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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
...dimension of this challenge. This study aims to comprehensively characterize the landscape of HER2 alternative splicing isoforms in breast cancer and to investigate their potential role in mediating resistance to anti-HER2 therapies, particularly ADCs. By employing long-read sequencing technology...
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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
...of alternative splicing patterns and histone post-translational modifications (hPTMs) across mouse brain development finds that enrichment of chromatin modifications correlates with, and predicts, alternative exon inclusion (Hu et al. 2017, 2020; Xu et al. 2017, 2018). Alternative splicing of neurexin I (Nrxn1...
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Method: Automated interpretable artificial intelligence genomic prediction with AIGP
- Lei Wei,
- Ziqin Jiang,
- Baoliang Fan,
- Yidan Yan,
- Zhenqiang Xu,
- Xiaoxiang Hu,
- and Yuzhe Wang
Genome Res. March 5, 2026 gr.281006.125; Published in Advance March 5, 2026, doi:10.1101/gr.281006.125
...-10-62733394. 14 Email: huxx@cau.edu.cn. 15 Yuzhe Wang, State Key Laboratory of Animal Biotech Breeding, College of Biological 16 Sciences, China Agricultural University, Beijing, 100193, China. Phone +86-10-62731314. 17 Email: yuzhe891@cau.edu.cn. 18 19 Abstract 20 Predicting phenotypes from genomic mutations...
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Method: Accurate detection of tandem repeats from error-prone sequences with EquiRep
- Zhezheng Song,
- Tasfia Zahin,
- Xiang Li,
- and Mingfu Shao
Genome Res. December 2025 35: 2714-2721; Published in Advance August 21, 2025, doi:10.1101/gr.280750.125
...the sequence of the underlying repeat unit. Although several methods exist, they often exhibit low accuracy when the repeat unit length increases or the number of copies is low. Furthermore, methods capable of handling highly mutated sequences remain scarce, highlighting a significant opportunity...
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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
...by integrating the SpliceAI alternate score for splice site gain (i.e., the final score of new or cryptic splice site after a variant has been incorporated into the reference sequence) to improve prediction of partial exon deletion and partial intron retention. This updated algorithm positively predicts variants...
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Method: A simple method for finding related sequences by adding probabilities of alternative alignments
- Martin C. Frith
Genome Res. August 2024 34: 1165-1173; Published in Advance August 16, 2024, doi:10.1101/gr.279464.124
...sequences. Unfortunately, it is hard to tell if an alignment is likely to exist by chance. Also, the precise alignment of related regions is uncertain. One alignment does not hold all evidence that they are related. We should consider alternative alignments too. This is rarely done, because we lack a simple...
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Method: Early feature extraction drives model performance in high-resolution chromatin accessibility prediction
- Aayush Grover,
- Till Muser,
- Liine Kasak,
- Lin Zhang,
- Ekaterina Krymova,
- and Valentina Boeva
Genome Res. March 2026 36: 619-629; Published in Advance January 12, 2026, doi:10.1101/gr.281042.125
...alternative for estimating changes in chromatin accessibility induced by the genetic variants in a cell type–specific manner.Numerous deep learning approaches have been proposed to predict chromatin accessibility from DNA sequence. Earlier methods (Zhou and Troyanskaya 2015; Kelley et al. 2016; Quang and Xie...
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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
...and predictors based on DEGs identified in our study and across multiple published data sets, which predict disease across SOD1 mutations and species.DiscussionWe conducted RNA sequencing analysis of MNs displaying differential vulnerability to degeneration in ALS to unveil mechanisms of protection...
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Method: Identification of the shortest species-specific oligonucleotide sequences
- Ioannis Mouratidis,
- Maxwell A. Konnaris,
- Nikol Chantzi,
- Candace S.Y. Chan,
- Michail Patsakis,
- Kimonas Provatas,
- Austin Montgomery,
- Fotis A. Baltoumas,
- Congzhou M. Sha,
- Manvita Mareboina,
- Georgios A. Pavlopoulos,
- Dionysios V. Chartoumpekis,
- and Ilias Georgakopoulos-Soares
Genome Res. February 2025 35: 279-295; Published in Advance January 2, 2025, doi:10.1101/gr.280070.124
...genomics and phylogeny analyses identified regions of organismal s that show patterns of accelerated evolution (Ferris et al. 2018; Foley et al. 2023). The usage of mutation rate patterns, species sequence alignments, and the identification of highly conserved regions can provide insights into phenotypic...
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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
...To comprehensively profile alternative polyadenylation across pig tissues, we analyzed 10x Genomics single-nucleus RNA sequencing (10x snRNA-seq) data from our previous study as a preprint on bioRxiv (Chen et al. 2023), which identified 261 cell subtypes spanning 19 distinct pig tissues (Supplemental Table S1...

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