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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
.... 2007; Turpin et al. 2016). Thus, a deeper understanding of these resistance mechanisms remains a critical challenge in overcoming and managing breast cancer tumors expressing HER2.Alternative splicing, a fundamental post-transcriptional process in eukaryotic gene expression, allows a single gene locus...
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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
...in neurons is well established, yet few studies have examined activity-dependent alternative splicing. Alternative splicing regulates >95% of genes and is essential to diverse neuronal functions, including synapse development and calcium channel diversity. Alternative splicing is regulated by the expression...
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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
...genes) (see Supplemental Table S1), those previously detected in mRNA/EST sequences, and those identified in RNA-seq data (Yan et al. 2015). SSU was calculated for all 5′ or 3′ splice sites with a read coverage of 20 or more and estimated standard deviation ≤0.1, whereas sites with an insufficient...
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Resource: Multitissue single-nucleus RNA-seq reveals cell type–specific regulatory patterns of alternative polyadenylation in pigs
- Qiuhan Wen,
- Zhen Wang,
- Qi Bao,
- Tianli Ding,
- Haihan Zhang,
- Jianbo Li,
- Zhuang Liu,
- Jieping Huang,
- and Guoqiang Yi
Genome Res. September 2025 35: 2116-2129; Published in Advance June 16, 2025, doi:10.1101/gr.280095.124
...′ UTR of the CD47 gene, significantly impacts gene splicing and is strongly associated with reproductive phenotypes. Additionally, we observe that neuronal cells generally possess longer 3′ UTRs—a pattern conserved across humans, mice, fruit flies, and pigs. Together, these findings enrich the single...
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Method: Assessing conservation of alternative splicing with evolutionary splicing graphs
- Diego Javier Zea,
- Sofya Laskina,
- Alexis Baudin,
- Hugues Richard,
- and Elodie Laine
Genome Res. August 2021 31: 1462-1473; Published in Advance June 15, 2021, doi:10.1101/gr.274696.120
...across species. We show a clear link between the functional relevance, tissue regulation, and conservation of alternative transcripts on a set of 50 genes. By scaling up to the whole human protein-coding , we identify a few thousand genes where alternative splicing modulates the number and composition...
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Method: Modeling gene interactions in polygenic prediction via geometric deep learning
- Han Li,
- Jianyang Zeng,
- Michael P. Snyder,
- and Sai Zhang
Genome Res. January 2025 35: 178-187; Published in Advance November 19, 2024, doi:10.1101/gr.279694.124
..., to calculate gene-level PRSs in our implementation, but we recognize the possibilities of using alternative approaches, such as PRSice2, or even combinations of these approaches for gene-level PRS computation.One of the key motivations of our work is to empower biological discovery via model interpretation...
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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
...the PDB helps predict putative rare driver events in lung tumors. By extending the analysis with high-quality structural models from AlphaFold using The Encyclopedia of Domains (TED), we find a significant increase in the diversity of both genes and functional families with postduplication FIEs in lung...
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Research: SWATH-MS-based proteogenomic analysis reveals the involvement of alternative splicing in poplar upon lead stress
- Fu-Yuan Zhu,
- Xin Chen,
- Yu-Chen Song,
- Lydia Pui Ying Lam,
- Yuki Tobimatsu,
- Bei Gao,
- Mo-Xian Chen,
- and Fu-Liang Cao
Genome Res. March 2023 33: 371-385; Published in Advance March 24, 2023, doi:10.1101/gr.277473.122
...Laboratory of Ecological Security and Sustainable Development in Arid Areas, Urumqi, Xinjiang 830054, China ↵6 These authors contributed equally to this work. Corresponding authors: cmx2009920734@gmail.com, fuliangcaonjfu@163.comAbstractAlternative splicing (AS) regulates gene expression and increases...
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Method: Parallel analysis of replication timing, gene expression, and copy number with PARTAGE
- Lakshana Sruthi Sadu Murari,
- Quinn Dickinson,
- Silvia Meyer-Nava,
- and Juan Carlos Rivera-Mulia
Genome Res. March 19, 2026 ; Published in Advance March 19, 2026, doi:10.1101/gr.281532.125
...a more accurate integrated view of the complex relationships between RT and gene regulation. [Supplemental material is available for this article.] Human cells duplicate their by the firing of thousands of origins that are activated in clusters following a precise temporal order (Rivera-Mulia and Gilbert...
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Method: The SeqSplice multiplexed minigene splicing assay for characterization and quantitation of variant-induced BRCA1 and BRCA2 splice isoforms
- Daffodil M. Canson,
- Michael T. Parsons,
- Gemma Moir-Meyer,
- Troy Dumenil,
- Gemma Montalban,
- Erica Lin,
- Terri P. McVeigh,
- Aimee L. Davidson,
- Shaun M. Bouckaert,
- Matt Trau,
- Darren Korbie,
- and Amanda B. Spurdle
Genome Res. September 2025 35: 2104-2115; Published in Advance August 6, 2025, doi:10.1101/gr.279557.124
...from 21 publications with splicing assay results derived from a range of materials (including patient RNA, minigenes with single-exon or multiexon inserts, and experimental models containing the entire BRCA1 or BRCA2 gene) and varying assay methodologies (Supplemental Table S3).Only eight of 42...

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