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Method: 3′-end ligation sequencing is a sensitive method to detect DNA nicks at potential sites of off-target activity induced by prime editors
- Jacob Stewart-Ornstein,
- Matthew J. Irby,
- Marina K. Lilieholm,
- Dylan Laprise,
- Maria D. Collier,
- Thomas Aunins,
- Dewi Harjanto,
- Aaron N. Chang,
- Deepak Reyon,
- and Jeremy S. Duffield
Genome Res. September 2025 35: 2064-2075; Published in Advance August 5, 2025, doi:10.1101/gr.280164.124
..., in vitro approaches, in which the editor is combined with human genomic DNA and sites where editing may occur are identified biochemically, are important tools. Existing biochemical approaches for off-target discovery recognize double-stranded breaks generated by nuclease-based gene editors such as SpCas9...
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Research: Lambdoid phages with abundant Chi recombination hotspots reflect diverse viral strategies for recombination-dependent growth
- Clarence Zheng,
- Sherwood R. Casjens,
- Alan R. Davidson,
- Susan K. Amundsen,
- and Gerald R. Smith
Genome Res. August 2025 35: 1767-1780; Published in Advance July 10, 2025, doi:10.1101/gr.280248.124
...the other three. We later noted previous reports of very closely related phages being isolated in even more distant global positions, such as Norway, Greece, and Chile or such as Puerto Rico and Antarctica, and sometimes across several years (Breitbart et al. 2004; Kalatzis et al. 2017; Bellas et al. 2020...
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Method: A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs
- Christian Pflueger,
- Dennis Tan,
- Tessa Swain,
- Trung Nguyen,
- Jahnvi Pflueger,
- Christian Nefzger,
- Jose M. Polo,
- Ethan Ford,
- and Ryan Lister
Genome Res. August 2018 28: 1193-1206; Published in Advance June 15, 2018, doi:10.1101/gr.233049.117
.... 2012; Maurano et al. 2015). However, these pharmacological inhibitors of DNMTs alter the DNA methylation landscape globally, induce broad transcriptional changes, and result in highly pleiotropic off-target effects. Therefore, these are not suitable to understand the nuanced impact of DNA methylation...
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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
...al. 2015). Genome-wide increases in DNA methylation levels, particularly at CHH sites, were detected in cultured samples during somatic embryogenesis in soybean (Ji et al. 2019). In sweet orange, the global CHH methylation levels were significantly decreased at the callus induction stage...
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Resource: Global compositional and functional states of the human gut microbiome in health and disease
- Sunjae Lee,
- Theo Portlock,
- Emmanuelle Le Chatelier,
- Fernando Garcia-Guevara,
- Frederick Clasen,
- Florian Plaza Oñate,
- Nicolas Pons,
- Neelu Begum,
- Azadeh Harzandi,
- Ceri Proffitt,
- Dorines Rosario,
- Stefania Vaga,
- Junseok Park,
- Kalle von Feilitzen,
- Fredric Johansson,
- Cheng Zhang,
- Lindsey A. Edwards,
- Vincent Lombard,
- Franck Gauthier,
- Claire J. Steves,
- David Gomez-Cabrero,
- Bernard Henrissat,
- Doheon Lee,
- Lars Engstrand,
- Debbie L. Shawcross,
- Gordon Proctor,
- Mathieu Almeida,
- Jens Nielsen,
- Adil Mardinoglu,
- David L. Moyes,
- Stanislav Dusko Ehrlich,
- Mathias Uhlen,
- and Saeed Shoaie
Genome Res. June 2024 34: 967-978; Published in Advance July 22, 2024, doi:10.1101/gr.278637.123
...://www.microbiomeatlas.org).View larger version: In this window In a new window Figure 1. Characterization of the global gut microbiome in health and disease. Pan-metagenomics association studies of health and disease. Corresponding data sets were publicly shared as a resource: the Human Gut Microbiome Atlas (HGMA). (A) The geographical...
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Method: Highly accurate quantification of allelic gene expression for population and disease genetics
- Anna Saukkonen,
- Helena Kilpinen,
- and Alan Hodgkinson
Genome Res. August 2022 32: 1565-1572; Published in Advance July 6, 2022, doi:10.1101/gr.276296.121
....0/.References ↵The 1000 Genomes Project Consortium. 2015. A global reference for human genetic variation. Nature 526: 68–74. doi:10.1038/nature15393 ↵Castel SE, Levy-Moonshine A, Mohammadi P, Banks E, Lappalainen T. 2015. Tools and best practices for data processing in allelic expression analysis. Genome Biol...
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Method: Accurate transcriptome-wide identification and quantification of alternative polyadenylation from RNA-seq data with APAIQ
- Yongkang Long,
- Bin Zhang,
- Shuye Tian,
- Jia Jia Chan,
- Juexiao Zhou,
- Zhongxiao Li,
- Yisheng Li,
- Zheng An,
- Xingyu Liao,
- Yu Wang,
- Shiwei Sun,
- Ying Xu,
- Yvonne Tay,
- Wei Chen,
- and Xin Gao
Genome Res. April 2023 33: 644-657; Published in Advance April 28, 2023, doi:10.1101/gr.277177.122
...-seq data from TCGA, the landscape of APA regulating 3′ UTR lengthening and shortening has been characterized by several previous studies (Xia et al. 2014; Feng et al. 2018). On the other hand, global studies of APA using RNA-seq data from other regions, such as intronic regions, that could alter coding...
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Research: Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay
- Bertille Montibus,
- James A. Cain,
- Rocio T. Martinez-Nunez,
- and Rebecca J. Oakey
Genome Res. December 2024 34: 2163-2175; Published in Advance November 22, 2024, doi:10.1101/gr.279430.124
...gene expression. It showed that host genes had a greater variance in expression level (Supplemental Fig. S5A), suggesting that these genes are expressed in a limited set of tissues. As the standard deviation is influenced by the level of expression, we investigated the global level of expression across...
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Method: Identification and dynamic quantification of regulatory elements using total RNA
- Sascha H. Duttke,
- Max W. Chang,
- Sven Heinz,
- and Christopher Benner
Genome Res. November 2019 29: 1836-1846; Published in Advance October 24, 2019, doi:10.1101/gr.253492.119
...) and identified 54,000 candidate TSS clusters. Comparing these csRNA-defined TSS clusters with existing annotations and other data generated in K562 cells revealed a global overlap with known features of transcription initiation (Supplemental Fig. S3A). Ninety-four percent of the TSSs mapped to promoter...
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Research: Global loss of cellular m⁶A RNA methylation following infection with different SARS-CoV-2 variants
- Roshan Vaid,
- Akram Mendez,
- Ketan Thombare,
- Rebeca Burgos-Panadero,
- Rémy Robinot,
- Barbara F. Fonseca,
- Nikhil R. Gandasi,
- Johan Ringlander,
- Mohammad Hassan Baig,
- Jae-June Dong,
- Jae Yong Cho,
- Björn Reinius,
- Lisa A. Chakrabarti,
- Kristina Nystrom,
- and Tanmoy Mondal
Genome Res. March 2023 33: 299-313; Published in Advance March 1, 2023, doi:10.1101/gr.276407.121
...antibody. Scale bar is 20 μm. (J) Quantification of METTL3–METTL14 PLA foci as detected in I. The number of PLA foci/nuclei are shown as mean ± SD. Data presented from multiple experiments with the total number of cells counted, n = <100. One-way ANOVA test was performed; (****) P < 0.0001.The global loss...
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