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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
..., revealing distinct mechanisms of potential resistance to anti-HER2 therapies, particularly ADCs. This expanded landscape of HER2 isoforms emphasizes the crucial role of alternative splicing investigations in advancing precision-targeted cancer therapies.Breast cancer remains one of the most prevalent...
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Method: Scalable cell-specific coexpression networks for granular regulatory pattern discovery with NeighbourNet
- Yidi Deng,
- Jiadong Mao,
- Jarny Choi,
- and Kim-Anh Lê Cao
Genome Res. April 2026 36: 785-801; Published in Advance March 5, 2026, doi:10.1101/gr.281171.125
...only limited downstream analyses of inferred networks, hindering their practical application and reducing their impact on biological discovery (Pratapa et al. 2020; Nguyen et al. 2021).To address these challenges, we present NeighbourNet (NNet), a novel method that uses k-nearest neighbor (KNN...
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Method: Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity
- Mayank Murali,
- Jamie Saquing,
- Senbao Lu,
- Ziyang Gao,
- Emily F. Watts,
- Ben Jordan,
- Zachary Peters Wakefield,
- Ana Fiszbein,
- David R. Cooper,
- Peter J. Castaldi,
- Dmitry Korkin,
- and Gloria M. Sheynkman
Genome Res. April 2025 35: 1012-1024; Published in Advance March 14, 2025, doi:10.1101/gr.279317.124
..., it is critical to track precise differences in protein isoform sequences and link such variations to the upstream explanatory mechanisms. However, it is challenging to systematically characterize the full interplay between genomic and proteomic variations, which hinders discoveries of novel biological variations...
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Research: Dynamics and consequences of differential RNA isoform production during cardiomyocyte fate determination and early-stage maturation
- Joanna Delimata-Raczek,
- Natalia Koralewska,
- Bart Krist,
- Magdalena Rakoczy,
- Marek Figlerowicz,
- and Ireneusz Stolarek
Genome Res. April 3, 2026 ; Published in Advance April 3, 2026, doi:10.1101/gr.281150.125
...precise control of cardiac-specific processes without altering overall gene expression. These results redefine transcriptional regulation during differentiation: Isoform switching is not merely a secondary layer of control but a central mechanism for establishing cell identity. By decoupling transcript...
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Resource: Isoform- and pathway-specific regulation of post-transcriptional RNA processing in human cells
- Ishwarya Venkata Narayanan,
- Karan Bedi,
- Brian Magnuson,
- Ariel McShane,
- Mario Ashaka,
- Michelle Paulsen,
- Thomas E Wilson,
- and Mats Ljungman
Genome Res. March 26, 2026 gr.280892.125; Published in Advance March 26, 2026, doi:10.1101/gr.280892.125
...Isoform and pathway-specific regulation of post-1 transcriptional RNA processing in human cells 2 3 Ishwarya Venkata Narayanan1,7, Karan Bedi1,2,3,7, Brian Magnuson1,4, Ariel McShane1.5, 4 Mario Ashaka1, Michelle T. Paulsen1, Thomas E. Wilson3,4 and Mats Ljungman1,3,6 5 6 1 Department of Radiation...
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Method: Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes
- Hongke Peng,
- Jafar S. Jabbari,
- Luyi Tian,
- Changqing Wang,
- Yupei You,
- Chong Chyn Chua,
- Natasha S. Anstee,
- Noorul Amin,
- Andrew H. Wei,
- Nadia M. Davidson,
- Andrew W. Roberts,
- David C.S. Huang,
- Matthew E. Ritchie,
- and Rachel Thijssen
Genome Res. April 2025 35: 942-955; Published in Advance January 10, 2025, doi:10.1101/gr.279322.124
.... Integration of unique barcode primers specific to ONT allowed pooling and efficient sequencing of multiple samples on the Nanopore platform. scRaCH-seq's capability to capture multiple transcripts simultaneously enhances isoform usage detection and facilitates the discovery of transcripts with mutations...
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Method: Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
- Qian Qin,
- Victoria Popic,
- Kirsty Wienand,
- Houlin Yu,
- Emily White,
- Akanksha Khorgade,
- Asa Shin,
- Christophe Georgescu,
- Catarina D. Campbell,
- Arthur Dondi,
- Niko Beerenwinkel,
- Francisca Vazquez,
- Aziz M. Al'Khafaji,
- and Brian J. Haas
Genome Res. April 2025 35: 967-986; Published in Advance March 14, 2025, doi:10.1101/gr.279200.124
...-highest accuracy. While LongGF was not found as a top-performing method in either of these PacBio MAS-ISO-seq fusion isoform benchmarking efforts, it notably has the highest precision of all methods with no FPs detected at a minimum two read evidence thresholds.Harnessing the strengths of long- and short...
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Method: Long-read Ribo-STAMP simultaneously measures transcription and translation with isoform resolution
- Pratibha Jagannatha,
- Alexandra T. Tankka,
- Daniel A. Lorenz,
- Tao Yu,
- Brian A. Yee,
- Kristopher W. Brannan,
- Cathy J. Zhou,
- Jason G. Underwood,
- and Gene W. Yeo
Genome Res. November 2024 34: 2012-2024; Published in Advance June 21, 2024, doi:10.1101/gr.279176.124
...-read sequencing, enabling the precise identification of all editable cytosines within individual RNA molecules and their associated isoforms. This is in contrast to short-read sequencing, which only provides a generalized view of editing events aggregated at the gene level, without the ability to differentiate...
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Review: Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics
- Natan Belchikov,
- Justine Hsu,
- Xiang Jennie Li,
- Julien Jarroux,
- Wen Hu,
- Anoushka Joglekar,
- and Hagen U. Tilgner
Genome Res. November 2024 34: 1735-1746; doi:10.1101/gr.279640.124
...). In a somewhat similar manner, ∼5000 unannotated, largely noncoding, genes were discovered in human embryos (Torre et al. 2023).A fundamental question regarding the discovery of novel isoforms is whether they should be included in state-of-the-art annotations, such as GENCODE (Harrow et al. 2012; Frankish et al...
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Method: A novel multislice framework for precision 3D spatial domain reconstruction and disease pathology analysis
- Daijun Zhang,
- Ren Qi,
- Xun Lan,
- and Bin Liu
Genome Res. August 2025 35: 1794-1808; Published in Advance July 14, 2025, doi:10.1101/gr.280281.124
...as a multislice joint analysis framework featuring a precorrection mechanism that enables the precise identification of complex spatial domains, advancing disease pathology insights. STMSC assumes that precise three-dimensional (3D) reconstruction is essential for an in-depth investigation of tissue components...

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