Conor J. Kelly,
- Carol G. Chitko-McKown,
- and Edward B. Chuong
Genome Res. August 2022 32: 1474-1486; Published in Advance August 10, 2022, doi:10.1101/gr.276241.121
...elements (TEs) are increasingly recognized to contribute to gene regulatory evolution and variation, but this possibility has been largely unexplored in ruminant s. We conducted epigenomic profiling of the type II interferon (IFN) response in bovine cells and found thousands of ruminant-specific TEs...
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Resource: An organism-wide ATAC-seq peak catalog for the bovine and its use to identify regulatory variants
- Can Yuan,
- Lijing Tang,
- Thomas Lopdell,
- Vyacheslav A. Petrov,
- Claire Oget-Ebrad,
- Gabriel Costa Monteiro Moreira,
- José Luis Gualdrón Duarte,
- Arnaud Sartelet,
- Zhangrui Cheng,
- Mazdak Salavati,
- D. Claire Wathes,
- Mark A. Crowe,
- GplusE Consortium,
- Wouter Coppieters,
- Mathew Littlejohn,
- Carole Charlier,
- Tom Druet,
- Michel Georges,
- and Haruko Takeda
Genome Res. October 2023 33: 1848-1864; Published in Advance September 26, 2023, doi:10.1101/gr.277947.123
...as well as the proportion of variants mapping to ATAC-seq peaks that are regulatory; and (5) a retrospective evaluation of the utility of this catalog for the identification of regulatory variants known in livestock species.ResultsGenerating a catalog of bovine cis-acting gene regulatory elements...
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Research: Natural diversity of telomere length distributions across 100 Saccharomyces cerevisiae strains
- Clotilde Garrido,
- Cintia Gómez-Muñoz,
- Etienne Kornobis,
- Nicolas Agier,
- Oana Ilioaia,
- Gilles Fischer,
- and Zhou Xu
Genome Res. March 2026 36: 522-533; Published in Advance January 16, 2026, doi:10.1101/gr.281132.125
...and Cooper 2010; Wellinger and Zakian 2012; de Lange 2018). These functions are tightly associated with the regulation of telomere length (TL). Indeed, telomeres are protected by proteins that prevent natural chromosome ends from being recognized as double-strand breaks, which would elicit a DNA damage...
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Method: Chromosome engineering to correct a complex rearrangement on Chromosome 8 reveals the effects of 8p syndrome on gene expression and neural differentiation
- Sophia N. Lee,
- Erin C. Banda,
- Lu Qiao,
- Sarah L. Thompson,
- Karan Singh,
- Ryan A. Hagenson,
- Teresa Davoli,
- Stefan F. Pinter,
- and Jason M. Sheltzer
Genome Res. March 2026 36: 547-560; Published in Advance January 12, 2026, doi:10.1101/gr.280425.125
...of Chromosome 8 and restore euploidy in cells derived from an individual with a complex rearrangement of Chromosome 8p. Transcriptomic analysis revealed 361 differentially expressed genes between the proband and the euploid revertant, highlighting genes both within and outside the 8p region that may contribute...
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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
...precisely capture subtle similarities and differences between cells in specific contexts, DeCEP incorporates an imputation step to refine the gene expression profiles. DeCEP can further convert the scores into DeCEP states by finding natural breaks in the data using the Fisher–Jenks algorithm (Fig. 1A...
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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
.... 2007; Turpin et al. 2016). Thus, a deeper understanding of these resistance mechanisms remains a critical challenge in overcoming and managing breast cancer tumors expressing HER2.Alternative splicing, a fundamental post-transcriptional process in eukaryotic gene expression, allows a single gene locus...

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