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Method: Seamless, rapid, and accurate analyses of outbreak genomic data using split k-mer analysis
- Romain Derelle,
- Johanna von Wachsmann,
- Tommi Mäklin,
- Joel Hellewell,
- Timothy Russell,
- Ajit Lalvani,
- Leonid Chindelevitch,
- Nicholas J. Croucher,
- Simon R. Harris,
- and John A. Lees
Genome Res. October 2024 34: 1661-1673; Published in Advance October 15, 2024, doi:10.1101/gr.279449.124
...split k-mers for each substitution in the simulation and calculated power as the proportion of these detected by running ska align between the starting sequence and the mutated sequence. We calculated power requiring an exact match of the split k-mer and the correct middle base, as well as also a more...
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Research: The aberrant epigenome of DNMT3B-mutated ICF1 patient iPSCs is amenable to correction, with the exception of a subset of regions with H3K4me3- and/or CTCF-based epigenetic memory
- Varsha Poondi Krishnan,
- Barbara Morone,
- Shir Toubiana,
- Monika Krzak,
- Salvatore Fioriniello,
- Floriana Della Ragione,
- Maria Strazzullo,
- Claudia Angelini,
- Sara Selig,
- and Maria R. Matarazzo
Genome Res. February 2023 33: 169-183; Published in Advance February 24, 2023, doi:10.1101/gr.276986.122
...and the dynamics of epigenetics abnormalities in the context of early development.By performing homology directed repair (HDR) based gene-editing with CRISPR-Cas9 technology we recently corrected DNMT3B mutations in ICF1 iPSC lines derived from two patients (Toubiana et al. 2019). Focusing on repetitive regions...
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Method: A versatile type VI CRISPR-based approach for targeted m⁶A demethylation in mRNAs
- Panagiotis G. Adamopoulos,
- Konstantina Athanasopoulou,
- and Andreas Scorilas
Genome Res. January 2026 36: 169-182; Published in Advance December 11, 2025, doi:10.1101/gr.280476.125
...information on a target site of interest.The advent of innovative methodologies, such as those integrating CRISPR/Cas systems with RNA-processing approaches, has expedited research in this domain, furnishing novel tools for dissecting the roles of post-transcriptional modifications in gene expression dynamics...
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Method: Structure-optimized sgRNA selection with PlatinumCRISPr for efficient Cas9 generation of knockouts
- Irmgard U. Haussmann,
- Thomas C. Dix,
- David W.J. McQuarrie,
- Veronica Dezi,
- Abdullah I. Hans,
- Roland Arnold,
- and Matthias Soller
Genome Res. December 2024 34: 2279-2292; Published in Advance December 3, 2024, doi:10.1101/gr.279479.124
...RNA design including correct sgRNA folding (https://platinum-crispr.bham.ac.uk/predict.pl). Moreover, we provide guidelines to generate complete gene knockouts by generating deletions using dual sgRNAs. Taken together, these new sgRNA design and gene editing tools will help to develop CRISPR–Cas9 editing...
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Research: Characterization of the role of spatial proximity of DNA double-strand breaks in the formation of CRISPR-Cas9-induced large structural variations
- Mikkel Dahl-Jessen,
- Thorkild Terkelsen,
- Rasmus O. Bak,
- and Uffe Birk Jensen
Genome Res. February 2025 35: 231-241; Published in Advance January 13, 2025, doi:10.1101/gr.278575.123
...is a significant predictor of large-scale deletion and inversion frequency induced by CRISPR-Cas9 in K562 cells. This finding has implications for understanding SVs in the human and for the future application of CRISPR-Cas9 in gene editing and the modeling of rare SVs.Structural variations (SVs) encompass...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...in incomplete knockdown and can suffer from off-target effects, which complicate interpretation of transcriptional changes.Genome editing approaches, such as CRISPR–Cas9-mediated knockout (Nakamura et al. 2021), enable permanent removal of a TF. Knockouts are powerful for defining essential regulatory roles...
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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
...a seemingly divergent mechanism of myosin regulation across species, as C3 is important for human cardiac myosin expression in adulthood (Gacita et al. 2021).CRISPR-mediated epigenetic editing of R3 modulates cellular response to disease-related stimuliWe next sought to link the activity of this region...
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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
...include ReDACT, in which CRISPR is used to introduce a positive–negative selection cassette onto an aneuploid chromosome, and a kinesin-based approach in which a plant kinesin is used to drag a chromosome to the wrong centrosome (Girish et al. 2023; Tovini et al. 2023; Truong et al. 2023). We elected...
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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
...functional diversification during evolution. In this study, we seek to identify the diversification and potential gene neofunctionalization of lung tumors in the TRACERx cohort. We develop a novel computational protocol to identify preduplication and postduplication mutations predicted to affect protein...
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Research: Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations
- Irene Mei,
- Susanne Nichterwitz,
- Melanie Leboeuf,
- Jik Nijssen,
- Isadora Lenoel,
- Dirk Repsilber,
- Christian S. Lobsiger,
- and Eva Hedlund
Genome Res. September 2025 35: 1975-1991; Published in Advance July 17, 2025, doi:10.1101/gr.279501.124
...-cell RNA-seq data set, Namboori et al. (2021), on induced pluripotent stem cell (iPSC)–derived neurons harboring a SOD1E100G mutation (or corrected control iPSCs), at a time when the MNs were starting to degenerate in culture (Fig. 6A). From these RNA-seq data, we selected MNs (N = 115) only, based...
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