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Method: Tissular chromatin-state cartography based on double-barcoded DNA arrays that capture unloaded PA-Tn5 transposase
- Maria Grazia Mendoza-Ferri,
- Gwendoline Lozachmeur,
- Maximilien Duvina,
- Laetitia Perret,
- Didier Merciris,
- Anne Gigout,
- and Marco Antonio Mendoza-Parra
Genome Res. July 2025 35: 1633-1645; Published in Advance May 13, 2025, doi:10.1101/gr.280305.124
...for capturing chromatin histone modification signatures across tissue sections by taking advantage of a double-barcoded DNA arrays design compatible with in situ Protein A–transposase Tn5 tagmentation. This approach has been validated in presence of fresh-frozen mouse brain tissues but also in decalcified...
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Method: Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling
- Li-Ting Chen,
- Myrthe Jager,
- Dàmi Rebergen,
- Geertruid J. Brink,
- Tom van den Ende,
- Willem Vanderlinden,
- Pauline Kolbeck,
- Marc Pagès-Gallego,
- Ymke van der Pol,
- Nicolle Besselink,
- Norbert Moldovan,
- Nizar Hami,
- Wigard P. Kloosterman,
- Hanneke van Laarhoven,
- Florent Mouliere,
- Ronald Zweemer,
- Jan Lipfert,
- Sarah Derks,
- Alessio Marcozzi,
- and Jeroen de Ridder
Genome Res. April 2025 35: 886-899; Published in Advance January 13, 2025, doi:10.1101/gr.279144.124
...BX, United Kingdom Corresponding authors: alessio.marcozzi@gmail.com, j.deridder-4@umcutrecht.nlAbstractShallow -wide cell-free DNA sequencing holds great promise for noninvasive cancer monitoring by providing reliable copy number alteration (CNA) and fragmentomic profiles. Single...
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Research: Purifying selection on noncoding deletions of human regulatory loci detected using their cellular pleiotropy
- David W. Radke,
- Jae Hoon Sul,
- Daniel J. Balick,
- Sebastian Akle,
- Alzheimer's Disease Neuroimaging Initiative,
- Robert C. Green,
- and Shamil R. Sunyaev
Genome Res. June 2021 31: 935-946; Published in Advance May 7, 2021, doi:10.1101/gr.275263.121
...(what we term “cellular pleiotropy”; i.e., the same regulatory locus is active in more than one biosample) might be expected to be, on average, more deleterious (i.e., fitness-reducing) than deletions that remove sites with activity specific to a particular biosample, because any changes at the DNA...
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Method: Enhancing CRISPR deletion via pharmacological delay of DNA-PKcs
- Núria Bosch-Guiteras,
- Tina Uroda,
- Hugo A. Guillen-Ramirez,
- Rahel Riedo,
- Amiq Gazdhar,
- Roberta Esposito,
- Carlos Pulido-Quetglas,
- Yitzhak Zimmer,
- Michaela Medová,
- and Rory Johnson
Genome Res. March 2021 31: 461-471; Published in Advance February 11, 2021, doi:10.1101/gr.265736.120
...genes.We sought to test the benefit of iDNA-PKcs in a realistic fitness screen in cancer cells (Fig. 4B; Zhu et al. 2016; Esposito et al. 2019). To do so, we created a library of pgRNAs targeting positive-control essential genes (348 pgRNAs, 59 target genes) and neutral-control intergenic regions (632...
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Research: Cis-acting variation is common across regulatory layers but is often buffered during embryonic development
- Swann Floc'hlay,
- Emily S. Wong,
- Bingqing Zhao,
- Rebecca R. Viales,
- Morgane Thomas-Chollier,
- Denis Thieffry,
- David A. Garfield,
- and Eileen E.M. Furlong
Genome Res. February 2021 31: 211-224; Published in Advance December 11, 2020, doi:10.1101/gr.266338.120
...mutations can have large effects, many behave effectively neutrally, making predictions of the functional impact of genetic variants extremely challenging. Part of the difficulty comes from a general lack of knowledge about which regions of noncoding DNA have regulatory (not just biochemical) function...
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Research: Comprehensive identification and analysis of human accelerated regulatory DNA
- Rachel M. Gittelman,
- Enna Hun,
- Ferhat Ay,
- Jennifer Madeoy,
- Len Pennacchio,
- William S. Noble,
- R. David Hawkins,
- and Joshua M. Akey
Genome Res. September 2015 25: 1245-1255; Published in Advance June 23, 2015, doi:10.1101/gr.192591.115
...regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. Footnotes...
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Research: Widespread cis-regulatory convergence between the extinct Tasmanian tiger and gray wolf
- Charles Y. Feigin,
- Axel H. Newton,
- and Andrew J. Pask
Genome Res. October 2019 29: 1648-1658; Published in Advance September 18, 2019, doi:10.1101/gr.244251.118
...craniofacial morphologies, and evidence suggests that they filled similar ecological niches. Previous analyses revealed little evidence of adaptive convergence between their protein-coding genes. Thus, the genetic basis of their convergence is still unclear. Here, we identified candidate craniofacial cis-regulatory...
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Research: CG dinucleotides enhance promoter activity independent of DNA methylation
- Dominik Hartl,
- Arnaud R. Krebs,
- Ralph S. Grand,
- Tuncay Baubec,
- Luke Isbel,
- Christiane Wirbelauer,
- Lukas Burger,
- and Dirk Schübeler
Genome Res. April 2019 29: 554-563; Published in Advance February 1, 2019, doi:10.1101/gr.241653.118
...sequences in parallel and in the context of chromosomal DNA. This requires a sequencing strategy that links RNA molecules (i.e., expression counts) to upstream regulatory regions that are not part of the transcript. Toward this goal, we designed a parallel reporter assay called TrAC-seq (Transcriptional...
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Resource: A comparison of gene expression and DNA methylation patterns across tissues and species
- Lauren E. Blake,
- Julien Roux,
- Irene Hernando-Herraez,
- Nicholas E. Banovich,
- Raquel Garcia Perez,
- Chiaowen Joyce Hsiao,
- Ittai Eres,
- Claudia Cuevas,
- Tomas Marques-Bonet,
- and Yoav Gilad
Genome Res. February 2020 30: 250-262; Published in Advance January 17, 2020, doi:10.1101/gr.254904.119
...-primate differences in regulatory mechanisms and phenotypes other than gene expression levels, such as DNA methylation levels, chromatin modifications and accessibility, and protein expression levels (Cain et al. 2011; Pai et al. 2011; Hernando-Herraez et al. 2013, 2015a,b; Ward et al. 2013; Stergachis et al. 2014...
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Research: Impact of the X Chromosome and sex on regulatory variation
- Kimberly R. Kukurba,
- Princy Parsana,
- Brunilda Balliu,
- Kevin S. Smith,
- Zachary Zappala,
- David A. Knowles,
- Marie-Julie Favé,
- Joe R. Davis,
- Xin Li,
- Xiaowei Zhu,
- James B. Potash,
- Myrna M. Weissman,
- Jianxin Shi,
- Anshul Kundaje,
- Douglas F. Levinson,
- Philip Awadalla,
- Sara Mostafavi,
- Alexis Battle,
- and Stephen B. Montgomery
Genome Res. June 2016 26: 768-777; Published in Advance April 21, 2016, doi:10.1101/gr.197897.115
...on nonstatistical grounds. Further, our study identifies differences in purifying selection for eQTL on the X Chromosome versus the autosomes; however, as many common variants are likely neutral, future studies will benefit from considering low frequency and rare regulatory variants, as it is increasingly evident...
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