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Research: Transcription and potential functions of a novel XIST isoform in male peripheral glia
- Kevin S. O'Leary,
- Meng-Yen Li,
- Kevyn Jackson,
- Lijie Shi,
- Elena Ezhkova,
- Bernice E. Morrow,
- and Deyou Zheng
Genome Res. February 2026 36: 257-274; Published in Advance December 12, 2025, doi:10.1101/gr.280832.125
...further performed transcriptomic profiling to characterize genes and pathways that may be affected by the expression of a new XIST isoform (termed “sXIST”) that we discovered in male peripheral glia. Using these systematic approaches, we aim to investigate (1) the cell/tissue type and disease relevance...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...sufficient. Combining tools with awareness of their limitations allows researchers to design experiments with high-confidence hypotheses. However, one of the major steps when trying to identify functional regions of a gene involves systematic perturbation of its regulatory DNA through deletion, linker...
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Method: A scalable computational framework for predicting gene expression from candidate cis-regulatory elements
- Qinhu Zhang,
- Siguo Wang,
- Zhipeng Li,
- Wenzheng Bao,
- Wenjian Liu,
- and De-Shuang Huang
Genome Res. February 2026 36: 361-374; Published in Advance January 16, 2026, doi:10.1101/gr.281219.125
..., and epigenomic tracks from discrete cCREs. A series of comparative experiments demonstrates the superiority and scalability of ScPGE. By comprehensively analyzing ScPGE's predictions, we identified distinct regulatory patterns in TPs, FPs, TNs, and FNs, particularly a pattern in TPs where the regulatory effect...
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Research: Genomic regulatory landscape underlying the antiviral response of Atlantic salmon
- Shahmir Naseer,
- Thomas C Clark,
- Bertrand Collet,
- Pooran Dewari,
- Damir Baranasic,
- Daniel J Macqueen,
- Pierre Boudinot,
- and Samuel A.M. Martin
Genome Res. October 22, 2025 gr.280579.125; Published in Advance October 22, 2025, doi:10.1101/gr.280579.125
...a signalling cascade leading to the 65 phosphorylation of the Janus kinases Tyk2 and JAK1, as well as the “signal transducers and 66 activators of transcription” STAT1 and STAT2 (Platanias, 2005). These phosphorylated 67 STAT1 and STAT2 molecules then bind with a third subunit, interferon regulatory factor 9...
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Research: Transcriptome-wide systematic search does not detect A-to-I RNA editing in cis-antisense RNA duplexes
- Zohar Rosenwasser,
- Roni Cohen-Fultheim,
- Ofir Shliefer,
- Erez Y. Levanon,
- and Eli Eisenberg
Genome Res. March 12, 2026 gr.280820.125; Published in Advance March 12, 2026, doi:10.1101/gr.280820.125
...) pathway, leading to the production of interferons and pro-inflammatory cytokines(Feng et al. 2012; Brisse and Ly 2019; Hur 2019). While this antiviral defense mechanism is essential for combating infections, inappropriate activation by self-derived dsRNA can result in unnecessary immune activation...
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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
..., and translation efficiency. In contrast, ALE-APA results from multiple PASs located in alternative terminal exons, which could lead to the production of truncated protein isoforms (Mariella et al. 2019; Goering et al. 2021). These alternatively polyadenylated mRNAs greatly expand the diversity of transcripts...
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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...between genetic variants and environmental stressors is key to understanding the mechanisms underlying neurological diseases. In this study, we use human brain organoids to explore how varying oxygen levels expose context-dependent gene regulatory effects. By subjecting a genetically diverse panel of 21...
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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
...conducted a detailed investigation of isoforms encoding p95-like proteins. Specifically, we analyzed the presence of upstream open reading frames (uORFs), known regulatory elements that modulate protein expression through various mechanisms (Young and Wek 2016). Among the p95 HER2 isoforms identified, six...
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Method: Deep structural clustering reveals hidden systematic biases in RNA sequencing data
- Qiang Su,
- Yi Long,
- Deming Gou,
- Junmin Quan,
- Xiaoming Zhou,
- and Qizhou Lian
Genome Res. November 2025 35: 2563-2577; Published in Advance September 19, 2025, doi:10.1101/gr.280713.125
...while meticulously preserving essential structural features crucial for bias identification. This sophisticated modeling allows precise tracking of local RNA-read conversion dynamics and the identification of complex, often overlooked bias sources. We rigorously validate the VAE-GMM model's performance...
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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...of fetal gene programs. Reactivation of these fetal programs has compensatory effects during heart failure, depending on the type and stage of the underlying cardiomyopathy. Thousands of putative cardiac gene regulatory elements have been identified that may control these programs, but their functions...
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