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Research: Long-read DNA and cDNA sequencing identify cancer-predisposing deep intronic variation in tumor-suppressor genes
- Suleyman Gulsuner,
- Amal AbuRayyan,
- Jessica B. Mandell,
- Ming K. Lee,
- Greta V. Bernier,
- Barbara M. Norquist,
- Sarah B. Pierce,
- Mary-Claire King,
- and Tom Walsh
Genome Res. November 2024 34: 1825-1831; Published in Advance September 13, 2024, doi:10.1101/gr.279158.124
...and cDNA sequencing, based on patient-derived DNA and RNA, to systematically evaluate deep intronic variation. We identified all variants across the full genomic loci of targeted genes, applied the in silico tools SpliceAI and Pangolin to predict variants of functional consequence, and then carried out...
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Research: Pangenome analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility
- Dongying Xie,
- Pohao Ye,
- Yiming Ma,
- and Zhongying Zhao
Genome Res. March 2026 36: 506-521; Published in Advance February 17, 2026, doi:10.1101/gr.280885.125
...and the translocation of one of its members, Cni-neib-1, to the center of Chr IV (Xie et al. 2024), we initially anticipated that the genomic region encompassing Cni-neib-1 would also exhibit rapid evolution. Unexpectedly, the ∼40 kb region surrounding Cni-neib-1 is invariant (>99% sequence identity) across both the cDNA...
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Mini-Review: A Hitchhiker's Guide to long-read genomic analysis
- Medhat Mahmoud,
- Daniel P. Agustinho,
- and Fritz J. Sedlazeck
Genome Res. April 2025 35: 545-558; doi:10.1101/gr.279975.124
..., expanding the applicability of long-read sequencing across diverse genomic studies (Wenger et al. 2019; Koren et al. 2024). Both platforms are capable of DNA and cDNA sequencing and detecting DNA methylation. At the same time, ONT offers additional functionalities such as adaptive sampling and direct RNA...
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Research: Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts
- Yanis Zekri,
- Sebastian Gregoricchio,
- Elif Yapıcı,
- Chia-Chi Flora Huang,
- Tunç Morova,
- Umut Berkay Altıntaş,
- Gozde Korkmaz,
- Nathan A. Lack,
- and Wilbert Zwart
Genome Res. July 2025 35: 1530-1543; Published in Advance June 10, 2025, doi:10.1101/gr.280320.124
...was extracted using TRIzol (Invitrogen), and poly(A) mRNA was isolated using the Oligo (dT)25 Dynabeads (Thermo Fisher Scientific) and reverse-transcribed into cDNA. The synthesized STARR-seq cDNA was amplified by a junction PCR, and Illumina-compatible libraries were sequenced on Illumina NovaSeq 6000 (150 bp...
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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
...by magnesium chloride, leading to the formation of hairpin-like DNA structures. (E) Scheme illustrating the molecular biology steps required for generating a copy of the genomic DNA captured by the DNA probes, followed by their amplification for Illumina massive parallel DNA sequencing.Printed DNA arrays...
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Research: Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations
- Yasine Malki,
- Guannan Kang,
- W.K. Jacky Lam,
- Qing Zhou,
- Suk Hang Cheng,
- Peter P.H. Cheung,
- Jinyue Bai,
- Ming Lok Chan,
- Chui Ting Lee,
- Wenlei Peng,
- Yiqiong Zhang,
- Wanxia Gai,
- Winsome W.S. Wong,
- Mary-Jane L. Ma,
- Wenshuo Li,
- Xinzhou Xu,
- Zhuoran Gao,
- Irene O.L. Tse,
- Huimin Shang,
- L.Y. Lois Choy,
- Peiyong Jiang,
- K.C. Allen Chan,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 31-42; Published in Advance November 27, 2024, doi:10.1101/gr.279667.124
...regions. Data from the target capture of all subjects (862 subjects) were retrieved for analysis. Only off-target DNA fragments were analyzed in this study to avoid the effects of target capture on fragmentomic analysis. Off-target reads were defined as DNA fragments with no full or partial alignment...
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Research: Continuous infiltration and evolutionary trajectory of nuclear organelle DNA in Oryza
- Chenbo Gong,
- Yicheng Huang,
- Mengmeng Liu,
- Yong Zhou,
- Yinwei Xu,
- Nahed Mohammed,
- Xintong Qiao,
- Andrea Zuccolo,
- Weibo Xie,
- Rod A. Wing,
- Jianwei Zhang,
- Fei Zhou,
- and Yongjun Lin
Genome Res. June 2025 35: 1349-1363; Published in Advance April 25, 2025, doi:10.1101/gr.279609.124
...one to four RNA-editing sites that had already changed to T bases, with no NIOGs showing C-to-T change at all RNA editing sites (Supplemental Table S6). These findings support that NORGs are transferred predominantly via DNA rather than via RNA or cDNA intermediates.Signatures of junction sites of de...
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Research: Assessing DNA methylation detection for primary human tissue using Nanopore sequencing
- Rylee Genner,
- Stuart Akeson,
- Melissa Meredith,
- Pilar Alvarez Jerez,
- Laksh Malik,
- Breeana Baker,
- Abigail Miano-Burkhardt,
- CARD-long-read Team,
- Benedict Paten,
- Kimberley J. Billingsley,
- Cornelis Blauwendraat,
- and Miten Jain
Genome Res. April 2025 35: 632-643; Published in Advance March 7, 2025, doi:10.1101/gr.279159.124
.... 1987; Li et al. 2018), genomic imprinting (Li et al. 1993; Suzuki et al. 2007; Court et al. 2014), X-Chromosome inactivation (Sharp et al. 2011), and transcription repression (Moore et al. 2013). As a result, variations in DNA methylation have been associated with human diseases such as aging...
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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
...). By looking at the mutations through -wide “breadth”, the limited number of equivalents becomes less restrictive, enabling the identification of tumor fractions (TFs) ∼100 times lower compared to targeted “depth” in SNV analysis (Zviran et al. 2020). Genome-wide cfDNA can also reveal tumor-specific copy...
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Research: Genomic insights into metabolic flux in hummingbirds
- Ariel Gershman,
- Quinn Hauck,
- Morag Dick,
- Jerrica M. Jamison,
- Michael Tassia,
- Xabier Agirrezabala,
- Saad Muhammad,
- Raafay Ali,
- Rachael E. Workman,
- Mikel Valle,
- G. William Wong,
- Kenneth C. Welch, Jr.,
- and Winston Timp
Genome Res. May 2023 33: 703-714; Published in Advance May 8, 2023, doi:10.1101/gr.276779.122
...-read sequencing were generated with the cDNA PCR sequencing kit (SQK-PCS109) from Oxford Nanopore Technologies according to the manufacturer's instructions. Libraries were each sequenced on a PromethION flow cell for 72 h.Genome annotation and transcriptome assemblyIllumina RNA-seq reads were trimmed...

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