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Research: Deciphering the largest disease-associated transcript isoforms in the human neural retina with advanced long-read sequencing approaches
- Merel Stemerdink,
- Tabea Riepe,
- Nick Zomer,
- Renee Salz,
- Michael Kwint,
- Jaap Oostrik,
- Raoul Timmermans,
- Barbara Ferrari,
- Stefano Ferrari,
- Alfredo Dueñas Rey,
- Emma Delanote,
- Suzanne E. de Bruijn,
- Hannie Kremer,
- Susanne Roosing,
- Frauke Coppieters,
- Alexander Hoischen,
- Frans P.M. Cremers,
- Peter A.C. ‘t Hoen,
- Erwin van Wijk,
- and Erik de Vrieze
Genome Res. April 2025 35: 725-739; Published in Advance March 4, 2025, doi:10.1101/gr.280060.124
...used for genomic DNA capture. This method facilitated the successful capture and sequencing of ADGRV1 transcripts as well as full-length 18.9 kb USH2A transcripts. By combining algorithmic analysis with detailed manual curation of sequenced reads, we identified novel isoforms characterized...
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Method: Long-read subcellular fractionation and sequencing reveals the translational fate of full-length mRNA isoforms during neuronal differentiation
- Alexander J. Ritter,
- Jolene M. Draper,
- Christopher Vollmers,
- and Jeremy R. Sanford
Genome Res. November 2024 34: 2000-2011; Published in Advance June 5, 2024, doi:10.1101/gr.279170.124
...of the translated transcriptome.ResultsCharacterization of a transcriptome supplemented with long-read-derived novel transcriptsTo investigate the relationship between alternative pre-mRNA splicing and isoform-specific mRNA translation, we capitalized on the capability of long-read sequencing to capture complete...
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Method: Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences
- Chencheng Xu,
- Suying Bao,
- Ye Wang,
- Wenxing Li,
- Hao Chen,
- Yufeng Shen,
- Tao Jiang,
- and Chaolin Zhang
Genome Res. July 2024 34: 1052-1065; Published in Advance July 26, 2024, doi:10.1101/gr.279044.124
.... However, the current methods for the quantitative prediction of splice site usage still have limited accuracy. Here, we present DeltaSplice, a deep neural network model optimized to learn the impact of mutations on quantitative changes in alternative splicing from the comparative analysis of homologous...
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Research: Meta-analysis of activated neurons reveals dynamic regulation of diverse classes of alternative splicing
- Keegan S. Krick,
- Marissa Maroni,
- Erica Korb,
- Kristen W. Lynch,
- and Elizabeth A. Heller
Genome Res. June 2025 35: 1301-1312; Published in Advance April 24, 2025, doi:10.1101/gr.280082.124
...whose inclusion increased. We treated primary mouse cortical neuronal cultures with 55 mM KCl for 2 h to reflect “moderate” treatment. We assayed splicing using 32P-radiolabeled RT-PCR (Fig. 2E) and validated the predicted changes in PSI, in both direction and magnitude, for four of the candidate exons...
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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
...comprehensively characterize the HER2 alternative splicing isoforms, assess their expression in primary BC patients and cell lines, and explore their role in resistance to anti-HER2 therapies. We expand the catalog of known HER2 protein-coding isoforms from 13 to 90, revealing distinct patterns of protein domains...
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Resource: Native RNA sequencing in fission yeast reveals frequent alternative splicing isoforms
- José Carlos Montañés,
- Marta Huertas,
- Simone G. Moro,
- William R. Blevins,
- Mercè Carmona,
- José Ayté,
- Elena Hidalgo,
- and M. Mar Albà
Genome Res. June 2022 32: 1215-1227; Published in Advance May 26, 2022, doi:10.1101/gr.276516.121
.../intron inclusion and exclusion events, as well as by the use of alternative splice sites. The capacity of this gene to generate many alternative isoforms might be important for the ongoing arms race that characterizes the gene family.To quantify the isoform expression levels, we mapped the dRNA reads...
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Research: Comprehensive isoform-level analysis reveals the contribution of alternative isoforms to venom evolution and repertoire diversity
- Xinhai Ye,
- Chun He,
- Yi Yang,
- Yu H. Sun,
- Shijiao Xiong,
- Kevin C. Chan,
- Yuxuan Si,
- Shan Xiao,
- Xianxin Zhao,
- Haiwei Lin,
- Yang Mei,
- Yufeng Yao,
- Gongyin Ye,
- Fei Wu,
- and Qi Fang
Genome Res. September 2023 33: 1554-1567; Published in Advance October 5, 2023, doi:10.1101/gr.277707.123
...will be necessary.Comprehensive identification of venom genes in P. puparumBased on our updated annotation, we used a comprehensive approach combining transcriptomic (transcription-level) and proteomic (translation-level) evidence to systematically characterize venom genes and identify splicing isoforms...
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Resource: MPRAbase a Massively Parallel Reporter Assay database
- Jingjing Zhao,
- Fotis A Baltoumas,
- Maxwell A Konnaris,
- Ioannis Mouratidis,
- Zhe Liu,
- Jasmine Sims,
- Vikram Agarwal,
- Georgios A Pavlopoulos,
- Ilias Georgakopoulos-Soares,
- and Nadav Ahituv
Genome Res. April 22, 2025 gr.280387.124; Published in Advance April 22, 2025, doi:10.1101/gr.280387.124
...-regulatory elements with putative roles in transcriptional gene regulation have been identified (Encode Project Consortium 2012; Thurman et al. 2012). Following up on their annotation, a major challenge has been to functionally characterize these elements. Massively parallel reporter assays (MPRAs) were built...
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Research: Characterization of DNA methylation reader proteins in Arabidopsis thaliana
- Jonathan Cahn,
- James P.B. Lloyd,
- Ino D. Karemaker,
- Pascal W.T.C. Jansen,
- Jahnvi Pflueger,
- Owen Duncan,
- Jakob Petereit,
- Ozren Bogdanovic,
- A. Harvey Millar,
- Michiel Vermeulen,
- and Ryan Lister
Genome Res. December 2024 34: 2229-2243; Published in Advance December 4, 2024, doi:10.1101/gr.279379.124
...-down assay combined with quantitative mass spectrometry using methylated DNA probes for each DNA sequence context. All mC readers known to date preferentially bind to the methylated probes, along with a range of new mC-binding protein candidates. Functional characterization of these mC readers, focused...
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Research: Systematic identification and characterization of exon–intron circRNAs
- Yinchun Zhong,
- Yan Yang,
- Xiaolin Wang,
- Bingbing Ren,
- Xueren Wang,
- Ge Shan,
- and Liang Chen
Genome Res. March 2024 34: 376-393; Published in Advance April 12, 2024, doi:10.1101/gr.278590.123
...Systematic identification and characterization of exon–intron circRNAs Yinchun Zhong1,6, Yan Yang2,6, Xiaolin Wang2, Bingbing Ren3, Xueren Wang4,5, Ge Shan2 and Liang Chen1 1Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science...
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